Kate Johnson
May 25, 2010 — A new Web site aimed at streamlining reporting and surveillance of safety and adverse events has been launched by the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH), the agencies announced yesterday.
"The portal will be a key detection tool in improving the country's nationwide surveillance system and will strengthen our ability to protect the nation's health," FDA Commissioner Margaret A. Hamburg said in a news release.
The Safety Reporting Portal is part of the FDA's MedWatch Plus initiative. Its initial focus is primarily FDA-regulated foods (except dietary supplements and infant formula), as well as animal drugs and food and human gene transfer clinical trials. The FDA's preexisting MedWatch program will continue to focus on drug and medical device safety and adverse event reporting.
"The two systems are very similar and, over time, will merge into 1 system," Patricia El-Hinnawy, a press officer with the FDA, told Medscape Medical News. The Safety Reporting Portal will eventually expand to allow for mandatory reporting of serious events related to dietary supplements, as well as other clinical trials and products. In the meantime, it redirects traffic relating to these issues to the appropriate reporting sites.
When fully developed, the Web site will provide a mechanism for industry, healthcare professionals, and consumers to report a broad range of both pre- and postmarketing information to the federal government.
"This is the first step toward a common electronic reporting system that will offer one-stop shopping, allowing an individual to file a single report to multiple agencies that may have an interest in the event," the FDA notes in a news release.
In addition, the portal is intended to enhance the government's surveillance capabilities. "We will now be able to analyze human and animal safety-related events more quickly and identify those measures needed to protect the public," Dr. Hamburg said.
For More information, click on the title of this news or cut/copy and paste the below link in new window
https://www.safetyreporting.hhs.gov/fpsr/WorkflowLoginIO.aspx?metinstance=02039412009E655E84A96E3B7082E4C0A352E60B
Source: Medscape
Saturday, May 29, 2010
Diet Free of Gluten and Casein Has No Effect on Autism Symptoms
By Daniel M. Keller, PhD
May 24, 2010 (Philadelphia, Pennsylvania) — A gluten-free, casein-free (GFCF) diet or challenges with these food substances did not alter sleep or activity patterns in preschool children with autism spectrum disorder (ASD) who were also receiving intense behavioral therapy, suggests the first study to control for nutritional sufficiency and other interventions.
Slight differences in social language, approach, and play that were seen at 2 hours after gluten or casein exposure were not apparent at 24 hours, lead author Susan Hyman, MD, chief of the Division of Neurodevelopmental and Behavioral Pediatrics and associate professor of pediatrics at the University of Rochester in New York, reported here at the 9th Annual International Meeting for Autism Research.
Although dietary interventions are often used with children with ASD, have a popular image among the public, and result in anecdotal reports of improvement, prior trials have not borne out such positive outcomes. Dr. Hyman explained that she and her colleagues therefore designed a study to test whether a commonly used dietary intervention was safe and effective.
Study Population Stable at Baseline
Researchers recruited 22 children (age, 30 - 54 months) who were very consistent in their clinical presentations (positive on the Autism Diagnostic Interview and the Autism Diagnostic Observation Schedule), their medical conditions, and the therapies they were receiving, which was an early intensive behavioral intervention program. "This is important because if you're changing other parameters, you want to have other effective treatments stable," Dr. Hyman said. Children were excluded from the study if they had celiac disease, food allergies, or deficient iron stores.
The investigators formulated and monitored a nutritionally sound, strict GFCF diet, which they maintained children on for a minimum of 4 weeks. A staff of dieticians worked with the families to identify a food that their child would eat and that could be formulated to be indistinguishable with or without the test ingredients.
Fourteen of the children were able to maintain the diet and allow data collection. They remained on the diet and were observed and then challenged with the food substances (20 g wheat flour, 20 g evaporated milk, both, or placebo) only if they were at their behavioral baselines. Challenges were administered in a randomized, double-blind fashion. Each child received a food challenge on 3 separate occasions over 12 weeks.
To ensure nutritional adequacy, laboratory monitoring, body mass index, weight, and growth recording occurred at baseline, 6, 8, and 30 weeks. The researchers also collected behavioral data at these times, as well as the day before and 2 and 24 hours after each food challenge.
No Difference in Activity Levels After Dietary Challenge
Dr. Hyman reported that there was no difference in the length of sleep recorded by parents over the course of the study before and after challenges and compared with baseline. There were also no changes in the number of night wakings or in the number or consistency of stools.
Compared with placebo challenges, no significant differences occurred in length of sleep or waking with gluten (P = .21 and P = .10, respectively), casein (P = .48 and P = .15, respectively), or both (P = .99 and P = .18, respectively). Similarly, there were no differences in stool consistency compared with placebo.
Children's activity levels recorded by parents, researchers, or applied behavior analysis program teachers did not differ after placebo, gluten, casein, or gluten/casein challenges. These observations were consistent with recordings from actigraphs — watch-like devices that measure activity.
Dr. Hyman noted that these measures are not specific to autism. Thus, the play-based Ritvo-Freeman Real Life Rating Scale for autism was used to gauge sensory motor behaviors, social approach, and language. "With correction for multiple comparisons, there was no difference with the challenges compared to placebo, and there was no difference with introduction of the diet," she said.
To see whether any individual responses were obscured by group statistics, the researchers examined the single subject data but did not identify any child with significant effects after dietary challenges or who had improvements in core features of autism during the trial.
In summary, Dr. Hyman said, "The data that we have do not demonstrate effect of the GFCF diet on the behaviors we measured." However, she said that study limitations include the study's small size and that all the included children were in an effective early intervention program (≥10 hours/week), were of similar age, and were all stabilized on a monitored diet. Furthermore, none of the children was iron- or vitamin D-deficient.
Dr. Hyman said a question remains whether any autistic children could respond to the diet used in the study. For example, children with celiac disease or bad gastrointestinal symptoms were not included. "So could it be that children who have more significant [gastrointestinal] symptoms are the ones that drive the anecdotal reports?" she asked. Another possibility is that foods designed to exclude gluten could also then lack food preservatives or dyes, which is another open question.
Dr. Hyman concluded, "The data that we have do not offer support for the [GFCF] diet in young children who carry a diagnosis of autism and who are receiving other effective behavioral and educational interventions." She cautioned that these data should not be extrapolated to any child with food allergies or intolerances or other gastrointestinal problems, and that "any child who is on the diet needs to be monitored from a nutritional standpoint to make certain that all of the things that we know about typical child development are monitored for."
Jonathan Green, MD, professor of child and adolescent psychiatry at the University of Manchester, United Kingdom, commented that "studies of dietary interventions like this are extremely difficult to do." He calls himself "an interventionist" and leads the Medical Research Council preschool autism communication trial, currently the largest intervention trial internationally in this subject area.
"The [University of Rochester] study is of significance even though sample size is really small, but they really took a lot of trouble to blind the dietary intervention, and that's the really difficult thing to do," he said. He also commended Dr. Hyman's rigor in recording even what she called "oops events," where the child got a bit of food that was not planned, such as a cookie from grandma.
Dr. Green said that although there are hundreds of foods and ingredients that could be tested, he thought that Dr. Hyman addressed well 2 of parents' concerns by testing gluten and casein. "She's done the right test. She's used the right kind of methodology, which is really difficult on a small group of kids, and her results are pretty clear," he said.
Addressing the possibility that an autistic child with a preexisting gut problem would feel better on a gluten-free diet, he warned, "That, however, does not mean it's having an effect on the autism itself, and that's the point of what Dr. Hyman did.... What she's suggesting is that the diet in itself doesn't have a specific effect on autism as such." He said this kind of information should reach parents, who should see that autism researchers take their concerns seriously, and who thus need to believe the science.
In Dr. Hyman's opinion, "The real future of autism treatment is going to be informed by science. It's going to be informed by what we really do know about the brain and the designer interventions," she said. "What we have now in terms of intervention is empiric observation."
Source: Medscape
May 24, 2010 (Philadelphia, Pennsylvania) — A gluten-free, casein-free (GFCF) diet or challenges with these food substances did not alter sleep or activity patterns in preschool children with autism spectrum disorder (ASD) who were also receiving intense behavioral therapy, suggests the first study to control for nutritional sufficiency and other interventions.
Slight differences in social language, approach, and play that were seen at 2 hours after gluten or casein exposure were not apparent at 24 hours, lead author Susan Hyman, MD, chief of the Division of Neurodevelopmental and Behavioral Pediatrics and associate professor of pediatrics at the University of Rochester in New York, reported here at the 9th Annual International Meeting for Autism Research.
Although dietary interventions are often used with children with ASD, have a popular image among the public, and result in anecdotal reports of improvement, prior trials have not borne out such positive outcomes. Dr. Hyman explained that she and her colleagues therefore designed a study to test whether a commonly used dietary intervention was safe and effective.
Study Population Stable at Baseline
Researchers recruited 22 children (age, 30 - 54 months) who were very consistent in their clinical presentations (positive on the Autism Diagnostic Interview and the Autism Diagnostic Observation Schedule), their medical conditions, and the therapies they were receiving, which was an early intensive behavioral intervention program. "This is important because if you're changing other parameters, you want to have other effective treatments stable," Dr. Hyman said. Children were excluded from the study if they had celiac disease, food allergies, or deficient iron stores.
The investigators formulated and monitored a nutritionally sound, strict GFCF diet, which they maintained children on for a minimum of 4 weeks. A staff of dieticians worked with the families to identify a food that their child would eat and that could be formulated to be indistinguishable with or without the test ingredients.
Fourteen of the children were able to maintain the diet and allow data collection. They remained on the diet and were observed and then challenged with the food substances (20 g wheat flour, 20 g evaporated milk, both, or placebo) only if they were at their behavioral baselines. Challenges were administered in a randomized, double-blind fashion. Each child received a food challenge on 3 separate occasions over 12 weeks.
To ensure nutritional adequacy, laboratory monitoring, body mass index, weight, and growth recording occurred at baseline, 6, 8, and 30 weeks. The researchers also collected behavioral data at these times, as well as the day before and 2 and 24 hours after each food challenge.
No Difference in Activity Levels After Dietary Challenge
Dr. Hyman reported that there was no difference in the length of sleep recorded by parents over the course of the study before and after challenges and compared with baseline. There were also no changes in the number of night wakings or in the number or consistency of stools.
Compared with placebo challenges, no significant differences occurred in length of sleep or waking with gluten (P = .21 and P = .10, respectively), casein (P = .48 and P = .15, respectively), or both (P = .99 and P = .18, respectively). Similarly, there were no differences in stool consistency compared with placebo.
Children's activity levels recorded by parents, researchers, or applied behavior analysis program teachers did not differ after placebo, gluten, casein, or gluten/casein challenges. These observations were consistent with recordings from actigraphs — watch-like devices that measure activity.
Dr. Hyman noted that these measures are not specific to autism. Thus, the play-based Ritvo-Freeman Real Life Rating Scale for autism was used to gauge sensory motor behaviors, social approach, and language. "With correction for multiple comparisons, there was no difference with the challenges compared to placebo, and there was no difference with introduction of the diet," she said.
To see whether any individual responses were obscured by group statistics, the researchers examined the single subject data but did not identify any child with significant effects after dietary challenges or who had improvements in core features of autism during the trial.
In summary, Dr. Hyman said, "The data that we have do not demonstrate effect of the GFCF diet on the behaviors we measured." However, she said that study limitations include the study's small size and that all the included children were in an effective early intervention program (≥10 hours/week), were of similar age, and were all stabilized on a monitored diet. Furthermore, none of the children was iron- or vitamin D-deficient.
Dr. Hyman said a question remains whether any autistic children could respond to the diet used in the study. For example, children with celiac disease or bad gastrointestinal symptoms were not included. "So could it be that children who have more significant [gastrointestinal] symptoms are the ones that drive the anecdotal reports?" she asked. Another possibility is that foods designed to exclude gluten could also then lack food preservatives or dyes, which is another open question.
Dr. Hyman concluded, "The data that we have do not offer support for the [GFCF] diet in young children who carry a diagnosis of autism and who are receiving other effective behavioral and educational interventions." She cautioned that these data should not be extrapolated to any child with food allergies or intolerances or other gastrointestinal problems, and that "any child who is on the diet needs to be monitored from a nutritional standpoint to make certain that all of the things that we know about typical child development are monitored for."
Jonathan Green, MD, professor of child and adolescent psychiatry at the University of Manchester, United Kingdom, commented that "studies of dietary interventions like this are extremely difficult to do." He calls himself "an interventionist" and leads the Medical Research Council preschool autism communication trial, currently the largest intervention trial internationally in this subject area.
"The [University of Rochester] study is of significance even though sample size is really small, but they really took a lot of trouble to blind the dietary intervention, and that's the really difficult thing to do," he said. He also commended Dr. Hyman's rigor in recording even what she called "oops events," where the child got a bit of food that was not planned, such as a cookie from grandma.
Dr. Green said that although there are hundreds of foods and ingredients that could be tested, he thought that Dr. Hyman addressed well 2 of parents' concerns by testing gluten and casein. "She's done the right test. She's used the right kind of methodology, which is really difficult on a small group of kids, and her results are pretty clear," he said.
Addressing the possibility that an autistic child with a preexisting gut problem would feel better on a gluten-free diet, he warned, "That, however, does not mean it's having an effect on the autism itself, and that's the point of what Dr. Hyman did.... What she's suggesting is that the diet in itself doesn't have a specific effect on autism as such." He said this kind of information should reach parents, who should see that autism researchers take their concerns seriously, and who thus need to believe the science.
In Dr. Hyman's opinion, "The real future of autism treatment is going to be informed by science. It's going to be informed by what we really do know about the brain and the designer interventions," she said. "What we have now in terms of intervention is empiric observation."
Source: Medscape
New Finding Adds Weight to Ketogenic Diet for Childhood Seizures
May 27, 2010 — The ketogenic diet is an effective alternative for pediatric patients with persistent seizures who have not responded to other therapies, say investigators. Reporting results from the largest analysis to date, researchers from Johns Hopkins Children's Center, Baltimore, Maryland, show that about two-thirds of refractory patients respond to the high-fat, low-carbohydrate diet.
"Stopping or reducing the number of seizures can go a long way toward preserving neurological function, and the ketogenic diet should be our immediate next line of defense in children with persistent infantile spasms who don’t improve with medication," senior investigator Eric Kossoff, MD, a pediatric neurologist and director of the ketogenic diet program at Hopkins, said in a news release.
The new study is a follow-up of a 2002 report that showed the diet worked well in a small number of children with infantile spasms. The current report, published online in Epilepsia, includes 104 pediatric patients.
The ketogenic diet provides just enough protein for body growth and repair and sufficient calories to maintain a healthy weight. The classic ketogenic diet contains a 4:1 ratio of fat to combined protein and carbohydrate.
"We have seen a significant increase in referrals for the ketogenic diet for intractable infantile spasms," note the study authors. They have also started using the diet in new-onset cases. "The purpose of this study was to use the increased patient cohort to evaluate for predictive factors for success, compare results over time, and evaluate long-term seizure, electroencephalogram, and developmental outcomes."
The researchers show that nearly 40% of children became seizure free for at least 6 months. Most of these have remained seizure free for at least 2 years.
Table. Spasm Reduction at Each Follow-up
Reduction,% 3 Months,% 6 Months,% 9 Months,% 1 Year,% 2 Years,%
Seizure free 18 28 32 30 33
>90 13 11 14 13 11
50–90 32 25 27 34 33
<50 37 36 27 23 23
The investigators also report significant improvements in development and electroencephalograms, as well as a reduction in the number of concurrent anticonvulsants.
The mean age of patients was 1.2 years. Previous therapy included on average 3.6 anticonvulsants. Most patients had tried corticosteroids or vigabatrin.
The researchers used the diet first line in 18 patients with newly diagnosed seizures never treated with drugs. Ten of these patients became seizure free within 2 weeks of starting the diet.
The finding suggests that in some children the diet may work well as first-line therapy. Debating at the American Epilepsy Society 63rd Annual Scientific Conference in December, experts weighed the pros and cons of this approach.
Speaker Elizabeth Donner, MD, from the Hospital for Sick Children in Toronto, Ontario, Canada, argued at the meeting that the ketogenic diet is effective and should be considered first line in infantile spasms and especially in GLUT1 and pyruvate dehydrogenase deficiency.
First Line In GLUT1 and Pyruvate Dehydrogenase Deficiency
"Antiepileptic drugs do bad things to children," Dr. Donner said, naming a long list of adverse effects — many serious and some involving cognitive impairment. "In some cases, antiepileptic drugs can even make seizures worse," she said.
Dr. Donner suggested that since the ketogenic diet works quickly, it makes sense to try it first line.
Speaker Douglas Nordli, MD, from the Children's Memorial Hospital in Chicago, Illinois, agreed the ketogenic diet can be used first line in patients with GLUT1 or pyruvate dehydrogenase deficiency. However, he argued there is otherwise limited evidence confirming the benefits of the diet.
Dr. Nordli says it is not easy for dieticians and families to start a ketogenic diet emergently, so he will continue to try 1 or 2 medications first.
"The diet is not completely innocuous," he added, noting that it can be especially dangerous for patients with underlying metabolic defects.
Common adverse effects include constipation, heartburn, diarrhea, behavior problems, kidney stones, and temporary spikes in cholesterol levels. In this study, adverse effects were observed in a third of children. Some also experienced diminished growth (6%).
"We would do a disservice to the ketogenic diet to propose it first line without sufficient prospective comparative data," Dr. Nordli said. "Articles showing a probable beneficial effect are not the same as comparative superiority to existing agents."
Speaking to Medscape Neurology, lead study author Amanda Hong, a medical student at Hopkins, said her team agrees. "Additional prospective, multicenter studies are needed."
This study was funded by Johns Hopkins University and the National Institutes of Health. Dr. Kossoff has received financial support from Nutricia Inc for unrelated research pertaining to their products.
Epilepsia. Published online April 30, 2010.
Source: Medscape
"Stopping or reducing the number of seizures can go a long way toward preserving neurological function, and the ketogenic diet should be our immediate next line of defense in children with persistent infantile spasms who don’t improve with medication," senior investigator Eric Kossoff, MD, a pediatric neurologist and director of the ketogenic diet program at Hopkins, said in a news release.
The new study is a follow-up of a 2002 report that showed the diet worked well in a small number of children with infantile spasms. The current report, published online in Epilepsia, includes 104 pediatric patients.
The ketogenic diet provides just enough protein for body growth and repair and sufficient calories to maintain a healthy weight. The classic ketogenic diet contains a 4:1 ratio of fat to combined protein and carbohydrate.
"We have seen a significant increase in referrals for the ketogenic diet for intractable infantile spasms," note the study authors. They have also started using the diet in new-onset cases. "The purpose of this study was to use the increased patient cohort to evaluate for predictive factors for success, compare results over time, and evaluate long-term seizure, electroencephalogram, and developmental outcomes."
The researchers show that nearly 40% of children became seizure free for at least 6 months. Most of these have remained seizure free for at least 2 years.
Table. Spasm Reduction at Each Follow-up
Reduction,% 3 Months,% 6 Months,% 9 Months,% 1 Year,% 2 Years,%
Seizure free 18 28 32 30 33
>90 13 11 14 13 11
50–90 32 25 27 34 33
<50 37 36 27 23 23
The investigators also report significant improvements in development and electroencephalograms, as well as a reduction in the number of concurrent anticonvulsants.
The mean age of patients was 1.2 years. Previous therapy included on average 3.6 anticonvulsants. Most patients had tried corticosteroids or vigabatrin.
The researchers used the diet first line in 18 patients with newly diagnosed seizures never treated with drugs. Ten of these patients became seizure free within 2 weeks of starting the diet.
The finding suggests that in some children the diet may work well as first-line therapy. Debating at the American Epilepsy Society 63rd Annual Scientific Conference in December, experts weighed the pros and cons of this approach.
Speaker Elizabeth Donner, MD, from the Hospital for Sick Children in Toronto, Ontario, Canada, argued at the meeting that the ketogenic diet is effective and should be considered first line in infantile spasms and especially in GLUT1 and pyruvate dehydrogenase deficiency.
First Line In GLUT1 and Pyruvate Dehydrogenase Deficiency
"Antiepileptic drugs do bad things to children," Dr. Donner said, naming a long list of adverse effects — many serious and some involving cognitive impairment. "In some cases, antiepileptic drugs can even make seizures worse," she said.
Dr. Donner suggested that since the ketogenic diet works quickly, it makes sense to try it first line.
Speaker Douglas Nordli, MD, from the Children's Memorial Hospital in Chicago, Illinois, agreed the ketogenic diet can be used first line in patients with GLUT1 or pyruvate dehydrogenase deficiency. However, he argued there is otherwise limited evidence confirming the benefits of the diet.
Dr. Nordli says it is not easy for dieticians and families to start a ketogenic diet emergently, so he will continue to try 1 or 2 medications first.
"The diet is not completely innocuous," he added, noting that it can be especially dangerous for patients with underlying metabolic defects.
Common adverse effects include constipation, heartburn, diarrhea, behavior problems, kidney stones, and temporary spikes in cholesterol levels. In this study, adverse effects were observed in a third of children. Some also experienced diminished growth (6%).
"We would do a disservice to the ketogenic diet to propose it first line without sufficient prospective comparative data," Dr. Nordli said. "Articles showing a probable beneficial effect are not the same as comparative superiority to existing agents."
Speaking to Medscape Neurology, lead study author Amanda Hong, a medical student at Hopkins, said her team agrees. "Additional prospective, multicenter studies are needed."
This study was funded by Johns Hopkins University and the National Institutes of Health. Dr. Kossoff has received financial support from Nutricia Inc for unrelated research pertaining to their products.
Epilepsia. Published online April 30, 2010.
Source: Medscape
Friday, May 28, 2010
Rett syndrome research Trust: Of Mice and Men…Or in the Case of Rett…Of Mice and Women
Anyone who keeps up with Rett research knows that the different mouse models of the disease have given us a rich knowledge base. But have you ever stopped to think of how scientists get access to these crucial models? Today we share with you a conversation between Cathleen Lutz of The Jackson Laboratory in Bar Harbor, Maine, and Monica Coenraads, Executive Director of the Rett Syndrome Research Trust. Jackson is the gold standard for the colonization and distribution of mouse models of disease.
MC: Thank you, Dr. Lutz, for spending some time with us. Tell us a bit about the background behind Jackson Laboratories.
CL: Jackson Laboratories was established by Clarence Cooks Little and Roscoe B. Jackson in 1929 as a genetics institute. Financial support came from Detroit industrialists such as Edsel Ford and Roscoe Jackson, president of the Hudson Motorcar Company, with land donated by family friend George B. Dorr. Of course, Bar Harbor has a long history of philanthropic summer residents who supported the Laboratory, for example the Rockefellers had settled on Bar Harbor.
Off the coast of Maine may seem like a strange place to have a genetics facility. The advantage to the location is that at the time there wasn’t any air conditioning, so the ocean breezes really kept the animal facilities cool. In the early years we didn’t have the ability to do genetic engineering, so essentially we relied on spontaneous mutations that resulted in interesting things to study.
MC: I’ve recently learned of veterinary schools setting up facilities to diagnose animals with spontaneous genetic mutations. For example, it’s possible that a dog with a mutation in MECP2 would be taken to vet and a bright geneticist might be able to diagnose the animal. This would allow different species to be studied without having to do all the expensive and time consuming genetic engineering involved with making models.
CL: In fact I just attended a seminar on this. Recently a naturally occurring form of ALS was identified in dogs. What is particularly interesting is that the canine form of ALS progresses slowly, unlike the human ALS where patients usually die within 5 years of diagnosis. The key question is what is genetically protecting these dogs?
MC: The hope is that genetic modifiers are protecting these dogs from their mutations in SOD1, an ALS gene. And if you can identify these modifiers it may open up avenues for intervention. We have the same situation in Rett. Currently RSRT is funding a project in the lab of Monica Justice at Baylor to look for genetic modifiers in the Rett mice models.
How many disease models would you estimate that Jackson has?
CL: We have over 5000 different strains here at the Jackson Laboratory.
MC: How many new strains are imported every year?
CL: We’re importing about 600 new strains every year.
MC: Is Jackson struggling to keep up given such large numbers?
CL: We have over 1300 strains live on the shelf and over the years have worked to meticulously manage the supply and demand of the strains so investigators can get a jump start on their experiments. We also scale up our colony sizes for individual investigators who need a larger supply of animals than we currently may have. For strains that have low demand, those mice are available from our cryopreserved stocks. Cryopreservation involves either freezing embryos or sperm. Dr. Robert Taft at Jackson has been on the cutting edge of that technology and recently published his technique that helps recover sperm much more easily. Animals can then be recovered from cryopreserved stocks as needed.
So instead of having to super ovulate 50 or 60 females, fertilize, and bring embryos to the two cell stage for cryopreservation, all we have to do is take two males and freeze down the sperm and that particular model is completely archived. We cut down on shelf space and cost.
MC: When a laboratory needs a particular strain which is cryopreserved, that means you don’t have a live colony; what do you actually send them?
CL: It depends on where the requesting laboratory is physically located and the level of their expertise. Cryopreservation is still a rather novel technology so some labs are not equipped to handle the technique of thawing sperm and doing in vitro fertilization (IVF). In those cases we can take the sperm, thaw it and do an IVF to donor females and then we’ll send them live mice. Alternatively we can send frozen viable embryos. This works well especially if the lab is an international customer because we have all kinds of handcuffs regarding transportation of live animals and tissues outside the country.
MC: How many scientists do you estimate have purchased from Jackson?
CL: Last year over 19,000 investigators from 50 countries purchased 2.7 million mice.
MC: That is unbelievable! How is Jackson funded?
CL: We are a not for profit organization with three prongs. We are a research organization; a resource organization, that’s the mouse distribution portion of our institution; and we run courses and conferences where we teach people the latest technologies.
Most of the research and courses are funded mainly through NIH grants. A large portion of our Mouse Repository is also funded through NIH program grants. The rest of the funding required for running the Repository comes from the fees we charge for the mice we distribute. The proceeds go right back into the operation to acquire more mice and outfit new facilities to expand the program. It’s very expensive to distribute mice because we have to maintain high health standards so that any institutions can receive mice knowing that they are free of viruses and pathogens that could contaminate their facility. We also have philanthropic donations.
MC: When I was the Director of Research at the Rett Syndrome Research Foundation we financially supported the importation and colonization of several Rett animal models at Jackson. That was money very well spent as those mice have now been distributed to hundreds of labs and have formed the foundation of much of what we have learned about Rett Syndrome.
You shared that in 2009, 95 different labs ordered Rett mice. The first Rett mouse model made by Adrian Bird was published in 2001, so Jackson had it ready for purchase in 2002. So eight years later almost 100 researchers bought this mouse.
CL: Yes, there is still a lot of demand for that animal, partly because it’s one of the better models of neurological disease. But it’s always going to take more than one model to really dissect what it is that you’re looking for. So if you want to ask specific questions it’s very helpful to be able to utilize more than one type of mouse model. So one model may have a point mutation, another may have a complete exon deleted, yet another may be a conditional mutation so you can just make that mouse gene defective in certain tissues and not others. When you put the collection all together it makes for a really good research resource…your toolbox, so to speak.
MC: I want to acknowledge the scientists who have developed the Rett mouse models: Adrian Bird, Rudolf Jaenisch and Huda Zoghbi. All of them quickly deposited their mice with either Jackson or the Mutant Mouse Regional Resource Center, thereby giving the research community at large access to the mice. This type of sharing does not always happen and I’m so grateful that they set a high standard for our community in terms of accessibility to these models. I hope that it’s a standard that others will follow.
MC: The recent ability to manipulate rat embryonic cells now makes it possible to create rat models of genetic disease. Does Jackson plan to expand into rat models?
CL: We’ve really talked about it a lot as genetic engineering in rats has come a long way in the last few years. One problem is that sperm cryopreservation in rats is still not as efficient as it is in mice. And the housing of rats is so much more expensive because they are so much bigger than mice.
So we have to realize analyze what the advantages of working in rats versus mice are.
MC: Rats are considered smarter than mice.
CL: Yes, they are. They are probably a better model for studying behavior, as well as learning and memory, which will be important in many neurological diseases. But the advantages of studying diabetes in a rat versus mice, for example, is less clear. There is a rat repository in Missouri run by John Critser. I think that Jackson will basically rely on the Missouri repository, working with them when and if needed.. But certainly we’d like to see the cryopreservation and the sperm recovery be just as easy and cost effective and efficient for rats as it is for mice so that we could we could cut the cost and make the process feasible.
MC: I wonder then how many labs would purchase rats. It would be a big learning curve to switch and the costs would be so much higher.
CL: Yes. That’s absolutely true. So there again I think researchers will really need to ask themselves what the advantage to using rats is for their particular research.
MC: Jackson also does its own research and has some high profile scientists on staff.
CL: We have 35 staff scientists on site working right now in a variety of areas. We have cancer biologists, neuroscientists, bioinformaticians. We have investigators who specialize in metabolic diseases like diabetes and obesity. We try to be as diverse as we possibly can in that respect.
MC: And why do you think the scientists would choose to work at Jackson and not at an academic institution?
CL: There are many factors but I think one of the attractions is the availability on site of all of the different mouse models. Also the sheer size of our operation means we can offer economies of scale. The per diem costs of mouse experiments are much lower than they would be at other institutions. That is a very attractive feature for scientists. If researchers need large numbers for their studies then this is the place to do it.
MC: Is there anything you would like to say to families of children with Rett Syndrome?
CL: I’d Iike to let people know that our mission at the Jackson Laboratories is really for the families, for the patients, and for biomedical research. We have, as I described, the repository and the disease model resources. It is quite an undertaking and we really feel that it is within our scientific mission to be collecting these animals and to be making them as readily available to the scientific community as we possibly can. That’s why we’re here and we feel that over the years we’ve really developed the expertise to do that and to manage the sheer numbers of strains that we have live on the shelf.
MC: Jackson truly provides an important resource for the scientific community. Thank you, Dr. Lutz, for sharing some of your knowledge with us today.
Source: Rett syndrome research trust
MC: Thank you, Dr. Lutz, for spending some time with us. Tell us a bit about the background behind Jackson Laboratories.
CL: Jackson Laboratories was established by Clarence Cooks Little and Roscoe B. Jackson in 1929 as a genetics institute. Financial support came from Detroit industrialists such as Edsel Ford and Roscoe Jackson, president of the Hudson Motorcar Company, with land donated by family friend George B. Dorr. Of course, Bar Harbor has a long history of philanthropic summer residents who supported the Laboratory, for example the Rockefellers had settled on Bar Harbor.
Off the coast of Maine may seem like a strange place to have a genetics facility. The advantage to the location is that at the time there wasn’t any air conditioning, so the ocean breezes really kept the animal facilities cool. In the early years we didn’t have the ability to do genetic engineering, so essentially we relied on spontaneous mutations that resulted in interesting things to study.
MC: I’ve recently learned of veterinary schools setting up facilities to diagnose animals with spontaneous genetic mutations. For example, it’s possible that a dog with a mutation in MECP2 would be taken to vet and a bright geneticist might be able to diagnose the animal. This would allow different species to be studied without having to do all the expensive and time consuming genetic engineering involved with making models.
CL: In fact I just attended a seminar on this. Recently a naturally occurring form of ALS was identified in dogs. What is particularly interesting is that the canine form of ALS progresses slowly, unlike the human ALS where patients usually die within 5 years of diagnosis. The key question is what is genetically protecting these dogs?
MC: The hope is that genetic modifiers are protecting these dogs from their mutations in SOD1, an ALS gene. And if you can identify these modifiers it may open up avenues for intervention. We have the same situation in Rett. Currently RSRT is funding a project in the lab of Monica Justice at Baylor to look for genetic modifiers in the Rett mice models.
How many disease models would you estimate that Jackson has?
CL: We have over 5000 different strains here at the Jackson Laboratory.
MC: How many new strains are imported every year?
CL: We’re importing about 600 new strains every year.
MC: Is Jackson struggling to keep up given such large numbers?
CL: We have over 1300 strains live on the shelf and over the years have worked to meticulously manage the supply and demand of the strains so investigators can get a jump start on their experiments. We also scale up our colony sizes for individual investigators who need a larger supply of animals than we currently may have. For strains that have low demand, those mice are available from our cryopreserved stocks. Cryopreservation involves either freezing embryos or sperm. Dr. Robert Taft at Jackson has been on the cutting edge of that technology and recently published his technique that helps recover sperm much more easily. Animals can then be recovered from cryopreserved stocks as needed.
So instead of having to super ovulate 50 or 60 females, fertilize, and bring embryos to the two cell stage for cryopreservation, all we have to do is take two males and freeze down the sperm and that particular model is completely archived. We cut down on shelf space and cost.
MC: When a laboratory needs a particular strain which is cryopreserved, that means you don’t have a live colony; what do you actually send them?
CL: It depends on where the requesting laboratory is physically located and the level of their expertise. Cryopreservation is still a rather novel technology so some labs are not equipped to handle the technique of thawing sperm and doing in vitro fertilization (IVF). In those cases we can take the sperm, thaw it and do an IVF to donor females and then we’ll send them live mice. Alternatively we can send frozen viable embryos. This works well especially if the lab is an international customer because we have all kinds of handcuffs regarding transportation of live animals and tissues outside the country.
MC: How many scientists do you estimate have purchased from Jackson?
CL: Last year over 19,000 investigators from 50 countries purchased 2.7 million mice.
MC: That is unbelievable! How is Jackson funded?
CL: We are a not for profit organization with three prongs. We are a research organization; a resource organization, that’s the mouse distribution portion of our institution; and we run courses and conferences where we teach people the latest technologies.
Most of the research and courses are funded mainly through NIH grants. A large portion of our Mouse Repository is also funded through NIH program grants. The rest of the funding required for running the Repository comes from the fees we charge for the mice we distribute. The proceeds go right back into the operation to acquire more mice and outfit new facilities to expand the program. It’s very expensive to distribute mice because we have to maintain high health standards so that any institutions can receive mice knowing that they are free of viruses and pathogens that could contaminate their facility. We also have philanthropic donations.
MC: When I was the Director of Research at the Rett Syndrome Research Foundation we financially supported the importation and colonization of several Rett animal models at Jackson. That was money very well spent as those mice have now been distributed to hundreds of labs and have formed the foundation of much of what we have learned about Rett Syndrome.
You shared that in 2009, 95 different labs ordered Rett mice. The first Rett mouse model made by Adrian Bird was published in 2001, so Jackson had it ready for purchase in 2002. So eight years later almost 100 researchers bought this mouse.
CL: Yes, there is still a lot of demand for that animal, partly because it’s one of the better models of neurological disease. But it’s always going to take more than one model to really dissect what it is that you’re looking for. So if you want to ask specific questions it’s very helpful to be able to utilize more than one type of mouse model. So one model may have a point mutation, another may have a complete exon deleted, yet another may be a conditional mutation so you can just make that mouse gene defective in certain tissues and not others. When you put the collection all together it makes for a really good research resource…your toolbox, so to speak.
MC: I want to acknowledge the scientists who have developed the Rett mouse models: Adrian Bird, Rudolf Jaenisch and Huda Zoghbi. All of them quickly deposited their mice with either Jackson or the Mutant Mouse Regional Resource Center, thereby giving the research community at large access to the mice. This type of sharing does not always happen and I’m so grateful that they set a high standard for our community in terms of accessibility to these models. I hope that it’s a standard that others will follow.
MC: The recent ability to manipulate rat embryonic cells now makes it possible to create rat models of genetic disease. Does Jackson plan to expand into rat models?
CL: We’ve really talked about it a lot as genetic engineering in rats has come a long way in the last few years. One problem is that sperm cryopreservation in rats is still not as efficient as it is in mice. And the housing of rats is so much more expensive because they are so much bigger than mice.
So we have to realize analyze what the advantages of working in rats versus mice are.
MC: Rats are considered smarter than mice.
CL: Yes, they are. They are probably a better model for studying behavior, as well as learning and memory, which will be important in many neurological diseases. But the advantages of studying diabetes in a rat versus mice, for example, is less clear. There is a rat repository in Missouri run by John Critser. I think that Jackson will basically rely on the Missouri repository, working with them when and if needed.. But certainly we’d like to see the cryopreservation and the sperm recovery be just as easy and cost effective and efficient for rats as it is for mice so that we could we could cut the cost and make the process feasible.
MC: I wonder then how many labs would purchase rats. It would be a big learning curve to switch and the costs would be so much higher.
CL: Yes. That’s absolutely true. So there again I think researchers will really need to ask themselves what the advantage to using rats is for their particular research.
MC: Jackson also does its own research and has some high profile scientists on staff.
CL: We have 35 staff scientists on site working right now in a variety of areas. We have cancer biologists, neuroscientists, bioinformaticians. We have investigators who specialize in metabolic diseases like diabetes and obesity. We try to be as diverse as we possibly can in that respect.
MC: And why do you think the scientists would choose to work at Jackson and not at an academic institution?
CL: There are many factors but I think one of the attractions is the availability on site of all of the different mouse models. Also the sheer size of our operation means we can offer economies of scale. The per diem costs of mouse experiments are much lower than they would be at other institutions. That is a very attractive feature for scientists. If researchers need large numbers for their studies then this is the place to do it.
MC: Is there anything you would like to say to families of children with Rett Syndrome?
CL: I’d Iike to let people know that our mission at the Jackson Laboratories is really for the families, for the patients, and for biomedical research. We have, as I described, the repository and the disease model resources. It is quite an undertaking and we really feel that it is within our scientific mission to be collecting these animals and to be making them as readily available to the scientific community as we possibly can. That’s why we’re here and we feel that over the years we’ve really developed the expertise to do that and to manage the sheer numbers of strains that we have live on the shelf.
MC: Jackson truly provides an important resource for the scientific community. Thank you, Dr. Lutz, for sharing some of your knowledge with us today.
Source: Rett syndrome research trust
Sunday, May 23, 2010
Beat Autism Now.........
Dr. Michael A. Gruttadauria is the father of two children diagnosed with Autistic Spectrum Disorders.
Over 6 years ago, after being told of his first child's' diagnosis, he set out to find a way to increase brain functionality in children on the spectrum. He spent literally thousands of hours researching the research and what he found was truly startling.
In 2006, Dr. Mike opened the facility called the L.I. Spectrum Center in Plainview, NY., and now he helps people worldwide with his new book, Beat Autism Now!
Read full article by clicking on the Title Link..........
Source: BEAT AUTISM NOW
Over 6 years ago, after being told of his first child's' diagnosis, he set out to find a way to increase brain functionality in children on the spectrum. He spent literally thousands of hours researching the research and what he found was truly startling.
In 2006, Dr. Mike opened the facility called the L.I. Spectrum Center in Plainview, NY., and now he helps people worldwide with his new book, Beat Autism Now!
Read full article by clicking on the Title Link..........
Source: BEAT AUTISM NOW
Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome
A great discovery by Dr J. Craig Venter, promising the cure of all diseases in near future.
Source: NEWSWEEK
Source: NEWSWEEK
How the road from promising scientific breakthrough to real-world remedy has become all but a dead end.
From 1996 to 1999, the U.S. food and Drug Administration approved 157 new drugs. In the comparable period a decade later—that is, from 2006 to 2009—the agency approved 74. Not among them were any cures, or even meaningfully effective treatments, for Alzheimer's disease, lung or pancreatic cancer, Parkinson's disease, Huntington's disease, or a host of other afflictions that destroy lives.
Also not among the new drugs approved was A5G27, or whatever more mellifluous name a drug company might give it. In 2004 Hynda Kleinman and her colleagues at the National Institutes of Health discovered that this molecule, called a peptide, blocks the metastasis of melanoma to the lungs and other organs, at least in lab animals. The peptide also blocks angiogenesis, the creation of blood vessels that sustain metastatic tumors, they reported six years ago in the journal Cancer Research. Unfortunately, A5G27 has not been developed beyond that discovery. Kleinman was working at NIH's dental-research institute, and, she says, "there was not a lot of support for work in cancer there at the time. They weren't interested." She did not have the expertise to develop the peptide herself. "I continued doing cancer research on it, but I couldn't take it to the next level because I'm not a cancer specialist," she says. "I was trained as a chemist."
No one is saying A5G27 would have cured metastatic cancers, which account for some 90 percent of all cancer deaths; the chance of FDA approval for a newly discovered molecule, targeting a newly discovered disease mechanism, is a dismal 0.6 percent. Diseases are complicated, and nature fights every human attempt to mess with what she has wrought. But frustration is growing with how few seemingly promising discoveries in basic biomedical science lead to something that helps patients, especially in what is supposed to be a golden age of genetics, neuroscience, and biomedical research in general.
From 1998 to 2003, the budget of the NIH—which supports such research at universities and medical centers as well as within its own labs in Bethesda, Md.—doubled, to $27 billion, and is now $31 billion. There is very little downside, for a president or Congress, in appeasing patient-advocacy groups as well as voters by supporting biomedical research. But judging by the only criterion that matters to patients and taxpayers—not how many interesting discoveries about cells or genes or synapses have been made, but how many treatments for diseases the money has bought—the return on investment to the American taxpayer has been approximately as satisfying as the AIG bailout. "Basic research is healthy in America," says John Adler, a Stanford University professor who invented the CyberKnife, a robotic device that treats cancer with precise, high doses of radiation. "But patients aren't benefiting. Our understanding of diseases is greater than ever. But academics think, 'We had three papers in Science or Nature, so that must have been [NIH] money well spent.'?"
More and more policymakers and patients are therefore asking, where are the cures? The answer is that potential cures, or at least treatments, are stuck in the chasm between a scientific discovery and the doctor's office: what's been called the valley of death.
The barriers to exploiting fundamental discoveries begin with science labs themselves. In academia and the NIH, the system of honors, grants, and tenure rewards basic discoveries (a gene for Parkinson's! a molecule that halts metastasis!), not the grunt work that turns such breakthroughs into drugs. "Colleagues tell me they're very successful getting NIH grants because their experiments are elegant and likely to yield fundamental discoveries, even if they have no prospect of producing something that helps human diseases," says cancer biologist Raymond Hohl of the University of Iowa. In 2000, for instance, scientists at four separate labs discovered a gene called ABCC6, which, when mutated, causes PXE (pseudoxanthoma elasticum), a rare genetic disease in which the skin, eyes, heart, and other soft tissue become calcified—rock hard. By 2005, scientists had genetically engineered lab mice to develop the disease. The next step would be what's called screening, in which scientists would laboriously test one molecule after another to see which had any effect on ABCC6. But "academic scientists aren't capable of creating assays [test systems] to do that," says Sharon Terry, CEO of the Genetic Alliance, which supports research on rare genetic diseases (her children have PXE). "It's time-consuming drudgery and takes an expertise that hasn't trickled down to the typical academic scientist." Ten years later, there is still no cure for PXE.
Should a lab be so fortunate as to discover a molecule that cures a disease in a lab rat, the next step is to test its toxicity and efficacy in more lab animals. Without that, no company—for companies, not academic scientists, actually develop drugs—will consider buying the rights to it. "A company wants to know, how specific and toxic is the molecule?" says Kenneth Chahine, an expert in patent law at the University of Utah. "It might work great in a mouse, but will it make a rat keel over? Doing this less fun research is not something an academic lab is interested in. The incentive driving academic labs is grants for creative, innovative research, and you're not going to get one to learn how much of a compound kills a rat."
How this culture works against finding treatments can be seen in Huntington's disease, a single-gene, fatal illness. "We have something like 300 targets [genes, pathways, and other mechanisms thought to cause the disease] and almost as many theories," says an official at a disease foundation, who asked not to be identified so as not to anger scientists he has to work with. "The way science careers are structured, big labs get established based on a theory or a target or a mechanism, and the last thing they want to do is disprove it and give up what they're working on. That's why we have so many targets. We'd like people to work on moving them from a 'maybe' to a 'no,' but it's bad for careers to rule things out: that kind of study tends not to get published, so doing that doesn't advance people's careers."
For scientists who are willing to push past these obstacles, the next one is the patent system. When Robert Sackstein was a bone-marrow-transplant surgeon in the 1980s, he noticed that fewer than 5 percent of the transplanted blood stem cells reached their target in a patient's marrow. He therefore decided to study how cells navigate, what beacons they follow. A decade-long search led to the discovery of a molecule on the surface of blood stem cells that turns out to be the master molecule used by those cells to home in on any site in the body.
Sackstein named the molecule HCELL. If stem cells were tagged with HCELL, he thought, they would make a beeline for the correct tissue—say, to regenerate bones in patients with osteoporosis. In 2008 he and colleagues announced in a paper in Nature Medicine that they had managed to do just that: when he injected human bone-forming stem cells tagged with HCELL into mice, the cells headed for the mice's bones and began forming human bone there. HCELL-tagged stem cells, in other words, could be the long-sought cure for osteoporosis, as well as other diseases that might be treatable with stem cells.
But because Sackstein had described HCELL in a scientific paper, the U.S. patent office told him it was rejecting his application. Ten years of appeals have cost hundreds of thousands of dollars in attorney fees. Sackstein fervently believes his discovery deserves a patent, and it was granted one in Europe and Japan. "You have to persevere," he says. "I can't let it go, because I think the impact on patients could be so great. We've cured osteoporosis in mice." But without patent protection, no company will develop HCELL for people, even in Europe or Japan. For a multinational drug company to go forward, it needs patent protection in the U.S. as well.
If a discovery is patented, the next step is for the university or NIH technology licensing office to find a commercial partner to develop its professors' discoveries. (The institution where a scientist works, not the scientist herself, owns the intellectual-property rights to discoveries, and thus the exclusive right to license it.) Licensing typically involves upfront fees, plus a promised share of royalties should the molecule become a commercial drug. One biotech startup in the Midwest has been trying for three years to license a discovery made when some of its founders worked at the NIH. Vascular surgeon Jeffrey Isenberg, now at the University of Pittsburgh Medical Center, and colleagues were studying how the gas nitric oxide promotes blood flow. They discovered a pathway that inhibits nitric oxide and thus impedes blood flow. By blocking the blocker—to football fans, adding an extra guard to your offensive line—the scientists got nitric oxide to open blood vessels again and increase blood flow, at least in lab animals. The molecule that works this magic is a protein called thrombospondin-1, or TSP1, suggesting that this particular offensive guard might be a potent drug for saving heart-attack victims; restoring blood flow in patients with severe diabetes, in which impaired blood flow leads to gangrene; and treating hypertension.
Unfortunately, attempts to negotiate the rights to develop this discovery were Kafkaesque. NIH's licensing office demanded payments that the startup—which, unlike the Pfizers of the world, has zero revenue—couldn't make. "NIH has no skin in the game, so they have no inducement to work with a company" to get a discovery from the lab to patients, says Eric Gulve, president of BioGenerator, a nonprofit in St. Louis that advises and provides seed money for biotech startups. "There isn't a sense of urgency." A top lab chief at the NIH laments that when scientists like himself push the licensing office to move a discovery toward commercialization, "it's just another piece of paper to them." Without the license, the startup struggles to stay alive. In its defense, Mark Rohrbaugh, the director of NIH's technology-transfer office, notes that it licensed 215 discoveries last year (though that is down from the 2004–2008 average of 273 a year, with a high of 313 in 2005). "I think we do incredibly well accommodating the needs of a company," says Rohrbaugh. "We have even linked milestone payments [made when a company achieves a goal such as starting a clinical trial] to a company raising money. The last thing we want to do is slow down the science."
If a discovery is licensed, the licensee then has to raise enough money to test the compound's toxicity (does it kill the lab rats? give them seizures?), to figure out how to make it in quantity and with uniform quality, to test the drug in larger lab animals such as dogs, and then to test it in people. Because large drug companies have been merging and retrenching (the industry laid off 90,000 people last year) and have become more interested in buying early-stage research than in doing it themselves, this role has been falling to biotech firms, which are smaller and poorer. It is at this step—turning a discovery into something that can be manufactured and that is safe and effective—that the valley of death has gotten dramatically more fatal over the last few years. "NIH grants don't support the kind of research needed to turn a discovery into a drug," says Gulve, so the money has to come from elsewhere. Traditionally, that has been venture capital. But "over the last four or five years VC funding for early-stage drug discovery has decreased dramatically," says Utah's Chahine. "You used to be able to go public, raising millions of dollars, based on a couple of genes in a rat. Now you can't even get a venture capitalist's business card for that."
Instead, VCs—essentially the only source of money to move preliminary discoveries forward—are demanding that startups prove themselves far more than in the past. Francis "Duke" Creighton had a eureka moment a few years ago: use magnets to amplify the effects of drugs that dissolve stroke-causing clots. He founded Pulse Therapeutics to develop the discovery, in which tiny magnetic particles would be mixed with a clot-busting drug, and a magnet would be used to get more of the drug to its target. He had enough money to do experiments for six months in vitro, "then we ran out," says Creighton. "Venture-capital firms said, 'Show me animal data and we'll talk,' but running animal experiments would cost $300,000 at the least." No money, no animal studies; no animal studies, no money. BioGenerator helped Creighton raise $100,000, but he's still short of what he needs.
Human testing is even more expensive—tens of millions of dollars—so commercial calculations stalk the decision like Banquo's ghost. Research funded by the Multiple Myeloma Re--search Foundation at a small biotech led to a promising new drug for multiple myeloma, a cancer of plasma cells in bones. But the firm was bought by a large drug company that decided against testing the drug in that cancer, calculating that the payoff would be greater if it could be shown to work against the big four (breast, lung, prostate, colon) or leukemias. "It's our feeling that if it had been tested in myeloma only, it would have moved faster," says Louise Perkins, chief scientific officer of the foundation.
If we are serious about rescuing potential new drugs from the valley of death, then academia, the NIH, and disease foundations will have to change how they operate. That is happening, albeit slowly. Private foundations such as the MMRF, the Michael J. Fox Foundation for Parkinson's Research, and the Myelin Repair Foundation (for multiple sclerosis) have veered away from the NIH model of "here's some money; go discover something." Instead, they are managing and directing scientists more closely, requiring them to share data before it is published, cooperate, and do the nonsexy development work required after a discovery is made.
For instance, the Chordoma Foundation, which supports research into that rare cancer, found that there was only one decent chordoma cell line in the whole world—in a freezer in Germany—and it hadn't been used for new research since 2001. The foundation obtained the legal rights to it and distributed it to some two dozen researchers, jump-starting studies that otherwise would never have been done. The cell line is being used to, among other things, screen existing drugs to see if they might work against chordoma.
Forcing that kind of cooperation among turf-jealous academics could break a lot of logjams. "There are thousands of researchers working on exactly the same thing," says Bruce Bloom, whose Partnership for Cures foundation supports research on new uses for existing drugs. "Under the current system they cannot and will not collaborate for fear that it will jeopardize funding, patent protection, and publication. Look at the progress open-source software has made in IT. Imagine the progress open-source research could make in biomedicine."
Perhaps the greatest sea change is that "more academics are starting to ask, 'How can I get funding to turn this discovery into something?' so universities are encouraging the creation of drug-development groups," says Jeff Ives, president of Satori Pharmaceuticals, a biotech in Cambridge, Mass., that is searching for Alzheimer's drugs. "The ivory-tower separation from the real world isn't acceptable anymore."
Stanford Medical School realized that. Although the NIH has increased support for research intended to help patients, points out Daria Mochly-Rosen of Stanford, there is still very little funding for steps such as testing a compound's toxicity in several species of lab animals, synthesizing the molecule, and scaling up that synthesis. "What we lack in academia is an understanding that these steps can be intellectually interesting, too," says Mochly-Rosen. To foster that, she founded Spark four years ago. It scrutinizes discoveries from Stanford scientists that have not been licensed to a company and, with industry input, identifies 20 per year that have promise. The inventor is taught the basics of drug development and gets funding support to carry out the "drudgery."
In perhaps the clearest sign that patience among even the staunchest supporters of biomedical research is running thin, the health-care-reform bill that became law in March includes a Cures Ac-celeration Network that Sen. Arlen Specter, a longtime supporter of biomedical research, sponsored. Located at the NIH, the network would give grants ($500 million is authorized this year) to biotech companies, academic researchers, and advocacy groups to help promising discoveries cross the valley of death. It may or may not make a difference. But something had better, and soon.
Source: NEWSWEEK
Also not among the new drugs approved was A5G27, or whatever more mellifluous name a drug company might give it. In 2004 Hynda Kleinman and her colleagues at the National Institutes of Health discovered that this molecule, called a peptide, blocks the metastasis of melanoma to the lungs and other organs, at least in lab animals. The peptide also blocks angiogenesis, the creation of blood vessels that sustain metastatic tumors, they reported six years ago in the journal Cancer Research. Unfortunately, A5G27 has not been developed beyond that discovery. Kleinman was working at NIH's dental-research institute, and, she says, "there was not a lot of support for work in cancer there at the time. They weren't interested." She did not have the expertise to develop the peptide herself. "I continued doing cancer research on it, but I couldn't take it to the next level because I'm not a cancer specialist," she says. "I was trained as a chemist."
No one is saying A5G27 would have cured metastatic cancers, which account for some 90 percent of all cancer deaths; the chance of FDA approval for a newly discovered molecule, targeting a newly discovered disease mechanism, is a dismal 0.6 percent. Diseases are complicated, and nature fights every human attempt to mess with what she has wrought. But frustration is growing with how few seemingly promising discoveries in basic biomedical science lead to something that helps patients, especially in what is supposed to be a golden age of genetics, neuroscience, and biomedical research in general.
From 1998 to 2003, the budget of the NIH—which supports such research at universities and medical centers as well as within its own labs in Bethesda, Md.—doubled, to $27 billion, and is now $31 billion. There is very little downside, for a president or Congress, in appeasing patient-advocacy groups as well as voters by supporting biomedical research. But judging by the only criterion that matters to patients and taxpayers—not how many interesting discoveries about cells or genes or synapses have been made, but how many treatments for diseases the money has bought—the return on investment to the American taxpayer has been approximately as satisfying as the AIG bailout. "Basic research is healthy in America," says John Adler, a Stanford University professor who invented the CyberKnife, a robotic device that treats cancer with precise, high doses of radiation. "But patients aren't benefiting. Our understanding of diseases is greater than ever. But academics think, 'We had three papers in Science or Nature, so that must have been [NIH] money well spent.'?"
More and more policymakers and patients are therefore asking, where are the cures? The answer is that potential cures, or at least treatments, are stuck in the chasm between a scientific discovery and the doctor's office: what's been called the valley of death.
The barriers to exploiting fundamental discoveries begin with science labs themselves. In academia and the NIH, the system of honors, grants, and tenure rewards basic discoveries (a gene for Parkinson's! a molecule that halts metastasis!), not the grunt work that turns such breakthroughs into drugs. "Colleagues tell me they're very successful getting NIH grants because their experiments are elegant and likely to yield fundamental discoveries, even if they have no prospect of producing something that helps human diseases," says cancer biologist Raymond Hohl of the University of Iowa. In 2000, for instance, scientists at four separate labs discovered a gene called ABCC6, which, when mutated, causes PXE (pseudoxanthoma elasticum), a rare genetic disease in which the skin, eyes, heart, and other soft tissue become calcified—rock hard. By 2005, scientists had genetically engineered lab mice to develop the disease. The next step would be what's called screening, in which scientists would laboriously test one molecule after another to see which had any effect on ABCC6. But "academic scientists aren't capable of creating assays [test systems] to do that," says Sharon Terry, CEO of the Genetic Alliance, which supports research on rare genetic diseases (her children have PXE). "It's time-consuming drudgery and takes an expertise that hasn't trickled down to the typical academic scientist." Ten years later, there is still no cure for PXE.
Should a lab be so fortunate as to discover a molecule that cures a disease in a lab rat, the next step is to test its toxicity and efficacy in more lab animals. Without that, no company—for companies, not academic scientists, actually develop drugs—will consider buying the rights to it. "A company wants to know, how specific and toxic is the molecule?" says Kenneth Chahine, an expert in patent law at the University of Utah. "It might work great in a mouse, but will it make a rat keel over? Doing this less fun research is not something an academic lab is interested in. The incentive driving academic labs is grants for creative, innovative research, and you're not going to get one to learn how much of a compound kills a rat."
How this culture works against finding treatments can be seen in Huntington's disease, a single-gene, fatal illness. "We have something like 300 targets [genes, pathways, and other mechanisms thought to cause the disease] and almost as many theories," says an official at a disease foundation, who asked not to be identified so as not to anger scientists he has to work with. "The way science careers are structured, big labs get established based on a theory or a target or a mechanism, and the last thing they want to do is disprove it and give up what they're working on. That's why we have so many targets. We'd like people to work on moving them from a 'maybe' to a 'no,' but it's bad for careers to rule things out: that kind of study tends not to get published, so doing that doesn't advance people's careers."
For scientists who are willing to push past these obstacles, the next one is the patent system. When Robert Sackstein was a bone-marrow-transplant surgeon in the 1980s, he noticed that fewer than 5 percent of the transplanted blood stem cells reached their target in a patient's marrow. He therefore decided to study how cells navigate, what beacons they follow. A decade-long search led to the discovery of a molecule on the surface of blood stem cells that turns out to be the master molecule used by those cells to home in on any site in the body.
Sackstein named the molecule HCELL. If stem cells were tagged with HCELL, he thought, they would make a beeline for the correct tissue—say, to regenerate bones in patients with osteoporosis. In 2008 he and colleagues announced in a paper in Nature Medicine that they had managed to do just that: when he injected human bone-forming stem cells tagged with HCELL into mice, the cells headed for the mice's bones and began forming human bone there. HCELL-tagged stem cells, in other words, could be the long-sought cure for osteoporosis, as well as other diseases that might be treatable with stem cells.
But because Sackstein had described HCELL in a scientific paper, the U.S. patent office told him it was rejecting his application. Ten years of appeals have cost hundreds of thousands of dollars in attorney fees. Sackstein fervently believes his discovery deserves a patent, and it was granted one in Europe and Japan. "You have to persevere," he says. "I can't let it go, because I think the impact on patients could be so great. We've cured osteoporosis in mice." But without patent protection, no company will develop HCELL for people, even in Europe or Japan. For a multinational drug company to go forward, it needs patent protection in the U.S. as well.
If a discovery is patented, the next step is for the university or NIH technology licensing office to find a commercial partner to develop its professors' discoveries. (The institution where a scientist works, not the scientist herself, owns the intellectual-property rights to discoveries, and thus the exclusive right to license it.) Licensing typically involves upfront fees, plus a promised share of royalties should the molecule become a commercial drug. One biotech startup in the Midwest has been trying for three years to license a discovery made when some of its founders worked at the NIH. Vascular surgeon Jeffrey Isenberg, now at the University of Pittsburgh Medical Center, and colleagues were studying how the gas nitric oxide promotes blood flow. They discovered a pathway that inhibits nitric oxide and thus impedes blood flow. By blocking the blocker—to football fans, adding an extra guard to your offensive line—the scientists got nitric oxide to open blood vessels again and increase blood flow, at least in lab animals. The molecule that works this magic is a protein called thrombospondin-1, or TSP1, suggesting that this particular offensive guard might be a potent drug for saving heart-attack victims; restoring blood flow in patients with severe diabetes, in which impaired blood flow leads to gangrene; and treating hypertension.
Unfortunately, attempts to negotiate the rights to develop this discovery were Kafkaesque. NIH's licensing office demanded payments that the startup—which, unlike the Pfizers of the world, has zero revenue—couldn't make. "NIH has no skin in the game, so they have no inducement to work with a company" to get a discovery from the lab to patients, says Eric Gulve, president of BioGenerator, a nonprofit in St. Louis that advises and provides seed money for biotech startups. "There isn't a sense of urgency." A top lab chief at the NIH laments that when scientists like himself push the licensing office to move a discovery toward commercialization, "it's just another piece of paper to them." Without the license, the startup struggles to stay alive. In its defense, Mark Rohrbaugh, the director of NIH's technology-transfer office, notes that it licensed 215 discoveries last year (though that is down from the 2004–2008 average of 273 a year, with a high of 313 in 2005). "I think we do incredibly well accommodating the needs of a company," says Rohrbaugh. "We have even linked milestone payments [made when a company achieves a goal such as starting a clinical trial] to a company raising money. The last thing we want to do is slow down the science."
If a discovery is licensed, the licensee then has to raise enough money to test the compound's toxicity (does it kill the lab rats? give them seizures?), to figure out how to make it in quantity and with uniform quality, to test the drug in larger lab animals such as dogs, and then to test it in people. Because large drug companies have been merging and retrenching (the industry laid off 90,000 people last year) and have become more interested in buying early-stage research than in doing it themselves, this role has been falling to biotech firms, which are smaller and poorer. It is at this step—turning a discovery into something that can be manufactured and that is safe and effective—that the valley of death has gotten dramatically more fatal over the last few years. "NIH grants don't support the kind of research needed to turn a discovery into a drug," says Gulve, so the money has to come from elsewhere. Traditionally, that has been venture capital. But "over the last four or five years VC funding for early-stage drug discovery has decreased dramatically," says Utah's Chahine. "You used to be able to go public, raising millions of dollars, based on a couple of genes in a rat. Now you can't even get a venture capitalist's business card for that."
Instead, VCs—essentially the only source of money to move preliminary discoveries forward—are demanding that startups prove themselves far more than in the past. Francis "Duke" Creighton had a eureka moment a few years ago: use magnets to amplify the effects of drugs that dissolve stroke-causing clots. He founded Pulse Therapeutics to develop the discovery, in which tiny magnetic particles would be mixed with a clot-busting drug, and a magnet would be used to get more of the drug to its target. He had enough money to do experiments for six months in vitro, "then we ran out," says Creighton. "Venture-capital firms said, 'Show me animal data and we'll talk,' but running animal experiments would cost $300,000 at the least." No money, no animal studies; no animal studies, no money. BioGenerator helped Creighton raise $100,000, but he's still short of what he needs.
Human testing is even more expensive—tens of millions of dollars—so commercial calculations stalk the decision like Banquo's ghost. Research funded by the Multiple Myeloma Re--search Foundation at a small biotech led to a promising new drug for multiple myeloma, a cancer of plasma cells in bones. But the firm was bought by a large drug company that decided against testing the drug in that cancer, calculating that the payoff would be greater if it could be shown to work against the big four (breast, lung, prostate, colon) or leukemias. "It's our feeling that if it had been tested in myeloma only, it would have moved faster," says Louise Perkins, chief scientific officer of the foundation.
If we are serious about rescuing potential new drugs from the valley of death, then academia, the NIH, and disease foundations will have to change how they operate. That is happening, albeit slowly. Private foundations such as the MMRF, the Michael J. Fox Foundation for Parkinson's Research, and the Myelin Repair Foundation (for multiple sclerosis) have veered away from the NIH model of "here's some money; go discover something." Instead, they are managing and directing scientists more closely, requiring them to share data before it is published, cooperate, and do the nonsexy development work required after a discovery is made.
For instance, the Chordoma Foundation, which supports research into that rare cancer, found that there was only one decent chordoma cell line in the whole world—in a freezer in Germany—and it hadn't been used for new research since 2001. The foundation obtained the legal rights to it and distributed it to some two dozen researchers, jump-starting studies that otherwise would never have been done. The cell line is being used to, among other things, screen existing drugs to see if they might work against chordoma.
Forcing that kind of cooperation among turf-jealous academics could break a lot of logjams. "There are thousands of researchers working on exactly the same thing," says Bruce Bloom, whose Partnership for Cures foundation supports research on new uses for existing drugs. "Under the current system they cannot and will not collaborate for fear that it will jeopardize funding, patent protection, and publication. Look at the progress open-source software has made in IT. Imagine the progress open-source research could make in biomedicine."
Perhaps the greatest sea change is that "more academics are starting to ask, 'How can I get funding to turn this discovery into something?' so universities are encouraging the creation of drug-development groups," says Jeff Ives, president of Satori Pharmaceuticals, a biotech in Cambridge, Mass., that is searching for Alzheimer's drugs. "The ivory-tower separation from the real world isn't acceptable anymore."
Stanford Medical School realized that. Although the NIH has increased support for research intended to help patients, points out Daria Mochly-Rosen of Stanford, there is still very little funding for steps such as testing a compound's toxicity in several species of lab animals, synthesizing the molecule, and scaling up that synthesis. "What we lack in academia is an understanding that these steps can be intellectually interesting, too," says Mochly-Rosen. To foster that, she founded Spark four years ago. It scrutinizes discoveries from Stanford scientists that have not been licensed to a company and, with industry input, identifies 20 per year that have promise. The inventor is taught the basics of drug development and gets funding support to carry out the "drudgery."
In perhaps the clearest sign that patience among even the staunchest supporters of biomedical research is running thin, the health-care-reform bill that became law in March includes a Cures Ac-celeration Network that Sen. Arlen Specter, a longtime supporter of biomedical research, sponsored. Located at the NIH, the network would give grants ($500 million is authorized this year) to biotech companies, academic researchers, and advocacy groups to help promising discoveries cross the valley of death. It may or may not make a difference. But something had better, and soon.
Source: NEWSWEEK
Proposed Changes Affecting Autism Spectrum Disorders in DSM-V
Asperger's, PDD-NOS may no longer receive separate diagnoses
Recently, the American Psychiatric Association released some preliminary draft changes to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) that may affect those diagnosed on the autism spectrum. There are several significant changes proposed that are now posted for public view, including: Asperger’s Syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) would both be subsumed into the Autistic Disorder category, meaning that they would no longer be considered a separate diagnosis from autism, and the inclusion of potential co-morbidities with ADHD and other medical conditions.The Autism Society is currently investigating the implications this change could have for the service and support systems currently in place for those with autism spectrum disorders. We will also be holding a town hall meeting at the Autism Society’s National Conference on Autism Spectrum Disorders in Dallas July 7-10, 2010 (learn more about the conference or register at www.autism-society.org/conference). You can also give your feedback on the changes at the Web site www.DSM5.org – look for the diagnoses on the autism spectrum under “Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence.”
These changes are not yet official – they are proposed for the update to the manual, which is expected to be published in May 2013. Whatever changes do go into effect surrounding autism spectrum disorders, the Autism Society will continue to work as we have always done to improve the lives of people across the entire spectrum of autism.
Source: Autism Society
Sunday, May 16, 2010
Gloucestershire mother, 81, wins UK carer award
Heidi Ravenscroft suffers from the neuroglogical condition Rett syndrome
An 81-year-old woman from Gloucestershire has been named carer of the year for looking after her daughter who has a rare brain disorder.
Anne Ravenscroft from Whitecroft has four children and has taken care of 46-year-old Heidi, who is unable to talk and is a quadriplegic, since birth.
She was nominated for the award by her husband and said looking after Heidi was "normal life and a joy".
Reg Ravenscroft, 82, said his wife was wonderful and had kept Heidi alive.
Luxury holiday
Mrs Ravenscroft said: "If you have a child, you naturally nurture it, rear it and bring it up until such a time as they can go off on their own.
"Well Heidi never reached that stage, so it was a continuation of bringing up a child.
 Heidi seemed to be a healthy baby when she was born in 1964 |
Heidi seemed to be a healthy baby when she was born in 1964 but started to regress at the age of 18 months.
Over a period of years she lost the ability to walk, speak and to feed herself.
She was finally diagnosed with the neurological condition Rett syndrome at the age of 23.
Mrs Ravenscroft won the UK parent carer and overall carer of the year award which is organised by Bupa. Her prize is a luxury holiday worth £5,000.
Source: BBC News
Saturday, May 15, 2010
International Rett syndrome Foundation: Pillar of Hope and support for Rett Families all around the world
Source: International Rett syndrome Foundation
Thursday, May 13, 2010
CDC Commentary: Screening for Autism and Developmental Delays -- Learn the Signs
Georgina Peacock, MD, MPH
SOURCE: MEDSCAPE
SOURCE: MEDSCAPE
Best Evidence Interview: Older Parents and Autism -- Questions on the Rise in Autism Continue
Expert Interview With Judith K. Grether, PhD
The Best Evidence Study
Risk of Autism and Increasing Maternal and Paternal Age in a Large North American Population
Grether JK, Anderson MC, Croen LA, Smith D, Windham GC
Am J Epidemiol. 2009;170:1118-1126
Am J Epidemiol. 2009;170:1118-1126
This study was selected as the subject of this interview because of its high ranking in Medscape Best Evidence, which uses the McMaster Online Rating of Evidence System. Of a possible top score of 7, clinicians who used this system ranked this study as 5 for relevance and 7 for newsworthiness.
About the Interviewee
Judith Grether, PhD, is Senior Epidemiologist in the Environmental Health Investigations Branch, California Department of Health Services. Dr. Grether is a perinatal epidemiologist who has had the opportunity over many years, within the California Department of Public Health, to conduct research studies on the prevalence of and risk factors for developmental disabilities, primarily cerebral palsy and autism spectrum disorders. She has recently retired and is now working to complete some analyses and manuscripts.
Medscape: Your study, "Risk of Autism and Increasing Maternal and Paternal Age in a Large North American Population," was highly ranked by pediatric clinicians. Could you just give a brief description of it and its significance?
Judith Grether, PhD: Our study was the largest that has yet been conducted -- and, I would guess, is probably the largest that will be conducted -- to specifically address the question of whether the risk for autism in offspring increases with the advancing age of the mother and/or the father. With our very large study, we were also able to obtain statistically precise estimates of how much of an increase in risk there is as parents get older. A number of prior studies have looked at the question of a parental age effect; to my knowledge, none have reported adecreasing risk as parents get older, but some have found an increased risk only for advancing maternal age and others only for advancing paternal age. A couple of studies have pretty dramatic estimates of the amount of that increased risk -- particularly one from Israel that found only father's age to be important. From a scientific perspective, to get clues to what may underlie any increase in risk for autism associated with older parents, it is important to answer the question: is it both age of the father and the mother, or is it only mothers or only fathers? There are some tricky statistical issues here and it is very helpful to have a large database like we had, in which the subjects are not self-selected for the study.
Medscape: Where did you get your data from?
Dr. Grether: We analyzed data from the California Department of Developmental Services (DDS), which is a statewide service system in California for people with developmental disabilities. It is a well-established, well-known program that has been around since, I believe, the late 1970s. Children and adults with autism, mental retardation, cerebral palsy, epilepsy, and related conditions are eligible to receive services if they meet diagnostic and severity criteria. It is an entitlement program, so there are no income or citizenship criteria. The program has a database that, I believe, has used the same data collection instrument since 1987 to document eligibility for services.
With the appropriate approvals from DDS and our institutional review board (IRB), we were able to obtain a data file that contained eligibility diagnoses for children born in 1989-2002. We then linked the DDS data to the statewide birth certificate files, again with IRB approval and strict requirements to maintain the confidentiality of the data, to obtain demographic data, such as parental age, [that had been] recorded before there was any concern that a child might have a developmental disability. The DDS data are assembled for administrative purposes, so the database has definite limits for research studies, especially with regard to diagnostic details and potential underlying causal factors. However, DDS data are extremely valuable for looking at broad-stroke time trends and demographic patterns. And so, it is really very useful for some types of studies.
After we had excluded multiple births and subjects with missing data, we were able to analyze the demographic characteristics of more than 20,000 singleton children born to California residents who were receiving DDS services for autism and compare them to the remaining 7.5 million singleton children born to California residents during those same 14 years.
Medscape: Did these children in your dataset have classic autism or were they part of the autism spectrum?
Dr. Grether: Well, that is part of the complexity here. According to DDS eligibility guidelines, a child is supposed to have autistic disorder or have mental retardation with sufficient severity to meet the criteria to be getting services. In reality, partly because the diagnosis of autism is based on behavioral criteria, the distinction between autistic disorder and other spectrum conditions can be rather "soft." We know through experience that there are some children receiving DDS services for autism who may not, in some clinicians' eyes, meet the full DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] criteria for autistic disorder. However, these are clearly not typically functioning children; they need services and there may be nowhere else to send them. So, sometimes the eligibility criteria likely get interpreted a bit leniently. None of this, I think, is particularly relevant to our concerns in this study. It has restricted some other analyses, but is not so relevant here.
Some unknown proportion of children enrolled with DDS are probably somewhere else on the spectrum, and there also children receiving services from DDS who have autism but whose eligibility diagnosis is mental retardation. We have no way of teasing this apart unless we actually go into the hard copy records, which we have done for some other studies, but not for this one, given the very large size of this study. The bottom line is that we can't make any claims about autistic disorder vs other spectrum disorders, so we have to be careful here, especially when looking at time trends.
Medscape: Would the fact that children are entering the system who actually don't meet the strict autism criteria be responsible for the increase observed over the past decades?
Dr. Grether: Clearly, there has been a huge increase in children with autism coming into the DDS system, and as epidemiologists, we have spent a lot of time trying to figure how much of that increase is likely attributable to children with other spectrum disorders coming into the system, and how much is likely due to other factors, such as more awareness or that there are now treatments for eligible children. We know all of those things go on, and also that diagnostic criteria have changed over time. The basic question is, from an etiologic standpoint, how much of the increase may be real, in the sense that something new is going on that was not there before and that contributes to some children having autism.
Medscape: So, you can't tell what percentage of the increase might be due to this broader diagnosis.
Dr. Grether: No, to really get a good handle on that, you would have to do a study in which you go into a community, you try to find every child who may be anywhere on the spectrum, and you give all of them the gold standard diagnostic evaluation. That is a very expensive and time-consuming kind of study.
Medscape: I suppose if you saw autism leveling off now, it would be some indication that a fairly significant percentage might be due to broader diagnostic or socioeconomic factors.
Dr. Grether: If the eligibility criteria for programs like the DDS included anybody anywhere on the spectrum, then you would expect there would be an influx of new kids coming in who meet the broader diagnostic criteria. The numbers would go up accordingly and then level off after that if nothing else was changing to lead to bigger numbers. Obviously, we cannot go backward in time and reconstruct such a scenario, so we have to live with uncertainty.
Medscape: Are there any other factors that you could hypothesize might be going into the increase in autism?
Dr. Grether: Many environmental factors have been raised as possibilities, because obviously, many things have changed in our environment. The difficulty is that most of the things that we worry about -- water and air contamination, plastic hardeners in the sports water bottles, etc. -- are very hard to study in a rigorous way. It is a huge methodological challenge and, fortunately for all of us, some talented scientists are trying to do these studies. Some years ago, after trying to tease out how-much-is-real-and-how-much-isn't kind of question, some of us got to the point of saying, you know, folks, we are never going to have the occurrence data to really figure this out in a satisfying way. Let's stop devoting some much of our precious time and energy to this question, and let's try to figure out what is going on in our environment that could be relevant here. Even if all these new environmental exposures and other changes in our environment are not contributing to autism, per se, we need to know more about them because autism is only one of many pediatric disorders that could be linked to environmental factors. Let's do our best to design studies to really try to narrow in on some of it. It is a huge challenge.
Medscape: What about genetic factors?
Dr. Grether: Genetic studies are going on, and talented researchers are finding more and more genetic factors that may contribute. But from everything we know about the human condition, environmental factors are likely to also play a role.
Medscape: To get back to your study, older parenting has been increasing, so might this also contribute to the increase in autism?
Dr. Grether: Yes, the typical age of parents has been going up somewhat. We have done an estimate, not yet published, in which we basically took the demographic profile of the statewide population in 1989 and applied it to the statewide population in 2002. This standardized the 2002 population for the demographic profile in 1989, permitting us to estimate how much of the increase in DDS-reported autism was either reduced or exacerbated by changing demographic patterns. It was somewhat reduced, but not by a lot. Overall, the changing demographics of the population, including increasing age at parenthood, seems to explain some small part of the increase we see. In a recent paper, colleagues at UC [University of California]-Davis used DDS data and came up with an estimate that 4.6% of the increase in DDS-reported autism from 1990-1999 may be attributable to changing parental age patterns. That's a very modest portion. Clearly, the fact that parents are typically somewhat older than they used to be is not the main explanation behind the increase in autism that we are seeing.[1]
Medscape: What was the significance of your results on older parenting and autism?
Dr. Grether: Our results were certainly consistent with what other people are reporting using California data and also with other studies conducted elsewhere in the world. Both mother's and father's age matter, there is both a maternal and a paternal age effect, and in our study, the maternal age effect is somewhat stronger. However, the increase in risk for autism in offspring born to older parents is pretty modest and probably not useful as a guide in personal decision-making. The real benefit of our study and similar ones is that we now have a scientific clue that may help point us toward underlying biological factors that contribute to the risk for autism in some children. We needed to pin down whether advancing parental age really matters or if it is just some kind of statistical artifact. We can now have confidence that there is a modest parental age effect for both mothers and fathers (at least in the US population). Our task now is to try to figure out why the risk of having a child with autism is greater for older parents.
Medscape: Can you give us some background on why parental age may affect the risk for autism?
Dr. Grether: There are 2 sets of factors, they are not mutually exclusive, and both may well be important. One set of factors involves biological changes that occur as men and women get older and that can affect the outcome of the pregnancy. Down syndrome would be an example of an outcome we know is sometimes related to maternal age. For women, as they get older, the hormonal balance of the womb changes in some ways, and older women are more likely to have infertility. There has been speculation that the hormonal changes that contribute to infertility, or the treatments for infertility, may increase the risk for autism, but we don't have very good data yet. As a woman ages, she will have an increased cumulative exposure to chemicals and toxins in her environment that may affect the neurodevelopment of the fetus. Again, there are not very much data there, but it makes good biological sense to conduct research on environmental factors to which the mother is exposed before or during pregnancy that may affect fetal neurodevelopment.
Medscape: How is male reproduction affected by aging that might influence the risk for autism?
Dr. Grether: Unlike eggs, which were formed during fetal development of the mother, the process of sperm creation and maturation is ongoing, and it is now recognized that as men get older, typically there are more new mutations that occur in the sperm, that are developing. Again, it could be related in some ways to cumulative toxic exposures as men get older. Several studies have demonstrated that, in families lacking a history of schizophrenia, there is an association between older age of fathers (but not mothers) and risk of having a child with schizophrenia, presumably due to more de novo mutations in sperm. These studies of young-adult schizophrenia provide a model that may be relevant to autism, but the studies needed to clarify this for autism have not yet been reported.
The data we and others report showing both a maternal and a paternal age effect for autism could indicate that genetic mutations to the sperm contribute to the risk for autism in the children, but clearly that is not the whole picture because we also see a maternal age effect. That is one reason why we are so interested in studying hormonal factors in the mother during or before pregnancy that may contribute to autism risk.
Medscape: Are there reasons, other than biology, why this risk exists in older parents?
Dr. Grether: There is another possibility here, another possible explanation that could also explain the parental age effect. Over and above whatever reproductive biological changes happen as people age, people who are predisposed to have an autistic child may be more likely to start having children later in life, for a variety of reasons. They may be going to college, pursuing more intensive careers, and putting off childbearing until later. We can speculate about these reasons, but we don't yet have studies on this and, unfortunately, we don't have relevant data from our study.
There is also speculation in the research literature that, to the extent there is a tendency for people to have children with a partner who is similar to themselves ("like marries like"), there may be a pattern for people with a genetic predisposition for autism to form a relationship with a partner who has a similar genetic predisposition. By waiting until later in life to have a family, perhaps there is more opportunity to find a partner with similar underlying genetics, thereby increasing the genetic risk in the child.
As I said, this is speculation at this point. The studies simply have not yet been done. The "takeaway" message here is that we now have some good hypotheses around which to conduct further studies that will help in disentangling the mix of genetic and environmental factors that contribute to autism.
Medscape: Did you find any greater association with autism and any ethnicity or race in older parents?
Dr. Grether: No, not with the increasing parental age. It was really very, very similar across racial ethnic groups, which is really interesting.
Medscape: What about socioeconomic groups?
Dr. Grether: We found an association with one SES [socioeconomic status] measure (private insurance payment for the delivery vs other sources of payment, primarily government programs for low income people) but not with another (educational level attained by the mother or father), so our findings must be considered to be inconclusive with regard to socioeconomic status.
Medscape: Haven't there been some studies indicating that higher economic groups are more prone to autism than lower?
Dr. Grether: Yes, but that is really a different question. Let me try to restate it, as this can be a real mind-twister. In our parental age study, we were trying to look at how much an increase in the age of parents is related to the risk for autism in a child. We were not looking at the baseline risk. So when I say that we did not see a difference in the increase in risk associated with age of parents for well-educated parents compared with less well-educated parents, what I am talking about is the increase associated with the parents being older. At any given age, well-educated parents are more likely to have children with autism than less well-educated parents (and we don't know why this is so), but the amount that the risk increases with increasing age of parents is the same for both groups. Their baseline risk may be different, but the rate of increase in risk represented by the upward slopes of the lines are parallel to each other.
Medscape: Are there any other factors that might affect the risk of having a child with autism among older vs younger parents?
Dr. Grether: One finding that we have, which most other studies have not examined, is that both the maternal and paternal age effect is stronger among first-born children than among later-born children. For first-born children, both for mothers and fathers, that slope with increasing parental age is steeper than for later-born children. So, if it is the first time a parent is having a child, the risk of that child having autism is greater than for a child of a parent of comparable age who already has children.
The explanation for this pattern may be that parents starting their families later in life have a pre-existing risk and so we would see this pattern more strongly among first-born children. It certainly should not matter if it is the first-born child for that older father or the fifth-born, since the sperm at that older age would still be going through the same genetic changes.
Medscape: Does the higher risk in first-born children hold up with women as well as men?
Dr. Grether: Yes, the maternal age effect is stronger in first-born than in later-born children. For a woman has had prior children, prior pregnancies may change the in utero environment in ways that affect her fetus differently than is typical for a women of the same age having her first child. Or perhaps the effect of toxic exposures from the environment is different, depending on the reproductive history of a woman giving birth for the first time compared with one who has given birth before.
My guess is that when we have the answers to all the questions raised by our study and others that have addressed the question of a parental age effect, we will see that both delayed childbearing and age-related biological changes contribute to the higher risk for older parents. But until the research is conducted, we won't know. A recent letter to the editor in the American Journal of Public Health by some colleagues basically said, and I fully agree, that studies, including ours, have consistently established a parental age effect. Now it is time to move on and figure out why.[2]
Medscape: Do you see prenatal screening anytime in the future?
Dr. Grether: No. I don't think we are close to having prenatal screening. In the meantime, as a society, we need to work through the deep ethical issues involved. Our current best understanding is that autism spectrum disorders are at one end of a human continuum, raising complex questions about the kind of society we want to fashion as science changes and the possibilities for medical interventions increase.
Medscape: Just as an aside, our news group covered the Lancet article that retracted the study associating autism with vaccinations. Do you have any thoughts on this and the problem of convincing fearful parents to immunize their children?
Dr. Grether: It has always surprised me how many people confuse the various concerns that have been raised regarding childhood immunizations and risk for autism. The Lancet retraction focused on the MMR [measles, mumps, and rubella] vaccination and the allegations by a team of researchers in Great Britain about MMR playing a role in autism in some children. The MMR-autism connection has now been demonstrated to have been based on very shoddy, perhaps even falsified, evidence. There is no scientific basis that I am aware of for being concerned about MMR and autism. Another issue about vaccines is the thimerosal preservative that was included in multidose vials of some other childhood vaccines (thimerosal was not in the MMR vaccine). Here there have been many studies and no credible study has found a link between thimerosal exposure through vaccines and autism. In the United States, thimerosal exposure from vaccines is no longer an issue, except perhaps through some flu shots. The other concern that I have heard voiced is that the recommended childhood vaccine schedule now includes so many vaccines and that children are thereby being exposed to more antigens than previously. Although there are now more vaccines recommended for children, the total antigen exposure from today's vaccines is considerably less than in earlier years because of advances in vaccine composition. And compared to the sheer volume and diversity of antigens in a typical environment, the antigen dose received in vaccines is minor. While it is understandable that parents, and perhaps some clinicians, have raised the alarm about vaccines, I am not aware of any credible evidence to support these concerns.
Medscape: To conclude, and I think you really answered this already, do your results have any implications for personal decision-making or clinical practice?
Dr. Grether: You know, I wish they did, but I really don't think that they do at this point. The increase in risk that comes with older parents is really quite modest and we don't know what is behind it. I think the main benefit of our study and other similar ones is to alert us to an important etiologic clue, and it is now time to find out what is going on.
References
- Shelton JF, Tancredi DJ, Hertz-Picciotto I. Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Res. 2010;3:30-39.
- Reichenberg A, Gross R, Sandin S, Susser ES. Advancing paternal and maternal age are both important for autism risk [letter]. Am J Public Health. 2010;100:772-773
SOURCE: MEDSCAPE
CDC Commentary: The Three Faces of Autism Spectrum Disorder -- Learn to Recognize Them
Marshalyn Yeargin-Allsopp, MD
Autism spectrum disorders or ASDs are a group of developmental disabilities that can cause significant social, communication, and behavioral challenges. People with ASDs share some similar symptoms, such as problems with social interaction. But there are differences in when the symptoms start, how severe they are, and the exact nature of the symptoms.
There are 3 different types of ASDs:
Autistic disorder also called "classic" autism. People with autistic disorder usually have significant language delays, social and communication challenges, and unusual behaviors and interests. Many people with autistic disorder also have intellectual disability.
The second type is Asperger syndrome. People with Asperger syndrome usually have some milder symptoms of autistic disorder. They might have social challenges and unusual behaviors and interests. However, they typically do not have delayed language or intellectual disability.
The third type is pervasive developmental disorder - not otherwise specified or PDD-NOS, also called "atypical autism". People who meet some of the criteria for autistic disorder or Asperger syndrome, but not all, may be diagnosed with PDD-NOS. People with PDD-NOS usually have fewer and milder symptoms than those with autistic disorder.
CDC's most recent data show that between 1 in 80 and 1 in 240 children with an average of 1 in 110 have an ASD. This is a prevalence of about 1%. It should also be noted that ASD prevalence was 4 to 5 times higher for boys than for girls. This study also showed there were concerns regarding development before the age of 24 months in the evaluation records of most children, but the average age of earliest ASD diagnosis was much later, at 54 months.
There are different methods to evaluate and diagnose autism. These include developmental screening and a comprehensive evaluation. Developmental screening is a short test to tell if children are learning basic skills when they should, or if they might have delays. During developmental screening the doctor might ask the parent to fill out a questionnaire on how their child learns, speaks, behaves, and moves. A delay in any of these areas could be a sign of a problem.
A comprehensive evaluation is a thorough review that may include looking at the child's behavior and development and interviewing the parents. It may also include a hearing and vision screening, genetic testing, neurological testing, and other medical testing. In some cases, the primary care doctor might choose to refer the child and family to a specialist for further assessment and diagnosis.
Specialists who can do this type of evaluation include:
- Developmental pediatricians;
- Child neurologists; and
- Child psychologists or psychiatrists.
There are many tools to assess ASDs in young children, but no single tool should be used as the basis for diagnosis. Diagnostic tools usually rely on 2 main sources of information -- parents' or caregivers' descriptions of their child's development and a professional's observation of the child's behavior.
It is important to remember that studies consistently show that early identification and intervention can improve long-term outcomes for children.
For more information on autism spectrum disorders, please visit the Website listed on this page or visithttp://www.cdc.gov/autism. Thank you.
Citation
Centers for Disease Control and Prevention. Autism Spectrum Disorders (ASDs). Available at:http://www.cdc.gov/ncbddd/autism/index.html Accessed April 30, 2010.
Source: Medscape
The Current State in Autism -- Still Tough to Treat but Encouraging Progress
An Expert Interview with Fred R. Volkmar, MD
Introduction
As part of a special feature on autism, Medscape interviewed Fred R. Volkmar, MD, one of the world's leading experts on autism, to get his view on the current state in autism and autism spectrum disorder. Dr. Volkmar is the Irving B. Harris Professor of Child Psychiatry, Pediatrics, and Psychology and Director of the Yale University Child Study Center, Yale University School of Medicine. He is also the Chief of Child Psychiatry at Yale-New Haven Hospital, New Haven, Connecticut. He was the primary author of the American Psychiatric Association's DSM-IV's (Diagnostic and Statistical Manual, text revision IV) section on autism and pervasive developmental disorders section, and the author of several hundred scientific papers, chapters, and books. He also serves as the editor of the Journal of Autism and Developmental Disorders. Dr. Volkmar has been the principal investigator of several major grants for autism research.
Medscape:Let's start with big picture, the world view, of autism, ok?
Fred R. Volkmar, MD: The big picture -- which is why this is more relevant than an academic exercise -- is that there are very strong reasons to believe that, with earlier detection and intervention, children with autism are doing better and better. One of the happy problems we have these days is supporting kids with autism, Asperger's, and autism spectrum disorder who go to college. It's a problem that didn't happen so much in the past, but it's happening more and more. This has its own pros and cons because these young people have their own sets of issues, but it's a happy problem to have. It also is the case that more and more resources are becoming available for professionals as well as parents and teachers.
Medscape: Can you give us some examples?
Dr. Volkmar: Well my wife, a pediatrician, and I co-authored a book specifically written for parents and teachers.[1] Also for the past 25 years I've taught an undergraduate seminar at Yale College where the students have weekly supervised experience working with children and adolescents on the autism spectrum and a seminar on a range of topics including diagnosis, braining functioning, genetics, early development, communication problems, behavioral programs, and so forth -- lectures given by Yale faculty or occasionally invited lecturers. We have been fortunate to have support from donors, which has allowed us to make the entire series of lectures public on the Internet.
Medscape: That is a great resource. Can you frame for us why these are important issues? For example, what are the economic issues with autism?
Dr. Volkmar: They are not trivial. Some good data have been published both here in the United States and in the United Kingdom about how much it costs for someone with autism to end up living in an institutional setting, with 24/7 care. We're talking millions of dollars per person.[2,3] So, with improvement in outlook for these patients, we're seeing the difference between somebody who's a tremendous financial drain on society as opposed to someone who is a taxpayer and is out there working, maybe getting married, and productive. So this is not a trivial issue. Many people with developmental disorders are now getting better -- and notice I say many, not all, because, unfortunately, not everyone gets better, even with early diagnosis, but more and more do.
Medscape: Are you seeing more patients with autism than you did earlier in your career?
Dr. Volkmar: When I came here in 1980 to do a fellowship in child psychiatry, seeing a 4- or 5-year-old with autism was a big deal. "Oh, this is amazing." In some ways this was paradoxical though, because, from the first description, autism has been generally thought to have its onset in the first months of life -- if not from birth. Part of the reason was lack of information on the part of the parents, but also pediatricians and healthcare providers were not realizing what the problems were and often gave the standard advice of "wait and see." It is now very common to see children with autism who are under a year -- I think the youngest child that we've seen and worried about was 3 months old.
Medscape: How have researchers studied young children?
Dr. Volkmar: This is an area where research has changed. In the past it was typical to rely only on parent report. The trouble is that when you're dealing with parents they may not be very good at remembering and many different factors can color their recollection. This gets to be even more of a problem as the child gets older. I have the same problem. You ask me, "Which one of my kids talked first and what month? What was their first word?" Well my wife might remember. I'm not sure I could, and the older that kids get, you have what are called telescoping effects. There are complicated issues in relying on people's memories, particularly for things that might seem, at the time, relatively subtle.
So, what are other ways we can go? The next thing researchers tried was to look at videotapes. There was a whole body of work looking at videos, let's say, first birthday videos, and finding some subtle deficits in many children and often by the second birthday lots of deficits. Indeed many of the items that current checklists and screeners include rely on focus on signs of autism from around age 18 months to 2 years. However, the videotape work had its own issues. Often you're looking at one particular context -- birthdays, Christmas, Hanukkah. It's not like a standardized setup or package of observations, but nevertheless, this gives us some information and helps us document some of the early features.
Leo Kanner, when he described autism, said children were born with it.[4] He thought it was congenital, and most of the time we think that's probably true. What's happened in the past 10 years is that people have really clued into how strongly genetic autism is, which also means that they're thinking about risk for siblings -- who have a risk probably somewhere between 2% and 10%. This has given rise to some new and very interesting strategies. Over the past few years, there have been a number of studies, mostly prospective, in this country, and some in Canada and other countries. These studies are following siblings of children already diagnosed with autism from birth and observing autism as it first develops. We have recently edited an entire book devoted to the topic of autism in infants.[5]
Medscape: What research is going on at Yale in this area?
Dr. Volkmar: Here at Yale, we have a large interdisciplinary group looking at early development by using eye contact and listening preference. We have a series of studies using neuroimaging methods such as magnetic resonance imaging and functional magnetic resonance imaging to study brain functioning, and another series of studies concerned with genetic mechanisms. Still others are look at issues of treatment and the evidence base of treatments. Our Web site has descriptions of these studies as well as links to good resources.
Medscape: What are some of the ways clinicians can learn more about early diagnosis? Are blood tests available that will help to diagnose autism?
Dr. Volkmar: There are very promising leads in the area of genetics, with some potential candidate genes now being identified. We also know that autism is sometimes associated with other conditions, such as Fragile X and tuberous sclerosis. On the other hand we don't have simple genetic tests as yet and so clinician awareness and screening remains the major thing we rely on in picking up cases early in life. The Centers for Disease Control (CDC) and American Academy of Pediatricians have good resources on autism for clinicians. And the Yale seriesI mentioned previously has lectures on diagnosis, genetics, and early development in autism.
One of the very active areas of research is development of better ways to detect autism early in life.
Medscape: How long would it take to be able to introduce diagnostic criteria into practice based on prospective studies?
Dr. Volkmar: If you're doing a study that started, say, 4 or 5 years ago, only now would could you be absolutely sure of the diagnosis of autism in those kids. There's intrinsically a bit of a time delay built in there.
Medscape: By the way, when you say autism, are you talking about classic autism or the autism spectrum disorder?
Dr. Volkmar: That's another very interesting question. It depends on how you want to phrase it. When I say autism, I usually mean classical autism. Autism spectrum is very au courant, and it's probably 4 or 5 times more common than classical autism and not unrelated to it in terms of genetics and, indeed, interventions. On the other hand, most of the research is done on classical autism. There's been very little on the broader spectrum, comparatively speaking. There's even less agreement on the best ways to come to a good definition of the broader spectrum. The autism spectrum is a very interesting conundrum because that's when you here, "Oh, the chance of your kid going to Carnegie Hall is like the chance of your kid having autism." they're not talking autism, they are talking autism spectrum disorder (ASD).
Medscape: Do you think the increase in autism is mainly due to the expanded definition?
Dr. Volkmar: It's a couple of things. First of all, there's more public awareness. The fact that we're having a discussion like this, 20 years ago nobody would have ever called me to talk about autism. It's partly the media and it's organizations like Autism Speaks and other things for good or bad. Even on the Internet, if you type in autism into Google, you will get 15,000,000 hits. The trouble is, only about 100 of those are worth anything and of that 100, about one third are quite problematic. There's more information, there's more media attention, there's more public awareness. We now get referrals from daycare providers, who in the past wouldn't even know what the word meant. It's much more in the public conscientiousness.
Back in 1994 when we revised the most recent DSM, we made a conscious effort to be sure the system worked well for more cognitively able people. That was going to increase the numbers, not because people with ASD weren't there before, but they weren't said to have autism because they were brighter.
Medscape: What are the public implications of the expanded definition of autism?
Dr. Volkmar: I was just having this debate with a faculty member. It's fascinating because I can tell you that when you say we're going to move from autism to autism spectrum, the public schools are not going to magically increase their budget 5 times for special ed. They're going to be dealing with the same pool of money, only it's going to be spread out more. So one of the questions is going to be: "What does this do for the kids with classical autism?"
It's a very interesting time to be involved in autism research, and there's a lot to be said about the earlier diagnosis business. However, I think one problem in the field is that although there's some very interesting research done over the past decade that is just starting to permeate out, people have not done such a great job thinking about the implications -- what does it mean in terms of clinical interventions, clinical services. I think people are trying for the first time to really translate some of the research knowledge into information that parents and teachers and clinicians can use.
Medscape: So is early intervention in autism and ASD making a difference?
Dr. Volkmar: There's a wonderful book if you haven't seen it called, Educating Children With Autism, it's from the National Research Council.[6] It came out in 2001 and it answers a question that was asked by the US Department of Education, "Does early intervention make a difference in autism?" The answer was yes. This book goes through 10 programs around the country that have published peer-reviewed information showing their program works, but they're mostly focused on autism. It's a funny business, because I would say to parents, "Your child isn't so much classically autistic; they're only on the spectrum." The parent would say, "Well I can't find much about that." I would say, "Yes, it's a paradox because this is the more common condition." Researchers who want to get grant funding have had to basically focus on autism because there's been much less agreement about defining the broader spectrum. It's a very difficult conundrum.
There are, however, some good materials for parents now -- good books, and I think there are some good Websites. I edit the Journal of Autism, which is the oldest one in the field, and we have 2 papers under review right now that are looking at Internet resources and the quality of information, which is a great topic.
Medscape: Are there any medical interventions that might be useful?
Dr. Volkmar: There are some good pharmacologic interventions. They can help with some of the behaviors -- the irritability, the agitation, the stereotype movements and mannerisms, which can be very problematic in terms of programming. So, these are important interventions, However, they don't seem to target the core social communication problem.
Medscape: You had done a study on citalopram.
Dr. Volkmar: It was one of my colleagues here who was involved in citalopram. I wrote a commentary for the archives. It basically made the point that it doesn't work so well for kids. It seems to work better for adults, and again, that's one of the problems. The drug companies have not been very interested in autism as a topic area. There's been some interest, but not much.
Medscape: Does oxytocin have any promise?
Dr. Volkmar: This is complicated one. The thing about oxytocin, you could make a case for it around attachment, but the interesting thing is that when people have looked at children with autism, they do develop attachments to their parents. They also develop odd attachments to other things. So it's not like they don't develop attachments. It's an interesting discussion, and oxytocin's one the agents, obviously, that people are interested in because it involves a direct social connection, but we need more work in the area.
Medscape: How early can you start working with these children?
Dr. Volkmar: In this country, we mandate services in school starting at age 3. Some states have early intervention programs before that time, but they differ dramatically. And the states vary in terms of the range and quality of programs provided in schools. In Connecticut, for instance the kinds of service will vary a lot depending on the town you're in.
The report from the National Research Council[6] makes the suggestion -- and it's a somewhat odd number -- of 25 hours a week, year round, for a program. It's a funny number because the actual programs range from 40 hours a week to less than 10, and the programs themselves vary so the 25 is a kind of middle-of-the-road number. For instance some programs are center-based, where a parent comes in, gets trained, and then goes home. Other services are provided in the home. There are all kinds of interesting different models and to complicate life further, all these programs change and evolve over time. They may start out more center-based and then move into schools. It's very interesting, but we, as a country, try to make more sense out of what programs work for what kids. I'm sure there are some programs that don't do as well as others. So what can we learn from mini-experiments that are going on around the country, in terms of, what does and doesn't work or what can we do to make programs more effective?
Medscape: Is there anything specific that you could describe as an intervention that would be effective?
Dr. Volkmar: Special education and behavior modification.
Medscape: What about interaction with a parent?
Dr. Volkmar: That's not a bad thing and obviously it can be very helpful. I would emphasize some programs more than others. Some of the more developmentally based programs want to get parents on board, which turns out to be complicated for many reasons. There are less data for those programs than there are for the behavioral programs. It's also a horrible burden for parents if they're charged with delivering a program and then it doesn't work. Who's responsible for that? There's a big potential for parents feeling dreadful if they're the ones bearing the burden of the program. The happy news is that there are really good programs around the country that can serve as models.
Medscape: So how would you summarize the best approach for intervention?
Dr. Volkmar: The most relevant book, which I mentioned from the National Academy, Educating Children with Autism, makes the point that there are several intervention programs that have some data that show that they work and that they can work quite well. Many of them are based on aspects of behavior modification called "applied behavior analysis" interventions; many of these have become very sophisticated. Others are more developmentally based and/or eclectic and pull bits and pieces from other things, but the goal, basically is that autism becomes a problem for learning. If you're not socially engaged and you're sitting in that first-grade class, the world is equally relevant to either the world of the teacher, the world of the wallpaper, the world of the fan spinning in the ceiling, or the world of carpet in the floor, and so it's a real problem for kids. It's a challenge for learning. A lot of the focus of these early intervention programs has to do with mitigating the problem behaviors of autism that interfere with learning. As a result, it looks like kids are doing, as a group, much better in terms of their learning effectively. This sets the stage for their being able to be more able to participate actively in learning and for future success.
References
- Volkmar RR, Wiesner LA. A Practical Guide to Autism: What Every Parent, Family Member, and Teacher Needs to Know. Hobokon, NJ: John Wiley & Sons; 2009.
- Knapp M, Romeo RE, Beecham J. Economic cost of autism in the UK. Autism. 2009;13:317-336. Abstract
- Ganz ML. The costs of autism. In: Moldin SO, Rubenstein JLR, eds. Understanding Autism: From Basic Neuroscience to Treatment. Boca Raton, Fla: Taylor and Francis Group; 2006.
- Kanner L. Autistic disturbances of affective contact. Nervous Child. 1943;2:217-250.
- Chawarska K, Klin A, Volkmar FR, eds. Autism Spectrum Disorders in Infants and Toddlers: Diagnosis, Assessment, and Treatment. New York, Guilford Press; 2008.
- National Research. Educating Young Children with Autism. Washington, DC: National Academy Press; 2001.
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