May 13, 2011 —
Efforts to increase awareness about the early signs of autism appear to be working, a new study shows.
Researchers with the CDC, Harvard Medical School, and United Health Group found that the number of children younger than age 3 who were enrolled in early intervention programs for autism spectrum disorders (ASD) in Massachusetts rose 66% in children born between 2001 and 2005.
Mounting evidence suggests that the impairments of autism -- including deficits in speech, IQ, and social skills -- can be tempered or even reversed if therapy is started early.
So the government has funded public health campaigns to increase awareness of the first signs of autism and the importance of early diagnosis among parents and health care providers.
Some states, including Massachusetts, have passed laws mandating insurance coverage for early interventions.
Advocacy and professional groups have also ramped up their efforts to encourage early diagnosis, and there's been more media coverage of the disorder, says study researcher Susan E. Manning, MD, MPH, an epidemiologist with the CDC and the Massachusetts Department of Public Health.
Taken together, she says, those efforts are probably responsible for much of the increase observed in the study.
Experts who were not involved in the study say that to the extent the increase in early diagnosis is a reflection of successful public awareness efforts, it is positive news.
"This is exactly what researchers who are working so hard to identify the early markers of autism and to develop these efficacious early interventions want to see happen," says Rebecca Landa, PhD, director of the Center for Autism and Related Disorders at Kennedy Krieger Institute, Baltimore.
But researchers could not rule out the possibility that some of the new diagnoses represented an actual uptick in affected children.
"Some of this could be due to an actual true increase in autism," Manning says, "But how much of that, of the overall increase, is accounted for by a true increase in autism is hard to tease out because all the other factors come into play."
Expansion of Autism Symptom List
Other experts say the increase noted in the study probably also reflects the expansion of symptoms that are used to define autism spectrum disorders. They worry some young children may be getting a diagnosis based on symptoms they'll eventually outgrow.
"Because ASD now includes only a few symptoms of classic autism, children who previously were not diagnosed with ASD are now being identified," says Stephen Camarata, PhD, an autism specialist and professor of hearing and speech sciences at Vanderbilt University in Nashville, Tenn.
Camarata says "late talking," or talking after the age of 2, which affects about 10% of all toddlers, is an example.
"If late talking is now viewed as diagnostic for putting a child on 'the autism spectrum,' then all late talkers will be identified as autistic," Camarata says.
"This is important because, if there is nothing else wrong -- no other symptoms of autism or other disability such as cognitive impairment -- approximately 60%-70% of the late talkers catch up by the time they reach 3 years old," he tells WebMD.
Tracking Early Autism Diagnoses
For the study, researchers cross-referenced data on births in Massachusetts between 2001 and 2005 with records on children enrolled in the state's early-intervention programs for autism spectrum disorders before their third birthday.
The study included 385,631 children without documented autism spectrum disorders and 3,013 enrolled in early-intervention programs.
To be referred to an early-intervention program, children had to have failed a screening test of 23 questions called the modified checklist of autism in toddlers. The test asked questions about a child's ability to interact with others, pretend during play, walk, speak, and hear.
Information on parental characteristics like age, education level, and race, were derived from birth certificates.
Researchers also included information about whether the children were born prematurely or at low birth weights or whether they were single births or multiples.
Autism Incidence: Boys vs. Girls
The incidence of autism spectrum disorders in children less than 3 years of age increased from 56 per 10,000 in children born in 2001 to 93 per 10,000 in children born in 2005.
There was a greater increase in boys than in girls.
Among boys, the early autism diagnoses increased 70% between children born in 2001 and those born in 2005. They went up 39% in girls.
That means boys were about 4.5 times more likely than girls to be given an early diagnosis of autism spectrum disorder.
That's not a huge surprise, researchers say, given that autism is known to be about three to four times more prevalent in boys than in girls.
Low birth weights, premature births, and multiple births were all at increased risk of an early diagnosis of autism spectrum disorder, the study found.
Autism diagnoses were more likely in children born to older mothers, especially those over 45. A father's age or education appeared to have no impact on the likelihood of an autism diagnosis, however.
The study also found something intriguing with regards to race and ethnicity. At the beginning of the study, white children had a higher likelihood of early diagnosis. White children were nearly 30% more likely than African-American children and 90% more likely than Hispanic children to be referred to an early-intervention program. By the end of the study, those differences had disappeared.
"For a long time, it's been felt that minority children were out there at equal rates but we just weren't doing a good job of finding those children," Landa says.
The fact that rate of early diagnoses equalized by the end of the study, she says, suggests that outreach programs to minority communities are working.
Indeed, researchers say, all groups appear to be benefiting from greater public health efforts.
"The fact that we're getting them in early is great, because the earlier we can identify children and get them enrolled in appropriate services, the better the chances are to optimize their developmental and educational outcomes," Manning says.
SOURCES:
Manning, S. Pediatrics, online, May 16, 2011.
Robins, D. Journal of Autism and Development Disorders, 2001.
Rebecca Landa, PhD, director, Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore.
Susan E. Manning, MD, MPH, epidemiologist, CDC; Massachusetts Department of Public Health.
Sunday, May 22, 2011
Saturday, May 21, 2011
Rett Syndrome
Rett syndrome
Rett syndrome is a disorder of the nervous system that leads to developmental reversals, especially in the areas of expressive language and hand use.
Causes, incidence, and risk factors
Rett syndrome occurs almost exclusively in girls and may be misdiagnosed as autism or cerebral palsy.
Studies have linked many Rett syndrome cases to a defect in the methl-CpG-binding protein 2 (MeCP2) gene. This gene is on the X chromosome. Females have two X chromosomes, so even when one has this significant defect, the other X chromosome is normal enough for the child to survive.
Males born with this defective gene do not have a second X chromosome to make up for the problem. Therefore, the defect usually results in miscarriage, stillbirth, or very early death.
The condition affects about 1 out of 10,000 children. Groups of the disease have appeared within families and certain geographic regions, including Norway, Sweden, and northern Italy.
Symptoms
An infant with Rett syndrome usually has normal development for the first 6 - 18 months. Symptoms range from mild to severe.
Symptoms may include:
*
Apraxia
*
Breathing problems -- problems tend to get worse with stress; breathing is usually normal during sleep and abnormal while awake
*
Change in development
*
Excessive saliva and drooling
*
Floppy arms and legs -- frequently the first sign
*
Intellectual disabilities and learning difficulties (assessing cognitive skills in those with Rett syndrome, however, is difficult because of the speech and hand motion abnormalities)
*
Scoliosis
*
Shaky, unsteady, or stiff gait; or toe walking
*
Seizures
*
Slowing head growth beginning at approximately 5 - 6 months of age
*
Loss of normal sleep patterns
*
Loss of purposeful hand movements; for example, the grasp used to pick up small objects is replaced by repetitive hand motions like hand wringing or constant placement of hands in mouth
*
Loss of social engagement
*
Ongoing, severe constipation and gastroesophageal reflux (GERD)
*
Poor circulation that can lead to cold and bluish arms and legs
*
Severe language development problems
NOTE:
Problems in breathing pattern may be the most upsetting and difficult symptom for parents to watch. Why they happen and what to do about them is not well understood. Most experts in Rett syndrome recommend that parents remain calm through an episode of irregular breathing like breath holding. It may help to remind yourself that normal breathing always returns and that your child will become used to the abnormal breathing pattern.
Signs and tests
Genetic testing may be done to look for the gene defect associated with the syndrome. However, since the defect is not identified in everyone with the disease, the diagnosis of Rett syndrome is based on symptoms.
There are several different types of Rett syndrome:
*
Atypical
*
Classical (meets the diagnostic criteria)
*
Provisional (some symptoms appear between ages 1 and 3)
Rett syndrome is classified as atypical if:
*
It begins early (soon after birth) or late (beyond 18 months of age, sometimes as late as 3 or 4 years old)
*
Speech and hand skill problems are mild
*
It is appears in a boy (very rare)
Treatment
Treatment may include:
*
Assistance with feeding and diapering
*
Methods to treat constipation and GERD
*
Physical therapy to help prevent the hands from contracting
*
Weight bearing exercises for those with scoliosis
Supplemental feedings can help those with slowed growth. A feeding tube may be needed if the patient breathes in (aspirates) food. Diets high in calories and fat, as well as nasogastric tube feeds, can help increase weight and height. Weight gain may improve alertness and social interactions.
Medications such as carbamazepine may be used to treat seizures. Other medications or supplements that have been used or studied include:
*
Bromocriptine
*
Dextromethorphan
*
Folate and betaine
*
L-carnitine, which may help improve language skills, muscle mass, alertness, energy and quality of life while decreasing constipation and daytime sleepiness
*
L-dopa for motor rigidity in later stages of the disease
Stem cell therapy, alone or in combination with gene therapy, is another hopeful treatment.
Support Groups
International Rett Syndrome Association - www.rettsyndrome.org
Expectations (prognosis)
The disease slowly progresses until the patient is a teenager. Then, symptoms may improve. For example, seizures or breathing problems tend to lessen in late adolescence.
Developmental regression or delays vary. Usually, a child with Rett syndrome sits up properly but may not crawl. For those who do crawl, many do so by scooting on their tummy without using their hands.
Similarly, some children walk independently within the normal age range, while others are delayed, don't learn to walk independently at all, or don't learn to walk until late childhood or early adolescence. For those children who do learn to walk at the normal time, some keep that ability for their lifetime, while other children lose the skill.
Life expectancies are not well studied, although survival at least until the mid-20s is likely. The average life expectancy of a girl with Rett syndrome may be mid-40s. Death is often related to seizure, aspiration pneumonia, malnutrition, and accidents.
Calling your health care provider
Call your health care provider if you have any concerns about your child's development, if you notice a lack of normal development with motor or language skills in a child, or if there are associated disorders that need treatment.
Prevention
The likelihood of having another child with Rett syndrome is less than 1%.
References
1. Shah PE, Dalton R, Boris NW. Pervasive developmental disorders and childhood psychosis. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 29.
Review Date: 11/12/2010.
Reviewed by: Neil K. Kaneshiro, MD, MHA, Clinical Assistant Professor of Pediatrics, University of Washington School of Medicine. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
Source: Pubmed Health
Rett syndrome is a disorder of the nervous system that leads to developmental reversals, especially in the areas of expressive language and hand use.
Causes, incidence, and risk factors
Rett syndrome occurs almost exclusively in girls and may be misdiagnosed as autism or cerebral palsy.
Studies have linked many Rett syndrome cases to a defect in the methl-CpG-binding protein 2 (MeCP2) gene. This gene is on the X chromosome. Females have two X chromosomes, so even when one has this significant defect, the other X chromosome is normal enough for the child to survive.
Males born with this defective gene do not have a second X chromosome to make up for the problem. Therefore, the defect usually results in miscarriage, stillbirth, or very early death.
The condition affects about 1 out of 10,000 children. Groups of the disease have appeared within families and certain geographic regions, including Norway, Sweden, and northern Italy.
Symptoms
An infant with Rett syndrome usually has normal development for the first 6 - 18 months. Symptoms range from mild to severe.
Symptoms may include:
*
Apraxia
*
Breathing problems -- problems tend to get worse with stress; breathing is usually normal during sleep and abnormal while awake
*
Change in development
*
Excessive saliva and drooling
*
Floppy arms and legs -- frequently the first sign
*
Intellectual disabilities and learning difficulties (assessing cognitive skills in those with Rett syndrome, however, is difficult because of the speech and hand motion abnormalities)
*
Scoliosis
*
Shaky, unsteady, or stiff gait; or toe walking
*
Seizures
*
Slowing head growth beginning at approximately 5 - 6 months of age
*
Loss of normal sleep patterns
*
Loss of purposeful hand movements; for example, the grasp used to pick up small objects is replaced by repetitive hand motions like hand wringing or constant placement of hands in mouth
*
Loss of social engagement
*
Ongoing, severe constipation and gastroesophageal reflux (GERD)
*
Poor circulation that can lead to cold and bluish arms and legs
*
Severe language development problems
NOTE:
Problems in breathing pattern may be the most upsetting and difficult symptom for parents to watch. Why they happen and what to do about them is not well understood. Most experts in Rett syndrome recommend that parents remain calm through an episode of irregular breathing like breath holding. It may help to remind yourself that normal breathing always returns and that your child will become used to the abnormal breathing pattern.
Signs and tests
Genetic testing may be done to look for the gene defect associated with the syndrome. However, since the defect is not identified in everyone with the disease, the diagnosis of Rett syndrome is based on symptoms.
There are several different types of Rett syndrome:
*
Atypical
*
Classical (meets the diagnostic criteria)
*
Provisional (some symptoms appear between ages 1 and 3)
Rett syndrome is classified as atypical if:
*
It begins early (soon after birth) or late (beyond 18 months of age, sometimes as late as 3 or 4 years old)
*
Speech and hand skill problems are mild
*
It is appears in a boy (very rare)
Treatment
Treatment may include:
*
Assistance with feeding and diapering
*
Methods to treat constipation and GERD
*
Physical therapy to help prevent the hands from contracting
*
Weight bearing exercises for those with scoliosis
Supplemental feedings can help those with slowed growth. A feeding tube may be needed if the patient breathes in (aspirates) food. Diets high in calories and fat, as well as nasogastric tube feeds, can help increase weight and height. Weight gain may improve alertness and social interactions.
Medications such as carbamazepine may be used to treat seizures. Other medications or supplements that have been used or studied include:
*
Bromocriptine
*
Dextromethorphan
*
Folate and betaine
*
L-carnitine, which may help improve language skills, muscle mass, alertness, energy and quality of life while decreasing constipation and daytime sleepiness
*
L-dopa for motor rigidity in later stages of the disease
Stem cell therapy, alone or in combination with gene therapy, is another hopeful treatment.
Support Groups
International Rett Syndrome Association - www.rettsyndrome.org
Expectations (prognosis)
The disease slowly progresses until the patient is a teenager. Then, symptoms may improve. For example, seizures or breathing problems tend to lessen in late adolescence.
Developmental regression or delays vary. Usually, a child with Rett syndrome sits up properly but may not crawl. For those who do crawl, many do so by scooting on their tummy without using their hands.
Similarly, some children walk independently within the normal age range, while others are delayed, don't learn to walk independently at all, or don't learn to walk until late childhood or early adolescence. For those children who do learn to walk at the normal time, some keep that ability for their lifetime, while other children lose the skill.
Life expectancies are not well studied, although survival at least until the mid-20s is likely. The average life expectancy of a girl with Rett syndrome may be mid-40s. Death is often related to seizure, aspiration pneumonia, malnutrition, and accidents.
Calling your health care provider
Call your health care provider if you have any concerns about your child's development, if you notice a lack of normal development with motor or language skills in a child, or if there are associated disorders that need treatment.
Prevention
The likelihood of having another child with Rett syndrome is less than 1%.
References
1. Shah PE, Dalton R, Boris NW. Pervasive developmental disorders and childhood psychosis. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 29.
Review Date: 11/12/2010.
Reviewed by: Neil K. Kaneshiro, MD, MHA, Clinical Assistant Professor of Pediatrics, University of Washington School of Medicine. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
Source: Pubmed Health
Friday, April 22, 2011
The Difference Between Autism
By Lisa Jo Rudy, About.com Guide April 12, 2011
Yes, the grammatical error was intentional!
Autism Awareness Month is a great time to get out the word about issues in autism. One of the toughest for everyone, including people on the spectrum, parents, teachers, therapists and doctors, is the incredible disparity among people with autism. How do you make the world aware of a single disorder that can present itself so very differently in different individuals? How do you create policies, undertake research or provide services for a group of people who have radically different needs? How do you plan a school program, provide therapies, or even access support when your situation is practically unique?
Of course the answer is - there is no one "autism," and that issue lies at the heart of many of the problems experienced by members of the disparate group that is sometimes called the "autism community."
Some of the biggest differences we face include -
* Differences in physical symptoms. Some people with autism also have serious physical problems including (but not limited to) sensory dysfunctions, seizures, gastrointestinal problems, sleep issues and food allergies.
* Differences in functional level. One person with autism is brilliant, intense, extremely anxious and often depressed. Another is non-verbal and physically aggressive. A third is low-key, affectionate, verbal, but lacking in social and communication skills. Which of these people is most functional? The answer isn't always obvious. What is obvious is that these people can't do the same things, don't need the same supports, and have very little in common as individuals.
* Differences in onset of the disorder. Particularly for parents of children with autism, differences in personal experience can create huge rifts. While one parent saw her child "descend" into autism almost overnight, another sees that her son, who has always been different, is also an awful lot like Uncle Bill - the brilliant but quirky engineer. Differences like these are causing huge battles over questions like "what causes autism?," "can autism be prevented?" and "is autism a difference or a disability?"
So what are the different types of autism? How different are they from one another? Unfortunately, even the official categories of autism (there are five) don't make clear distinctions. And those categories will likely be reduced to just three when new guidelines for diagnosis are put in place in 2013. Here are some definitions, though, that may help families better understand "the difference between autism."
Types of Autism
What Are Pervasive Developmental Disorders?
"Pervasive Developmental Disorder" is a formal term that means exactly the same thing as the less formal "autism spectrum disorder." As with the autism spectrum, the group of disorders described as pervasive developmental disorders includes autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), Asperger syndrome, Childhood Disintegrative Disorder and Rett Syndrome.
What Is Asperger Syndrome?
Often called "the little professor" or "geek" syndrome, Asperger syndrome describes individuals at the highest-functioning end of the autism spectrum. Unlike other autism spectrum disorders, Asperger syndrome is often diagnosed in teens and adults. People with Asperger syndrome generally develop spoken language in the same way as typically developing children, but have issues with social communication that become more pronounced as they get older. Because people with Asperger syndrome are often very intelligent - but "quirky" - the disorder is sometimes nicknamed "geek syndrome" or "little professor syndrome."
What Is Mild Autism?
The term "mild autism" is not an official diagnosis. It's simply a more descriptive term than "Asperger syndrome" or "autism." Generally speaking, when people use the term mild autism they are referring to individuals whose symptoms fit an autism spectrum diagnosis, but who has strong verbal skills and few behavioral issues. Those individuals may, however, have significant problems with social communication. They may also have problems coping with too much sensory input (loud noise, bright lights, etc.).
What Is High Functioning Autism?
Like "mild" autism, high functioning autism (sometimes shortened to HFA) is a made-up term that's become more and more commonly used. HFA is a tricky term, because it can be hard to distinguish a person with HFA from a person with Asperger syndrome. The official distinction is that people with HFA had or have speech delays, while people with Asperger Syndrome have normal speech development. But there may also be very real differences in terms of social awareness, personality characteristics, and other traits. The jury is still debating the fine distinctions.
What Is PDD-NOS?
"Pervasive Developmental Disorder Not Otherwise Specified" is a mouthful of words that are often applied to people on the autism spectrum. It describes individuals who don't fully fit the criteria for other specific diagnoses, but are nevertheless autistic. Unfortunately, there is no easy way to define the symptoms of PDD-NOS, which may range from very mild to very severe. As a result, the term is rarely used outside of practioners' offices. Most parents, therapists and teachers prefer to use more descriptive (though less official) terms to describe their children, students and patients with PDD-NOS.
What Is Severe Autism (Autistic Disorder)?
Severe autism is officially termed autistic disorder. It goes by many other names, though, including profound autism, low functioning autism, or classic autism. People with autistic disorder are often non-verbal and intellectually disabled, and may have very challenging behaviors.
What Is Rett Syndrome?
Rett syndrome is a genetic disorder that affects only girls. It is the only one of the autism spectrum disorders that can be diagnosed medically (so far). Girls with Rett syndrome develop severe symptoms including the hallmark social communication challenges of autism. In addition, Rett syndrome can profoundly impair girls' ability to use their hands usefully.
Source: About.com
Yes, the grammatical error was intentional!
Autism Awareness Month is a great time to get out the word about issues in autism. One of the toughest for everyone, including people on the spectrum, parents, teachers, therapists and doctors, is the incredible disparity among people with autism. How do you make the world aware of a single disorder that can present itself so very differently in different individuals? How do you create policies, undertake research or provide services for a group of people who have radically different needs? How do you plan a school program, provide therapies, or even access support when your situation is practically unique?
Of course the answer is - there is no one "autism," and that issue lies at the heart of many of the problems experienced by members of the disparate group that is sometimes called the "autism community."
Some of the biggest differences we face include -
* Differences in physical symptoms. Some people with autism also have serious physical problems including (but not limited to) sensory dysfunctions, seizures, gastrointestinal problems, sleep issues and food allergies.
* Differences in functional level. One person with autism is brilliant, intense, extremely anxious and often depressed. Another is non-verbal and physically aggressive. A third is low-key, affectionate, verbal, but lacking in social and communication skills. Which of these people is most functional? The answer isn't always obvious. What is obvious is that these people can't do the same things, don't need the same supports, and have very little in common as individuals.
* Differences in onset of the disorder. Particularly for parents of children with autism, differences in personal experience can create huge rifts. While one parent saw her child "descend" into autism almost overnight, another sees that her son, who has always been different, is also an awful lot like Uncle Bill - the brilliant but quirky engineer. Differences like these are causing huge battles over questions like "what causes autism?," "can autism be prevented?" and "is autism a difference or a disability?"
So what are the different types of autism? How different are they from one another? Unfortunately, even the official categories of autism (there are five) don't make clear distinctions. And those categories will likely be reduced to just three when new guidelines for diagnosis are put in place in 2013. Here are some definitions, though, that may help families better understand "the difference between autism."
Types of Autism
What Are Pervasive Developmental Disorders?
"Pervasive Developmental Disorder" is a formal term that means exactly the same thing as the less formal "autism spectrum disorder." As with the autism spectrum, the group of disorders described as pervasive developmental disorders includes autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), Asperger syndrome, Childhood Disintegrative Disorder and Rett Syndrome.
What Is Asperger Syndrome?
Often called "the little professor" or "geek" syndrome, Asperger syndrome describes individuals at the highest-functioning end of the autism spectrum. Unlike other autism spectrum disorders, Asperger syndrome is often diagnosed in teens and adults. People with Asperger syndrome generally develop spoken language in the same way as typically developing children, but have issues with social communication that become more pronounced as they get older. Because people with Asperger syndrome are often very intelligent - but "quirky" - the disorder is sometimes nicknamed "geek syndrome" or "little professor syndrome."
What Is Mild Autism?
The term "mild autism" is not an official diagnosis. It's simply a more descriptive term than "Asperger syndrome" or "autism." Generally speaking, when people use the term mild autism they are referring to individuals whose symptoms fit an autism spectrum diagnosis, but who has strong verbal skills and few behavioral issues. Those individuals may, however, have significant problems with social communication. They may also have problems coping with too much sensory input (loud noise, bright lights, etc.).
What Is High Functioning Autism?
Like "mild" autism, high functioning autism (sometimes shortened to HFA) is a made-up term that's become more and more commonly used. HFA is a tricky term, because it can be hard to distinguish a person with HFA from a person with Asperger syndrome. The official distinction is that people with HFA had or have speech delays, while people with Asperger Syndrome have normal speech development. But there may also be very real differences in terms of social awareness, personality characteristics, and other traits. The jury is still debating the fine distinctions.
What Is PDD-NOS?
"Pervasive Developmental Disorder Not Otherwise Specified" is a mouthful of words that are often applied to people on the autism spectrum. It describes individuals who don't fully fit the criteria for other specific diagnoses, but are nevertheless autistic. Unfortunately, there is no easy way to define the symptoms of PDD-NOS, which may range from very mild to very severe. As a result, the term is rarely used outside of practioners' offices. Most parents, therapists and teachers prefer to use more descriptive (though less official) terms to describe their children, students and patients with PDD-NOS.
What Is Severe Autism (Autistic Disorder)?
Severe autism is officially termed autistic disorder. It goes by many other names, though, including profound autism, low functioning autism, or classic autism. People with autistic disorder are often non-verbal and intellectually disabled, and may have very challenging behaviors.
What Is Rett Syndrome?
Rett syndrome is a genetic disorder that affects only girls. It is the only one of the autism spectrum disorders that can be diagnosed medically (so far). Girls with Rett syndrome develop severe symptoms including the hallmark social communication challenges of autism. In addition, Rett syndrome can profoundly impair girls' ability to use their hands usefully.
Source: About.com
Monday, April 4, 2011
FAQ about the IGF-1 Rett Syndrome Trial
"Treatment of Rett Syndrome with IGF-1"
PI: Omar Khwaja MD, PhD
Frequently Asked Questions (FAQ)
Download a PDF version of these FAQ
Q: Who is eligible for this clinical trial?
A: Eligible participants will be girls between the ages of 2 and 12 years, have a positive MECP2 genetic test and reside in the United States for the duration of the study.
Q: My child has a mutation in CDKL5, can we still participate?
A: No; all the work that has contributed to the development of this study has been conducted in mice with mutations in MECP2. Therefore, we do not know what the effects will be on children with CDKL5 mutations and at this time we are not enrolling children with this condition.
Q: What is the difference between Phase 1 and Phase 2?
A: Phase 1: A total of 10 girls will be enrolled in Phase 1. The objective of Phase 1 is to determine the tolerability of IGF-1 in the Rett Syndrome population. The visit schedule for Phase 1 includes three 24-hour inpatient stays and three outpatient visits (lasting approximately 3 hours each). At the end of the fourth week, participants will come to the hospital for a day-long visit lasting approximately 8 hours. Subjects that choose to participate in Phase 1 will automatically be enrolled in Phase 2, where they will receive an additional 20 weeks of treatment with IGF-1.
Phase 2: Phase 2 is a placebo controlled study lasting a total of 50 weeks. 30 girls will be enrolled in this phase. Participants will receive treatment (either IGF-1 or placebo) for 20-weeks, followed by 20 weeks of the alternate treatment (for example, if a subject received placebo for the first 20 weeks, she will be treated with IGF-1 for the following 20 weeks). There is a 6-week break between the two 20-week increments, during which participants will receive no treatment. In Phase 2, parents are required to bring their child to Children's Hospital, Boston every 4 weeks throughout the duration of the study.
Q: How will children be selected for participation?
A: The complete "inclusion criteria" is listed in the consent forms which have been sent to families interested in enrolling their children in this study (Note: if you have not received these documents, please e-mail rettresearch@childrens.harvard.edu and we will forward these to you). If the number of children that meet criteria exceeds 40; the potential participants will be randomized and chosen by a lottery. We will notify parents if their child has been selected to confirm that they still wish to enroll.
Q: When will the children be selected?
A: Children will be enrolled steadily over the first year of the study.
Phase 1: Enrollment for this phase is currently closed. For those who have sent in applications for Phase 1, we will schedule screening visits in March 2011 and begin treating participants in April.
Phase 2: Enrollment for this phase is currently open. We anticipate starting screening for this phase in August 2011.
Q: How do I apply for participation in this study?
A: Please send an email to rettresearch@childrens.harvard.edu and we will send you the necessary information and forms for enrollment.
Q: Once selections are made, will a more defined schedule of visits be provided?
A: Yes; at enrollment you will select a schedule schema. Once the first visit has occurred, this schedule is "set in stone" and cannot be altered under any circumstances.
Q: How soon after the initial screening/visits will the trial begin?
A: This will depend on you and your family's schedule. You may select when you would like the visits to begin.
Q: Can people outside of the Northeast enroll in Phase 1?
A: While Phase 1 is open to anyone, those who choose to enroll will most likely reside in the New England area as participants are required to visit the hospital twice a week for safety monitoring.
Q: If we choose not to participate in Phase 1, will this reduce our daughter's chance of being chosen for Phase 2?
A: No; participation in Phase 1 will in no way affect her eligibility for Phase 2.
Q: If I do not get selected for Phase 1, do I have to apply again for Phase 2?
A: No, the girls that are not selected for Phase 1 will automatically roll-over for enrollment in Phase 2.
Q: Can I go to my local Rett syndrome clinic for the evaluations?
A: No; the only site approved for clinical evaluations is Children's Hospital Boston.
Q: I tried to sign the consent forms, but they say "Not Valid"; now what?
A: These consent forms are intended for your review only. The official consent form will be signed in-person after your daughter has been selected and you have met with the research team to confirm her eligibility.
Q: Is there a hotel close to the hospital?
A: Yes, the closest hotel, the Inn at Longwood Medical, is next door to the hospital.
Q: Are there any discounted rates on airfare or hotel stay if you are traveling with a special needs child that is receiving treatment in a hospital setting such as this trial?
A: For airfare, check out Miracle Flights for Kids or Angel Flight. For families that cannot afford a hotel, there are a handful of rooms resourced within the hospital. However, these rooms are only available on a first-come, first-served basis and cannot be reserved well in advance. Unfortunately, we are not able to compensate families for lodging or travel.
For further information about this study, please contact:
Phone: 617-355-5230
Fax: 617-730-4669
Email: rettresearch@childrens.harvard.edu
Source: Children's Hospital Boston
PI: Omar Khwaja MD, PhD
Frequently Asked Questions (FAQ)
Download a PDF version of these FAQ
Q: Who is eligible for this clinical trial?
A: Eligible participants will be girls between the ages of 2 and 12 years, have a positive MECP2 genetic test and reside in the United States for the duration of the study.
Q: My child has a mutation in CDKL5, can we still participate?
A: No; all the work that has contributed to the development of this study has been conducted in mice with mutations in MECP2. Therefore, we do not know what the effects will be on children with CDKL5 mutations and at this time we are not enrolling children with this condition.
Q: What is the difference between Phase 1 and Phase 2?
A: Phase 1: A total of 10 girls will be enrolled in Phase 1. The objective of Phase 1 is to determine the tolerability of IGF-1 in the Rett Syndrome population. The visit schedule for Phase 1 includes three 24-hour inpatient stays and three outpatient visits (lasting approximately 3 hours each). At the end of the fourth week, participants will come to the hospital for a day-long visit lasting approximately 8 hours. Subjects that choose to participate in Phase 1 will automatically be enrolled in Phase 2, where they will receive an additional 20 weeks of treatment with IGF-1.
Phase 2: Phase 2 is a placebo controlled study lasting a total of 50 weeks. 30 girls will be enrolled in this phase. Participants will receive treatment (either IGF-1 or placebo) for 20-weeks, followed by 20 weeks of the alternate treatment (for example, if a subject received placebo for the first 20 weeks, she will be treated with IGF-1 for the following 20 weeks). There is a 6-week break between the two 20-week increments, during which participants will receive no treatment. In Phase 2, parents are required to bring their child to Children's Hospital, Boston every 4 weeks throughout the duration of the study.
Q: How will children be selected for participation?
A: The complete "inclusion criteria" is listed in the consent forms which have been sent to families interested in enrolling their children in this study (Note: if you have not received these documents, please e-mail rettresearch@childrens.harvard.edu and we will forward these to you). If the number of children that meet criteria exceeds 40; the potential participants will be randomized and chosen by a lottery. We will notify parents if their child has been selected to confirm that they still wish to enroll.
Q: When will the children be selected?
A: Children will be enrolled steadily over the first year of the study.
Phase 1: Enrollment for this phase is currently closed. For those who have sent in applications for Phase 1, we will schedule screening visits in March 2011 and begin treating participants in April.
Phase 2: Enrollment for this phase is currently open. We anticipate starting screening for this phase in August 2011.
Q: How do I apply for participation in this study?
A: Please send an email to rettresearch@childrens.harvard.edu and we will send you the necessary information and forms for enrollment.
Q: Once selections are made, will a more defined schedule of visits be provided?
A: Yes; at enrollment you will select a schedule schema. Once the first visit has occurred, this schedule is "set in stone" and cannot be altered under any circumstances.
Q: How soon after the initial screening/visits will the trial begin?
A: This will depend on you and your family's schedule. You may select when you would like the visits to begin.
Q: Can people outside of the Northeast enroll in Phase 1?
A: While Phase 1 is open to anyone, those who choose to enroll will most likely reside in the New England area as participants are required to visit the hospital twice a week for safety monitoring.
Q: If we choose not to participate in Phase 1, will this reduce our daughter's chance of being chosen for Phase 2?
A: No; participation in Phase 1 will in no way affect her eligibility for Phase 2.
Q: If I do not get selected for Phase 1, do I have to apply again for Phase 2?
A: No, the girls that are not selected for Phase 1 will automatically roll-over for enrollment in Phase 2.
Q: Can I go to my local Rett syndrome clinic for the evaluations?
A: No; the only site approved for clinical evaluations is Children's Hospital Boston.
Q: I tried to sign the consent forms, but they say "Not Valid"; now what?
A: These consent forms are intended for your review only. The official consent form will be signed in-person after your daughter has been selected and you have met with the research team to confirm her eligibility.
Q: Is there a hotel close to the hospital?
A: Yes, the closest hotel, the Inn at Longwood Medical, is next door to the hospital.
Q: Are there any discounted rates on airfare or hotel stay if you are traveling with a special needs child that is receiving treatment in a hospital setting such as this trial?
A: For airfare, check out Miracle Flights for Kids or Angel Flight. For families that cannot afford a hotel, there are a handful of rooms resourced within the hospital. However, these rooms are only available on a first-come, first-served basis and cannot be reserved well in advance. Unfortunately, we are not able to compensate families for lodging or travel.
For further information about this study, please contact:
Phone: 617-355-5230
Fax: 617-730-4669
Email: rettresearch@childrens.harvard.edu
Source: Children's Hospital Boston
Wednesday, March 30, 2011
Research funding a distant dream for less 'popular' diseases: Less 'popular' diseases not seeing proper contributions
By AMY NEFF ROTH
Observer-Dispatch
Posted Mar 28, 2011 @ 05:00 AM
Three-year-old Raymond Gallo might not be able to walk or hear without a weekly dose of intravenous medicine that attacks the effects of Hunter syndrome, a rare genetic disease. But thanks to that medicine, Raymond can watch and hear his favorite TV shows – “Dora,” “Diego” and “iCarly” – walk up to a baby to say hi or walk over to his mom for a hug. Just don’t ask him to walk outside in the winter; Raymond, who lives in Boonville, hates the snow.
Before Raymond’s medicine was approved by the federal Food and Drug Administration in 2006, most early-onset Hunter syndrome patients like him died between the ages of 10 and 20. As things stand, Raymond’s prognosis is uncertain.
Every year, thousands of area residents turn out to raise money for medical research at events such as America’s Greatest Heart Run & Walk or the American Cancer Society’s Relay for Life. These events give private citizens the ability to vote, with their feet, on where the billions of dollars the United States invests in medical research each year should go.
Many choose causes based on their history with a disease – as survivors, caregivers, loved ones or friends.
Some have been touched by stories in the media, some by the involvement of a celebrity such as Christopher Reeve or Michael J. Fox.
But it’s much harder to find advocates for kids such as Raymond; Hunter syndrome and 6,000 other so-called orphan diseases affect fewer than 200,000 Americans each.
So while Americans invested $139 billion into medical research in 2009, as estimated by the nonprofit Research!America, treatments and cures remain a distant dream for patients with less “popular” diseases.
There simply isn’t enough money to go around.
Money for research comes from many sources: private industry, the largest contributor; the federal government, especially the National Institutes of Health; local and state governments; private foundations; and the health care nonprofits for which residents walk, run and jump rope to raise money.
Each group has its own decision-making process, but it always involves scientists judging the merits of research proposals. No one wants to invest in unsuccessful or insignificant research.
“My perspective is that our current way of funding medical research in the U.S. resembles Winston Churchill’s quote about democracy, (that) it’s the worst form of government in the world, except for all the others,” said Dr. Patrick McNulty, chief of cardiology at Bassett Medical Center in Cooperstown, and a former researcher who reviews research grants for the American Heart Association and the National Institutes of Health.
The system would be hard to improve, agreed Jonathan Moreno, professor of medical ethics and of the history and sociology of science at the University of Pennsylvania in Philadelphia. “The fact is that there is no completely objective metric,” he said.
Buying hope
Research money doesn’t just buy better treatments: It buys hope for patients with incurable diseases and their families.
Raymond’s parents, Jennifer and Richard, are praying that his “miracle” medicine – administered over the course of five hours every Monday – will save him until researchers can find a cure.
The Gallos’ concern isn’t just for Raymond; their daughter Kaitlin, 7, could be a carrier of the Hunter gene.
Patients with Hunter syndrome, most often boys, lack an enzyme that helps them break down certain kinds of sugar which then build up in the body. There is a milder late-onset form, but for early onset patients such as Raymond, symptoms can include aggressive behavior, hyperactivity, mental retardation, spasticity, coarse facial features, progressive deafness, carpal tunnel syndrome, joint stiffness and a large head.
As an infant, Raymond was happy, but just wasn’t hitting developmental milestones, Jennifer said. But his pediatrician kept insisting everything was OK. A new doctor diagnosed him when he was just over a year old.
The couple, both teachers, hasn’t put in long hours researching their son’s condition, as some families do.
“If you look online, it’s very scary,” Jennifer said.
“I know enough that it would make me crazy,” Richard added.
Instead, the couple stays in touch with experts they trust for information, they said.
Developments in the human genome, nanotechnology and stem cell research have given scientists wonderful opportunities to make new discoveries, said Steven Goodman, vice president for research and dean of the College of Graduate Studies at Upstate Medical University in Syracuse.
“I personally think we’re at a place where progress could be made at an unprecedented rate,” he said.
That can’t happen, though, without more investment in research, Goodman said.
Meanwhile, the House of Representatives has passed a bill that would cut the NIH’s budget this year by $1.6 billion, or 5.2 percent.
Cause celebre
Science is not the only factor affecting research funding. Other factors creep in, too: politics, campaigns by health-related advocacy groups, celebrity spokespeople, lobbying, public opinion and profits. Just think of those ubiquitous pink ribbons and Jerry Lewis’ telethon.
Dr. Charles Antzelevitch, executive director and director of research for Masonic Medical Research Laboratory in Utica, said he’s been working with pharmaceutical companies for 15 years to develop drugs for the rare, but potentially fatal genetic cardiac arrhythmias he researches. But Antzelevitch said he’s been disappointed by the lack of industry focus.
“The profit margin is not there,” he said.
Raymond’s disease might once have been overlooked by drug companies. But the Orphan Drug Act of 1983 gave special encouragements to drug makers to develop treatments for orphan diseases such as Hunter syndrome, which affect fewer than 200,000 Americans. In the decade before the program began, fewer than 10 “orphan drugs” were approved, according to the FDA. Since 1983, 366 have been approved.
But profits aren’t Antzelevitch’s only concern with the funding system.
“We get very concerned when we see the National Institutes of Health, for example, having dictates from Congress based on these lobbying efforts by celebrities, and so forth, and individual lobbying groups,” he said. “It’s important to be responsive to the populace, but you really need to put the money where it can advance science in a meaningful way, and it’s the scientific community, I think, that can best judge where the money can do the most good.”
But for Goodman, celebrity involvement, advocacy campaigns and anything else that brings attention to medical research is good. The field can use all the attention – and funding – it can get, he said.
And more celebrities are taking the time to sit down with scientists to learn how they can help, forging an alliance that can create positive awareness, Moreno said. But not always; Patrick Swayze’s death from pancreatic cancer in 2009 did not seem to bring the disease to the fore.
It’s hard, Moreno said, to figure out why some diseases get more attention and funding than others.
Mary Shulsky, of Deerfield, thinks so, too. Her husband, John, 66, and his “big brother,” identical twin Jim, who was born three minutes earlier, were diagnosed with pancreatic cancer during the same week in early September.
The NIH keeps track of its annual funding in 229 research categories in which Congress has shown an interest historically. Seven organ cancers are on the list. Pancreatic is not.
John was diagnosed as stage four, and given six months to a year to live; his cancer counts were way down mid-month, which is keeping him optimistic, he said.
Jim, of Whitesboro, is stage two. An avid outdoorsman, Jim said the diagnosis came out of the blue “because you don’t hear about it. All you do is hear is about the other types.”
Pancreatic cancer has the lowest survival rate of any cancer – less than 6 percent at the five-year mark – because it is most often diagnosed in the late stages. There is no screening test and there are few early-stage symptoms. Jim lucked out in a sense because a tumor blocking his bile duct gave him early symptoms.
John wasn’t so lucky. He and Mary had planned on traveling after retirement, but John kept putting off retirement because he loved his job at Indium Corp.’s plant in Utica, Mary said. In fact he’s still officially an employee out on disability, she said.
Mary remembers the moment John’s doctor broke the news.
“I knew when we sat down. I could tell by the look on his face. He said, ‘I’m very sorry. It’s cancer,’” she recalled.
“All of our plans and hopes and dreams …,” she began, before choking up, unable to go on.
“It was devastating. I just can’t describe it.”
And now Mary also is concerned for her two children and two nephews because of the family’s evident genetic link to the cancer.
“We just keep hoping for a miracle,” Mary said. “There are only 37,000 people that die of this every year, and it’s not enough for them to get the funding that they need to do the research, like breast cancer. They get all kinds of funding.”
Copyright 2011 The Observer-Dispatch, Utica, New York. Some rights reserved
Observer-Dispatch
Posted Mar 28, 2011 @ 05:00 AM
Three-year-old Raymond Gallo might not be able to walk or hear without a weekly dose of intravenous medicine that attacks the effects of Hunter syndrome, a rare genetic disease. But thanks to that medicine, Raymond can watch and hear his favorite TV shows – “Dora,” “Diego” and “iCarly” – walk up to a baby to say hi or walk over to his mom for a hug. Just don’t ask him to walk outside in the winter; Raymond, who lives in Boonville, hates the snow.
Before Raymond’s medicine was approved by the federal Food and Drug Administration in 2006, most early-onset Hunter syndrome patients like him died between the ages of 10 and 20. As things stand, Raymond’s prognosis is uncertain.
Every year, thousands of area residents turn out to raise money for medical research at events such as America’s Greatest Heart Run & Walk or the American Cancer Society’s Relay for Life. These events give private citizens the ability to vote, with their feet, on where the billions of dollars the United States invests in medical research each year should go.
Many choose causes based on their history with a disease – as survivors, caregivers, loved ones or friends.
Some have been touched by stories in the media, some by the involvement of a celebrity such as Christopher Reeve or Michael J. Fox.
But it’s much harder to find advocates for kids such as Raymond; Hunter syndrome and 6,000 other so-called orphan diseases affect fewer than 200,000 Americans each.
So while Americans invested $139 billion into medical research in 2009, as estimated by the nonprofit Research!America, treatments and cures remain a distant dream for patients with less “popular” diseases.
There simply isn’t enough money to go around.
Money for research comes from many sources: private industry, the largest contributor; the federal government, especially the National Institutes of Health; local and state governments; private foundations; and the health care nonprofits for which residents walk, run and jump rope to raise money.
Each group has its own decision-making process, but it always involves scientists judging the merits of research proposals. No one wants to invest in unsuccessful or insignificant research.
“My perspective is that our current way of funding medical research in the U.S. resembles Winston Churchill’s quote about democracy, (that) it’s the worst form of government in the world, except for all the others,” said Dr. Patrick McNulty, chief of cardiology at Bassett Medical Center in Cooperstown, and a former researcher who reviews research grants for the American Heart Association and the National Institutes of Health.
The system would be hard to improve, agreed Jonathan Moreno, professor of medical ethics and of the history and sociology of science at the University of Pennsylvania in Philadelphia. “The fact is that there is no completely objective metric,” he said.
Buying hope
Research money doesn’t just buy better treatments: It buys hope for patients with incurable diseases and their families.
Raymond’s parents, Jennifer and Richard, are praying that his “miracle” medicine – administered over the course of five hours every Monday – will save him until researchers can find a cure.
The Gallos’ concern isn’t just for Raymond; their daughter Kaitlin, 7, could be a carrier of the Hunter gene.
Patients with Hunter syndrome, most often boys, lack an enzyme that helps them break down certain kinds of sugar which then build up in the body. There is a milder late-onset form, but for early onset patients such as Raymond, symptoms can include aggressive behavior, hyperactivity, mental retardation, spasticity, coarse facial features, progressive deafness, carpal tunnel syndrome, joint stiffness and a large head.
As an infant, Raymond was happy, but just wasn’t hitting developmental milestones, Jennifer said. But his pediatrician kept insisting everything was OK. A new doctor diagnosed him when he was just over a year old.
The couple, both teachers, hasn’t put in long hours researching their son’s condition, as some families do.
“If you look online, it’s very scary,” Jennifer said.
“I know enough that it would make me crazy,” Richard added.
Instead, the couple stays in touch with experts they trust for information, they said.
Developments in the human genome, nanotechnology and stem cell research have given scientists wonderful opportunities to make new discoveries, said Steven Goodman, vice president for research and dean of the College of Graduate Studies at Upstate Medical University in Syracuse.
“I personally think we’re at a place where progress could be made at an unprecedented rate,” he said.
That can’t happen, though, without more investment in research, Goodman said.
Meanwhile, the House of Representatives has passed a bill that would cut the NIH’s budget this year by $1.6 billion, or 5.2 percent.
Cause celebre
Science is not the only factor affecting research funding. Other factors creep in, too: politics, campaigns by health-related advocacy groups, celebrity spokespeople, lobbying, public opinion and profits. Just think of those ubiquitous pink ribbons and Jerry Lewis’ telethon.
Dr. Charles Antzelevitch, executive director and director of research for Masonic Medical Research Laboratory in Utica, said he’s been working with pharmaceutical companies for 15 years to develop drugs for the rare, but potentially fatal genetic cardiac arrhythmias he researches. But Antzelevitch said he’s been disappointed by the lack of industry focus.
“The profit margin is not there,” he said.
Raymond’s disease might once have been overlooked by drug companies. But the Orphan Drug Act of 1983 gave special encouragements to drug makers to develop treatments for orphan diseases such as Hunter syndrome, which affect fewer than 200,000 Americans. In the decade before the program began, fewer than 10 “orphan drugs” were approved, according to the FDA. Since 1983, 366 have been approved.
But profits aren’t Antzelevitch’s only concern with the funding system.
“We get very concerned when we see the National Institutes of Health, for example, having dictates from Congress based on these lobbying efforts by celebrities, and so forth, and individual lobbying groups,” he said. “It’s important to be responsive to the populace, but you really need to put the money where it can advance science in a meaningful way, and it’s the scientific community, I think, that can best judge where the money can do the most good.”
But for Goodman, celebrity involvement, advocacy campaigns and anything else that brings attention to medical research is good. The field can use all the attention – and funding – it can get, he said.
And more celebrities are taking the time to sit down with scientists to learn how they can help, forging an alliance that can create positive awareness, Moreno said. But not always; Patrick Swayze’s death from pancreatic cancer in 2009 did not seem to bring the disease to the fore.
It’s hard, Moreno said, to figure out why some diseases get more attention and funding than others.
Mary Shulsky, of Deerfield, thinks so, too. Her husband, John, 66, and his “big brother,” identical twin Jim, who was born three minutes earlier, were diagnosed with pancreatic cancer during the same week in early September.
The NIH keeps track of its annual funding in 229 research categories in which Congress has shown an interest historically. Seven organ cancers are on the list. Pancreatic is not.
John was diagnosed as stage four, and given six months to a year to live; his cancer counts were way down mid-month, which is keeping him optimistic, he said.
Jim, of Whitesboro, is stage two. An avid outdoorsman, Jim said the diagnosis came out of the blue “because you don’t hear about it. All you do is hear is about the other types.”
Pancreatic cancer has the lowest survival rate of any cancer – less than 6 percent at the five-year mark – because it is most often diagnosed in the late stages. There is no screening test and there are few early-stage symptoms. Jim lucked out in a sense because a tumor blocking his bile duct gave him early symptoms.
John wasn’t so lucky. He and Mary had planned on traveling after retirement, but John kept putting off retirement because he loved his job at Indium Corp.’s plant in Utica, Mary said. In fact he’s still officially an employee out on disability, she said.
Mary remembers the moment John’s doctor broke the news.
“I knew when we sat down. I could tell by the look on his face. He said, ‘I’m very sorry. It’s cancer,’” she recalled.
“All of our plans and hopes and dreams …,” she began, before choking up, unable to go on.
“It was devastating. I just can’t describe it.”
And now Mary also is concerned for her two children and two nephews because of the family’s evident genetic link to the cancer.
“We just keep hoping for a miracle,” Mary said. “There are only 37,000 people that die of this every year, and it’s not enough for them to get the funding that they need to do the research, like breast cancer. They get all kinds of funding.”
Copyright 2011 The Observer-Dispatch, Utica, New York. Some rights reserved
Monday, March 21, 2011
Breakthrough in delivering drugs to the brain
By James Gallagher Health reporter, BBC News
A new way of delivering drugs to the brain has been developed by scientists at the University of Oxford.
They used the body's own transporters - exosomes - to deliver drugs in an experiment on mice.
The authors say the study, in Nature Biotechnology, could be vital for treating diseases such as Alzheimer's, Parkinson's and Muscular Dystrophy.
The Alzheimer's Society said the study was "exciting" and could lead to more effective treatments.
Research barrier
One of the medical challenges with diseases of the brain is getting any treatment to cross the blood-brain barrier.
The barrier exists to protect the brain, preventing bacteria from crossing over from the blood, while letting oxygen through.
However, this has also produced problems for medicine, as drugs can also be blocked.
In this study the researchers used exosomes to cross that barrier.
Exosomes are like the body's own fleet of incredibly small vans, transporting materials between cells.
The team at Oxford harvested exosomes from mouse dentritic cells, part of the immune system, which naturally produce large numbers of exosomes.
They then fused the exosomes with targeting proteins from the rabies virus, which binds to acetylcholine receptors in brain cells, so the exosome would target the brain.
They filled the exosomes with a piece of genetic code, siRNA, and injected them back into the mice.
The siRNA was delivered to the brain cells and turned off a gene, BACE1, which is involved in Alzheimer's disease.
The authors reported a 60% reduction in the gene's activity.
"These are dramatic and exciting results" said the lead researcher Dr Matthew Wood.
"This is the first time this natural system has been exploited for drug delivery."
Customised
The research group believes that the method could modified to treat other conditions and other parts of the body.
Dr Wood said: "We are working on sending exosomes to muscle, but you can envisage targeting any tissue.
"It can also be made specific by changing the drug used."
The researchers are now going to test the treatment on mice with Alzheimer's disease to see if their condition changes.
The team expect to begin trials in human patients within five years.
Dr Susanne Sorensen, head of research at the Alzheimer's Society, said: "In this exciting study, researchers may have overcome a major barrier to the delivery of potential new drugs for many neurological diseases including Alzheimer's.
She said the blood-brain barrier had been an "enormous issue as many potential drugs have not been properly tested because you couldn't get enough of them into the brain."
She added: "If this delivery method proves safe in humans, then we may see more effective drugs being made available for people with Alzheimer's in the future."
Dr Simon Ridley, head of research at Alzheimer's Research UK, said: "This is innovative research, but at such an early stage it's still a long way from becoming a treatment for patients.
"Designing drugs that cross the blood brain barrier is a key goal of research that holds the promise of improving the effectiveness of Alzheimer's treatments in the future."
Source: BBC News
A new way of delivering drugs to the brain has been developed by scientists at the University of Oxford.
They used the body's own transporters - exosomes - to deliver drugs in an experiment on mice.
The authors say the study, in Nature Biotechnology, could be vital for treating diseases such as Alzheimer's, Parkinson's and Muscular Dystrophy.
The Alzheimer's Society said the study was "exciting" and could lead to more effective treatments.
Research barrier
One of the medical challenges with diseases of the brain is getting any treatment to cross the blood-brain barrier.
The barrier exists to protect the brain, preventing bacteria from crossing over from the blood, while letting oxygen through.
However, this has also produced problems for medicine, as drugs can also be blocked.
In this study the researchers used exosomes to cross that barrier.
Exosomes are like the body's own fleet of incredibly small vans, transporting materials between cells.
The team at Oxford harvested exosomes from mouse dentritic cells, part of the immune system, which naturally produce large numbers of exosomes.
They then fused the exosomes with targeting proteins from the rabies virus, which binds to acetylcholine receptors in brain cells, so the exosome would target the brain.
They filled the exosomes with a piece of genetic code, siRNA, and injected them back into the mice.
The siRNA was delivered to the brain cells and turned off a gene, BACE1, which is involved in Alzheimer's disease.
The authors reported a 60% reduction in the gene's activity.
"These are dramatic and exciting results" said the lead researcher Dr Matthew Wood.
"This is the first time this natural system has been exploited for drug delivery."
Customised
The research group believes that the method could modified to treat other conditions and other parts of the body.
Dr Wood said: "We are working on sending exosomes to muscle, but you can envisage targeting any tissue.
"It can also be made specific by changing the drug used."
The researchers are now going to test the treatment on mice with Alzheimer's disease to see if their condition changes.
The team expect to begin trials in human patients within five years.
Dr Susanne Sorensen, head of research at the Alzheimer's Society, said: "In this exciting study, researchers may have overcome a major barrier to the delivery of potential new drugs for many neurological diseases including Alzheimer's.
She said the blood-brain barrier had been an "enormous issue as many potential drugs have not been properly tested because you couldn't get enough of them into the brain."
She added: "If this delivery method proves safe in humans, then we may see more effective drugs being made available for people with Alzheimer's in the future."
Dr Simon Ridley, head of research at Alzheimer's Research UK, said: "This is innovative research, but at such an early stage it's still a long way from becoming a treatment for patients.
"Designing drugs that cross the blood brain barrier is a key goal of research that holds the promise of improving the effectiveness of Alzheimer's treatments in the future."
Source: BBC News
Wednesday, March 16, 2011
April is World's Autism Awareness Month
April is Autism Awareness Month, and April 2nd is International Autism Awareness Day. Please wear blue clour to raise awareness about autism and spread the word by educating others.
For more information on Autism Awareness, please click on the title
For more information on Autism Awareness, please click on the title
Thursday, February 24, 2011
Repairing faulty genes
22 February 2011
Israeli scientists have developed compounds that could be better treatments for genetic diseases than current drugs.
Timor Baasov and his colleagues at the Israel Institute of Technology have improved compounds used to suppress faults in genes called nonsense mutations.
Nonsense mutations, which cause more than 1800 human diseases, are alterations in the genetic code that stop protein production prematurely, leading to truncated or nonfunctional proteins. Gene therapy is one treatment, but it's had limited success. With suppression therapy, small molecules allow cells' protein producing equipment to skip over nonsense mutations to restore the proteins. Aminoglycosides - antibiotic amine-modified sugars - are the only clinically available drug family known to be effective in suppression therapy, but at effective doses, the compounds have high human toxicity.
To reduce the toxicity, the team introduced a methyl group onto two aminoglycosides. They tested the new derivatives in an in vitro suppression test on six different nonsense mutations for different diseases and carried out toxicity tests on human cells. They found that the compounds exhibited significantly improved activity and reduced toxicity compared to gentamicin, an aminoglycoside antibiotic used to treat bacterial infections.
'Treating genetic disorders is one of the biggest challenges of modern medicine. The likelihood that suppression therapy could be used clinically is very feasible,' says Baasov.
'The data emphasise the enormous potential of modified aminoglycosides for [nonsense suppression] therapy to combat nonsense mutation-based disorders with limited or no current therapeutic options,' says Uwe Wolfrum, a cell biologist at the Johannes Gutenberg University of Mainz, Germany. 'This raises hope for future clinical trials.'
'Our lead compounds are under intensive examination on numerous genetic disease models including cystic fibrosis, Hurler syndrome, Rett syndrome and Usher syndrome,' concludes Baasov.
Amaya Camara-Campos
Source: RSC
Note: To read original post click on the title of the post.
Israeli scientists have developed compounds that could be better treatments for genetic diseases than current drugs.
Timor Baasov and his colleagues at the Israel Institute of Technology have improved compounds used to suppress faults in genes called nonsense mutations.
Nonsense mutations, which cause more than 1800 human diseases, are alterations in the genetic code that stop protein production prematurely, leading to truncated or nonfunctional proteins. Gene therapy is one treatment, but it's had limited success. With suppression therapy, small molecules allow cells' protein producing equipment to skip over nonsense mutations to restore the proteins. Aminoglycosides - antibiotic amine-modified sugars - are the only clinically available drug family known to be effective in suppression therapy, but at effective doses, the compounds have high human toxicity.
To reduce the toxicity, the team introduced a methyl group onto two aminoglycosides. They tested the new derivatives in an in vitro suppression test on six different nonsense mutations for different diseases and carried out toxicity tests on human cells. They found that the compounds exhibited significantly improved activity and reduced toxicity compared to gentamicin, an aminoglycoside antibiotic used to treat bacterial infections.
'Treating genetic disorders is one of the biggest challenges of modern medicine. The likelihood that suppression therapy could be used clinically is very feasible,' says Baasov.
'The data emphasise the enormous potential of modified aminoglycosides for [nonsense suppression] therapy to combat nonsense mutation-based disorders with limited or no current therapeutic options,' says Uwe Wolfrum, a cell biologist at the Johannes Gutenberg University of Mainz, Germany. 'This raises hope for future clinical trials.'
'Our lead compounds are under intensive examination on numerous genetic disease models including cystic fibrosis, Hurler syndrome, Rett syndrome and Usher syndrome,' concludes Baasov.
Amaya Camara-Campos
Source: RSC
Note: To read original post click on the title of the post.
Friday, February 18, 2011
Licence rules hinder work on rare disease
Animal model off-limits to Rett-syndrome researchers.
Stashed away somewhere in a freezer in Cambridge, Massachusetts, is a mouse embryo that Etienne Joly would dearly like to get his hands on.
Joly is an immunologist based in Toulouse, France, with a keen interest in Rett syndrome, an incurable and debilitating disease that almost exclusively affects young girls. The mouse, developed by a team at the Novartis Institutes for Biomedical Research in Cambridge, carries a fluorescently tagged version of the gene that is mutated in the disease. It is the perfect tool, Joly says, for testing an idea he has about Rett syndrome. But a thicket of legal restrictions puts the mouse off-limits to anyone outside Novartis, even though scientists at the company are no longer using the model in their work on Rett syndrome.
"All scientists and families are asking for is the right to look into this disease and to try to understand it better," says Joly, who has embarked on a letter-writing campaign against the restrictions. "And when you know that there is a tool, but you can't use it because some lawyer says that you can't have the materials, then you get angry." Scientists and experts in intellectual-property issues say that the case shows how science can be impeded when onerous licensing rules govern the sharing of research materials.
Girls with Rett syndrome are healthy as babies, then progressively lose the ability to speak, move, eat and breathe normally. Because the disease is rare, affecting just one in 10,000 to 20,000 girls, it is an unattractive target for drug companies. Academic researchers have picked up the slack, and the field has moved at breakneck speed in recent years, from the 1999 discovery that defects in the gene MECP2 cause the disease, to clinical trials of possible treatments today.
Yet no one knows how the mutation causes the disease. A few years ago, Joly, who works at the Institute of Pharmacology and Structural Biology, came up with what he calls a "slightly unconventional" idea that the Rett-syndrome gene might have a role in regulating immune responses in the central nervous system. To explore his hypothesis, Joly needed an animal model that would allow him to trace where the gene is expressed.
In 2008, Joly learned about the engineered mouse. Led by molecular biologist Cecile Blaustein, the Novartis team had joined a copy of the mouse Mecp2 gene to a copy of the gene that makes enhanced green fluorescent protein (EGFP) to produce an animal in which the gene's activity can be traced throughout the brain and body (R. S. Schmid et al. Neuroreport 19, 393–398; 2008).
But after three years of trying, neither Joly nor any other Rett-syndrome researcher has been able to gain access to the mouse. When researchers asked to share it, Blaustein and her colleagues said that they would have liked to but couldn't because of the terms of Novartis's licence on EGFP, which it obtained from GE Healthcare.
Novartis and GE have been unable to negotiate a way to share the mice, says Jeff Lockwood, spokesman for the Novartis Institutes for Biomedical Research — even though Novartis has ended its research project on the mice.
When Monica Coenraads, executive director of the Rett Syndrome Research Trust in Trumbull, Connecticut, tried to broker an agreement to share the mice, GE and Novartis asked the US National Institutes of Health (NIH) in Bethesda, Maryland, to distribute the mice through its Mutant Mouse Regional Resource Centers. But Lili Portilla, senior adviser for technology transfer at the NIH National Center for Research Resources, which funds the resource centre, says that GE placed such burdensome terms on the sharing that the NIH eventually gave up. For instance, researchers would not have been allowed to share the results of their research with the NIH, says Portilla.
GE spokesman Conor McKechnie blames the "third parties" from which GE gained the rights to the EGFP protein for the onerous licensing requirements. But David Einhorn, house counsel at the Jackson Laboratory in Bar Harbor, Maine, which distributes mice to researchers around the world, questions GE's contention. He points out that many other mouse models that incorporate the gene for EGFP have been made and shared without objection from GE or from the institutions that originally discovered and licensed the EGFP patents.
Researchers have had trouble sharing resources for decades, but the situation seems to be getting worse. A 2007 study, for instance, found that 18% of academics' requests for research materials from other academic labs were not fulfilled (see 'Limited access') — almost twice as many as found in a survey taken during the 1990s. For materials requested from industry, the 2007 study found, one-third of academics' requests were declined (J. P. Walsh, W. M. Cohen and C. Cho Res. Pol. 36, 1184–1203; 2007).
Companies that don't want to share their resources don't usually publish papers describing them, says lawyer Tania Bubela of the University of Alberta School of Public Health in Edmonton, Canada. A publication changes the picture, she says. "The obligation of publication is to make your data and reagents available, so that people can replicate the results."
With no sign of a resolution, other labs have resorted to remaking the mouse model. Adrian Bird, director of the University of Edinburgh's Wellcome Trust Centre for Cell Biology, UK, says that his lab has re-engineered the mice and will distribute them through a repository, such as the Jackson Laboratory, as soon as his colony is large enough.
Bird and others say that it is unfortunate that scientists have had to delay research on the syndrome and spend money to regenerate a model that could already be in use.
"If you were to ask the families of people affected by this disease, they would say that every minute counts," says Bird.
Source: Nature News
Note: To see the original page click on the title of the post
Stashed away somewhere in a freezer in Cambridge, Massachusetts, is a mouse embryo that Etienne Joly would dearly like to get his hands on.
Joly is an immunologist based in Toulouse, France, with a keen interest in Rett syndrome, an incurable and debilitating disease that almost exclusively affects young girls. The mouse, developed by a team at the Novartis Institutes for Biomedical Research in Cambridge, carries a fluorescently tagged version of the gene that is mutated in the disease. It is the perfect tool, Joly says, for testing an idea he has about Rett syndrome. But a thicket of legal restrictions puts the mouse off-limits to anyone outside Novartis, even though scientists at the company are no longer using the model in their work on Rett syndrome.
"All scientists and families are asking for is the right to look into this disease and to try to understand it better," says Joly, who has embarked on a letter-writing campaign against the restrictions. "And when you know that there is a tool, but you can't use it because some lawyer says that you can't have the materials, then you get angry." Scientists and experts in intellectual-property issues say that the case shows how science can be impeded when onerous licensing rules govern the sharing of research materials.
Girls with Rett syndrome are healthy as babies, then progressively lose the ability to speak, move, eat and breathe normally. Because the disease is rare, affecting just one in 10,000 to 20,000 girls, it is an unattractive target for drug companies. Academic researchers have picked up the slack, and the field has moved at breakneck speed in recent years, from the 1999 discovery that defects in the gene MECP2 cause the disease, to clinical trials of possible treatments today.
Yet no one knows how the mutation causes the disease. A few years ago, Joly, who works at the Institute of Pharmacology and Structural Biology, came up with what he calls a "slightly unconventional" idea that the Rett-syndrome gene might have a role in regulating immune responses in the central nervous system. To explore his hypothesis, Joly needed an animal model that would allow him to trace where the gene is expressed.
In 2008, Joly learned about the engineered mouse. Led by molecular biologist Cecile Blaustein, the Novartis team had joined a copy of the mouse Mecp2 gene to a copy of the gene that makes enhanced green fluorescent protein (EGFP) to produce an animal in which the gene's activity can be traced throughout the brain and body (R. S. Schmid et al. Neuroreport 19, 393–398; 2008).
But after three years of trying, neither Joly nor any other Rett-syndrome researcher has been able to gain access to the mouse. When researchers asked to share it, Blaustein and her colleagues said that they would have liked to but couldn't because of the terms of Novartis's licence on EGFP, which it obtained from GE Healthcare.
Novartis and GE have been unable to negotiate a way to share the mice, says Jeff Lockwood, spokesman for the Novartis Institutes for Biomedical Research — even though Novartis has ended its research project on the mice.
When Monica Coenraads, executive director of the Rett Syndrome Research Trust in Trumbull, Connecticut, tried to broker an agreement to share the mice, GE and Novartis asked the US National Institutes of Health (NIH) in Bethesda, Maryland, to distribute the mice through its Mutant Mouse Regional Resource Centers. But Lili Portilla, senior adviser for technology transfer at the NIH National Center for Research Resources, which funds the resource centre, says that GE placed such burdensome terms on the sharing that the NIH eventually gave up. For instance, researchers would not have been allowed to share the results of their research with the NIH, says Portilla.
GE spokesman Conor McKechnie blames the "third parties" from which GE gained the rights to the EGFP protein for the onerous licensing requirements. But David Einhorn, house counsel at the Jackson Laboratory in Bar Harbor, Maine, which distributes mice to researchers around the world, questions GE's contention. He points out that many other mouse models that incorporate the gene for EGFP have been made and shared without objection from GE or from the institutions that originally discovered and licensed the EGFP patents.
Researchers have had trouble sharing resources for decades, but the situation seems to be getting worse. A 2007 study, for instance, found that 18% of academics' requests for research materials from other academic labs were not fulfilled (see 'Limited access') — almost twice as many as found in a survey taken during the 1990s. For materials requested from industry, the 2007 study found, one-third of academics' requests were declined (J. P. Walsh, W. M. Cohen and C. Cho Res. Pol. 36, 1184–1203; 2007).
Companies that don't want to share their resources don't usually publish papers describing them, says lawyer Tania Bubela of the University of Alberta School of Public Health in Edmonton, Canada. A publication changes the picture, she says. "The obligation of publication is to make your data and reagents available, so that people can replicate the results."
With no sign of a resolution, other labs have resorted to remaking the mouse model. Adrian Bird, director of the University of Edinburgh's Wellcome Trust Centre for Cell Biology, UK, says that his lab has re-engineered the mice and will distribute them through a repository, such as the Jackson Laboratory, as soon as his colony is large enough.
Bird and others say that it is unfortunate that scientists have had to delay research on the syndrome and spend money to regenerate a model that could already be in use.
"If you were to ask the families of people affected by this disease, they would say that every minute counts," says Bird.
Source: Nature News
Note: To see the original page click on the title of the post
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