Monday, December 6, 2010

New Clinical Trial: Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)


The investigators are recruiting children for a research study using a medication known as IGF-1 (mecasermin or INCRELEX) to see if it improves the health of children with Rett syndrome (RTT). To participate in the study your child must be female, between the ages of 2 to 12 and have a genetic diagnosis (MECP2 deletion or mutation) of Rett Syndrome. As you may know, there is no treatment for this illness. Currently, the standard management of Rett syndrome is supportive, which means attempting to prevent complications and treatment of symptoms.

This study involves testing an investigational drug, which means that even though IGF-1 is approved by the Food and Drug Administration (FDA) for use in children, it has not been used before to treat Rett syndrome specifically. Information from this research will help determine whether the drug should be approved by the FDA in the future for the treatment of Rett Syndrome.

There are three goals to this study:

1. As one of the features of Rett Syndrome is unstable vital signs, the investigators are trying to determine if IGF-1 has any effect on normalizing your child's pulse, blood pressure and breathing pattern. During PHASE 2, a device called BioRadio® will be used to monitor vital signs in a non-invasive way. This information will be recorded and stored on the accompanying laptop. Before starting PHASE 2, the investigators would like to "beta-test" the BioRadio® in PHASE 1. As such, the investigators may ask you to try using the BioRadio® with your child to test the fit and the performance of the equipment. Should you choose to enroll your child in PHASE 2, the investigators will then ask that your child wear the BioRadio® for two hours, on two consecutive days every four weeks.
2. The safety of IGF-1 in children with Rett syndrome. The study personnel will ask you to complete a medication diary and side effect reporting form on a regular basis. They will assist you in completing this by telephone interviews. Your child will undergo 2 lumbar punctures performed at the bedside in the clinical research facility. In addition, laboratory tests will be performed throughout the study to evaluate the safety of IGF-1. These will be blood tests similar to those provided in routine clinical care. Your child will undergo regular non-invasive comprehensive physical examinations including neurological and eye examination, tonsil evaluation, electrocardiograms (ECG), measurement of height, weight and head circumference.
3. IGF-1 may improve your child's behavior, communication and speech. In order to measure this, the investigators will evaluate your child once during each month of treatment with neurodevelopmental assessments and a neurological exam. All of the tests used during these evaluations are non-invasive. the investigators will also ask you what your impressions are about her behavior and day-to-day activities through a structured parental interview and various questionnaires.

To read more about this, please click on the title


Saturday, December 4, 2010

Rett Syndrome Documentary on CNN-IBN

Rett syndrome story (Indian Rett syndrome foundation)

Please watch CNN-IBN Channel today (4th December) at 9.30 PM and tomorrow (5th December) at 5.30PM and 10.30PM

Share this information with other too.

Tuesday, November 16, 2010

New Data Uncover Common Molecular Pathways Between Rett Syndrome, Autism and Schizophrenia

The laboratory of Huda Zoghbi, where the discovery that mutations in the gene MECP2 cause the severe childhood neurological disorder Rett Syndrome was made, has taken yet another step toward unraveling the complex epigenetic functions of this gene, implicated also in cases of autism, bipolar disease and childhood onset schizophrenia. The November 11 issue of Nature reports that removing MECP2 from a small group of neurons that typically make the inhibitory neurotransmitter, GABA, recapitulates many symptoms of Rett as well as numerous neuropsychiatric disorders.

The identification of the genetic basis of Rett allowed the development of a number of mouse models of the disorder, accurately reproducing the range of symptoms seen in humans. These are considered to be among the best existing models of neurological disease.

While removing MECP2 from every cell results in full-blown Rett symptoms, the Zoghbi lab during the past few years has been using genetic tools to knock out the gene from distinct subsets of specialized brain cells called neurons, in an attempt to correlate certain neuronal populations with specific symptoms.

GABA (gamma amino butyric acid) is the main inhibitory neurotransmitter in the brain. Neurons releasing GABA regulate the nervous system by acting like traffic lights on the brain’s information highway. Zoghbi and Hsiao-Tuan Chao, a postdoctoral fellow in the lab and lead author of the study, use this analogy to describe the action of GABA in allowing for a balanced level of neuronal activity by controlling the strength and timing of information transfer. Surprisingly, Zoghbi, Chao and colleagues found that removing MeCP2 from the small number of GABA-producing neurons reduced production of the neurotransmitter by about 30%. This reduction reproduced many symptoms of Rett including the paw-clasping that mimics the classical hand-wringing stereotypies. After a brief period of apparently normal development, the mice display brain hyperexcitability, impaired respiration, and loss of muscle control and strength and premature lethality. Learning, memory and sensory responses are also altered. Interestingly, the mice engaged in repetitive movements reminiscent of compulsive behavior seen in a number of neuropsychiatric disorders.

The study raises a number of important points. It implicates GABA as a key player in Rett and suggests that boosting the activity of GABA -producing neurons may help to alleviate the severity of some symptoms. It also begs the question: If a 30% reduction in GABA causes Rett symptoms, could a more subtle perturbation of 10% or 20% lead to certain neuropsychiatric disorders? This study suggests a possible pathway which can now be explored to answer the question fully.

“This study revealed to us the critical role of MECP2 in modulating the levels of GABA in inhibitory neurons and pinpointed all the neuropsychiatric symptoms that develop when the function of inhibitory neurons is compromised. Identifying the cellular and chemical basis of such symptoms is a first step in efforts aimed at understanding and, one day, treating such disorders,” said Zoghbi.

Dr. Zoghbi, who was first drawn into Rett research through her clinical experience at Baylor College of Medicine, is a Howard Hughes investigator and a Rett Syndrome Research Trust Scientific Advisor.

Monica Coenraads, Executive Director at the Rett Syndrome Research Trust which helped to fund this work, says “The field of Rett research has benefited incalculably from Huda Zoghbi’s dedication and perseverance. Her latest results suggest that GABAergic pathways are ripe for exploration not only as therapeutic intervention for Rett Syndrome but also for a much wider class of neurological disease.”

About Rett Syndrome
Rett Syndrome strikes little girls almost exclusively, with first symptoms usually appearing before the age of 18 months. These children lose speech, motor control and functional hand use, and many suffer from seizures, orthopedic and severe digestive problems, breathing and other autonomic impairments. Although some victims of Rett Syndrome do not survive childhood, most live to become adults who require total, round-the-clock care.

About Rett Syndrome Research Trust
The Rett Syndrome Research Trust is the premier organization devoted exclusively to promoting international research on Rett Syndrome and related MECP2 disorders. The goal is clear: to heal children and adults who will otherwise suffer from this disorder for the rest of their lives. With experience and tight focus, RSRT has an unparalleled knowledge base and extensive networking abilities in the world of high level research. RSRT is in a unique position to stimulate, evaluate, support and monitor ambitious and novel scientific projects.

About Baylor College of Medicine
Baylor College of Medicine in Houston is recognized as a premier academic health science center and is known for excellence in education, research and patient care. It is the only private medical school in the greater southwest and is ranked as one of the top 25 medical schools for research in U.S. News & World Report. BCM is listed 13th among all U.S. medical schools for National Institutes of Health funding, and No. 2 in the nation in federal funding for research and development in the biological sciences at universities and colleges by the National Science Foundation. Located in the Texas Medical Center, BCM has affiliations with eight teaching hospitals, each known for medical excellence. Currently, BCM trains more than 3,000 medical, graduate, nurse anesthesia, and physician assistant students, as well as residents and post-doctoral fellows. BCM is also home to the Baylor Clinic, an adult clinical practice that includes advanced technologies for faster, more accurate diagnosis and treatment, access to the latest clinical trials and discoveries, and groundbreaking healthcare based on proven research.

Source: Rett Syndrome Research Trust

Contact Person:
Monica Coenraads
Executive Director, RSRT

PTC Therapeutics: Development of treatment for Genetic Disorder

PTC applies its expertise in RNA biology and drug development to pioneer novel oral treatments for patients living with serious and life-threatening conditions.

Ataluren for Genetic Disorders

Ataluren (PTC124®) is an investigational drug designed to enable the formation of a functioning protein in patients with genetic disorders due to a nonsense mutation.

A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. Ataluren is currently being investigated for use in patients with nonsense mutation cystic fibrosis (nmCF), nonsense mutation hemophilia A & B (nmHA/B) and nonsense mutation methylmalonic acidemia (nmMMA) .

Click here to read Frequently Asked Questions about ataluren.

Translation of an mRNA into protein

Mechanism of Action
In healthy individuals, ribosomes translate the informational code in the mRNA into protein until arriving at a normal stop signal in the mRNA, at which point the ribosome appropriately stops translation and a functioning protein results.

Nonsense mutations, however, create a premature stop signal in the mRNA. This premature stop signal causes the ribosome to halt translation before a functioning protein is generated, creating a shortened, nonfunctioning protein. The resulting disease is determined by which protein cannot be expressed in its entirety and is no longer functional (eg, the CFTR protein in nmCF. the Factor VIII/Factor IX protein in nmHA/B or the dystrophin protein in nmDBMD ).

Ataluren is designed to allow the ribosome to ignore the premature stop signal and continue translation of the mRNA, resulting in formation of a functioning protein. Ataluren does not cause the ribosomes to read through the normal stop signal.

Ataluren, taken orally, has the potential to address the underlying cause of the disease by overriding the premature stop signal, enabling the synthesis of a functioning protein. Ataluren does not alter the patient’s genetic code or introduce genetic materials into the body.

Nonsense Mutation Genetic Disorders
The National Institutes of Health (NIH) Office of Rare Diseases estimated that rare diseases affect 25 million people in the US and that the majority of these people have genetic disorders. In more than 2,400 genetic disorders, a nonsense mutation causes the disease in an average of 5 to 15% of the patients. Besides nonsense mutation Duchenne/Becker muscular dystrophy (nmDBMD), nonsense mutation cystic fibrosis (nmCF), nonsense mutation hemophilia A & B (nmHA/B) and nonsense mutation methylmalonic acidemia (nmMMA), these genetic disorders include a range of serious diseases across multiple therapeutic areas including, spinal muscular atrophy, lysosomal storage disorders, and some forms of cancer.

PTC124 Targets Genetic Disorders Caused by Nonsense Mutations

(Click the link above to read the article)

Genetic Testing
Ataluren has the potential to treat any genetic disorder caused by a nonsense mutation. Although current clinical trials involve only nonsense mutation CF and nonsense mutation HA/B, future trials are anticipated in other genetic disorders caused by a nonsense mutation. To determine whether a genetic disorder is caused by a nonsense mutation, patients require genetic testing. Genetic testing is done by a simple blood test that is ordered by a physician working in concert with a genetic lab.

Laboratories performing genetic testing vary by disorder and location. The NIH-funded website, provides a listing of laboratories and contact information.

Ongoing Clinical Trials

* nmCF: PTC has initiated a longer-term, Phase 3 clinical study of ataluren in patients with nonsense mutation CF. The main goals of this study are to understand whether ataluren can improve how nmCF patients feel and function and whether the drug can safely be given over a long period. The trial is a multi-center, randomized, double-blind, placebo-controlled study.
* nmHA/B: PTC has initiated a Phase 2a clinical trial of ataluren in patients with nonsense mutation hemophilia type A and B (nmHA and nmHB). The trial is a multi-center, open label, dose escalation study. The main goals of the trial are to determine whether treatment with ataluren can result in an increase in Factor VIII or IX levels and whether the drug can safely be given to people with severe hemophilia due to a nonsense mutation.
* nmMMA: PTC has initiated a Phase 2 clinical trial of ataluren in patients with nonsense mutation methylmalonic acidemia (nmMMA). The trial is a non-randomized, open-label trial. Its main goals are to understand whether ataluren can be tolerated and can decrease MMacid levels.

Completed Clinical Trials


Phase 2b Data nonsense mutation DBMD (nmDBMD): Final analyses of Phase 2b efficacy data suggest the investigational new drug ataluren slowed the loss of walking ability in patients. The primary endpoint of the Phase 2b trial was the change in 6-minute walk distance (6MWD) from baseline to 48 weeks. The data showed a 29.7 meter (approximately 97 feet) difference in the average change in 6MWD when comparing the ataluren (10-, 10-, 20-mg/kg) and placebo arms. This result is consistent with the study hypothesis of a 30-meter difference and the average change in 6MWD observed in registration-directed trials of approved drugs for other diseases.

* Phase 2a Data nonsense mutation DBMD (nmDBMD): Data from Phase 2a clinical trials of ataluren in pediatric patients with nmDBMD show that administration of ataluren is associated with production of functional dystrophin. Ataluren treatment has also been associated with statistically significant reductions in the leakage of muscle-derived creatine kinase into the blood.
* Phase 2a Data nonsense mutation CF (nmCF): Data from Phase 2a clinical trials of ataluren in pediatric and adult patients with nmCF show that administration of ataluren results in production of functional CFTR and statistically significant improvements in CFTR chloride channel function in the airways. Ataluren treatment was associated with reductions in cough frequency and improvements in pulmonary function tests.
* Adverse Events and Safety Profile: Across all clinical studies to date, including Phase 1 healthy-volunteer studies, ataluren has been generally well tolerated. Mean compliance has been >90% in all studies.

The development of ataluren has also been supported by grants from:

* Cystic Fibrosis Foundation
* Parent Project Muscular Dystrophy
* Muscular Dystrophy Association
* FDA’s Office of Orphan Products Development
National Center for Research Resources
* National Heart, Lung, and Blood Institute

The FDA has granted PTC124® (ataluren) Subpart E designation for expedited development, evaluation, and marketing and has granted Orphan Drug designations for the treatment of CF and DBMD due to nonsense mutations. PTC124® (ataluren) has also been granted orphan drug status for the treatment of CF and DBMD by the European Commission.

Partnership with Genzyme
PTC Therapeutics, Inc. and Genzyme Corporation have an exclusive collaboration to develop and commercialize ataluren. PTC will commercialize ataluren in the United States and Canada and Genzyme will commercialize ataluren in all other countries.

To receive status updates on ataluren, please visit the Contact Us page of the website and join our mailing list.

Patients, families and advocacy groups may also contact Ms. Diane Goetz, Director, Patient and Professional Relations, 866-282-5873 or 908-912-9256 or

Source: PTC Therapeutics

Note: Click the title to read more about PTC therapeutics and its developments.

RETT SYNDROME IN A PETRI DISH: Rett Syndrome Research trust Interview series

On November 11th the high-profile journal Cell published a paper by Alysson Muotri, Ph.D. entitled A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells. The stem cell field has seen amazing progress in the last few years. Induced Pluripotent Stem Cells (iPS cells) is an especially hot area because of the clinical implications. Simply put, iPS cells allow you to study diseased cells up close and personal through their entire lifecycle. Importantly, any deficits that are identified in the cells can be used as read-outs in drug screening endeavors.

Interviewed by Monica Coenraads
(Co-Founder, Trustee, Executive Director of RSRT)

I’ve had the pleasure of knowing Dr. Muotri for a number of years, in fact since his introduction to Rett about six years ago. He became interested in the disorder while doing his post-doc in the lab of Fred (Rusty) Gage at the Salk Institute in La Jolla, CA. Thankfully his interest has continued now that he is an independent investigator at UCSD.

Below is an excerpt from a conversation Dr. Muotri and Monica Coenraads had regarding his paper.

MC Dr. Muotri, congratulations on your Cell paper which has strong implications for drug development and therefore is of interest to anyone who loves a child with Rett Syndrome. I know this is a very hectic time so thank you for taking time out to speak with me.

I’m curious, what drew you to a science career?

AM I’ve always been interested in understanding how things work. I reasoned that science was the most obvious way to achieve that. You know that I’m from Brazil. I received my PhD in genetics from the University of São Paulo. I started off in the cancer biology field but quickly switched to neuroscience in 2002 when I moved to the Salk Institute. I was there for 6 years until I got my current position here at UCSD two years ago.

MC I’m assuming it was a significant switch moving into neuroscience from cancer biology.

AM Yes, it was a bit intimidating in the beginning because there was so much to learn. But I welcomed the challenge. And as it turned out my experiences from cancer were beneficial for my transition into neuroscience. For example, when I moved to Rusty’s lab one of the first observations we made was related to a phenomenon called transposons. I knew from my previous work that retrotransposons are very active in cancer cells and I remember discussing this with my neuroscience colleagues. Most of them were not very familiar with this phenomenon and assumed it was insignificant. My feeling was that if these transpositions were really happening in the brain it would be better to look at it closely because it could be involved in a new mechanism related to brain development.

MC Since retrotransposons are actually the topic of your next Rett paper coming out in Nature soon let me take a moment to give our readers a little background information.

Retrotransposons are sequences of DNA that move around and insert themselves into new positions within the genome. Barbara McClintock received the Nobel Prize in 1983 for her discovery of this phenomenon. Historically retrotransposons have been considered “junk DNA” because they occupy around 50% of the mammalian genome and do not have a clear function in the cell. It’s probably more likely that transposons have a biological function which remains, for the moment, unknown to us. Retrotransposons have been linked to disease.

Dr. Muotri, would you like to give us a glimpse into your upcoming paper that deals with retrotransposons in Rett Syndrome?

AM So the idea is that retrotransposons , which jump around inserting themselves into the genome, result in neurons, in the same individual, which are genetically different from each other. We observed that MECP2, the gene involved in Rett Syndrome, is a major repressor of this activity. Also, we determined that these jumping events are pretty much exclusive to the brain and MECP2 seems to be one of the gate keepers controlling the amount of the activity.

MC So in a brain that is deficient in the MeCP2 protein there would be increased jumping events?

AM That is right. It remains to be seen whether these extra events contribute to the symptoms of Rett or whether the brain simply compensates and manages to work around them. We are working on this question now.

MC Fascinating. I look forward to continuing our dialogue on this subject as your research progresses. Two high profile papers in one month – very impressive.

Now, getting back to iPS. This is a field that has seen amazing advances in a short period of time. Can you highlight for our readers the excitement surrounding these cells?

AM The dream of neuroscientists is to understand the early stages of a neurological disorder. Until recently we had two options to achieve this. One is to develop a mouse model that will hopefully recapitulate the symptoms seen in humans. Of course a limitation of a mouse model is that it’s a mouse and not a human – the brain of a human is so much more complex. The other option is post-mortem brain tissue. The problem is that at that stage the damage is already done and what you see is the end stage of a disease. To really study a disease it’s beneficial to have the most primitive cell line possible and then to coax these cells into a variety of different cell populations and to study what happens at various time points.

An important breakthrough happened a few years ago that has made this type of work very feasible. The Japanese group headed by Shinya Yamanaka surprised the world when they showed that you can reprogram cells that have already differentiated back to a more naïve state resembling a human embryonic stem cell. This allows us to capture the genome of a person, including any genetic mutations, and allows us to study the neurons and other cells of interest and see how a disease progresses and what changes happen at the molecular level.

MC In general the Rett field has relied on the mouse models as their standard assay. In terms of drug screening that’s a very expensive assay. Having iPS lines with MECP2 mutations gives scientists the ability to have a cellular assay to screen for therapeutics. Thousands, and in fact, hundreds of thousands of compounds can be efficiently and quickly screened in cell lines using either low or high throughput technologies.

Can you tell us about the phenotypes that you have identified in the cells. (a phenotype is an observable characteristic or trait)

AM One of the phenotypes was related to cell soma size (cell body) of a neuron. Just looking at neurons under the microscope we saw that Rett neurons are reduced in size by 10%. That might not seem like a big deal but when you consider the 3 dimensional structure of the neuron; a 10% reduction is very significant. So size was the simplest read-out that we found.

Another phenotype is related to the morphology of neurons. (Morphology is the study of the structure and form of an organism.) The idea to look at morphology was inspired by the reports over the last decade from post-mortem brain tissue in both people and animal models. We focused on the number of spine densities in neurons and we also saw a reduction. (A dendritic spine, or simply spine, is a small membranous protrusion from a neuron’s dendrite that typically receives input from a synapse.) We looked at neuronal networks and found deficiencies in their ability to communicate.

MC You made iPS cells with different MECP2 mutations. You found that the phenotypes were consistent among mutations. Can you elaborate?

AM Yes, the four different mutations we studied led to similar phenotypes. At least the phenotypes we looked at. We were convinced that this was a strong suggestion pointing to a loss of MeCP2 function. Thus, we knocked down MeCP2 expression from control neurons and obtained the same result. We then, restored the normal MeCP2 gene in Rett neurons, suppressing the phenotypes. In combination, these experiments suggest that MeCP2 is responsible for the alterations in Rett neurons. The fact that several MeCP2 mutants revealed a similar phenotype has clinical relevancy because it may indicate that a single drug may correct them all.

MC So the goal is to use these cells as a platform for drug screening.

AM Absolutely. As a proof of principle we added a growth factor, IGF1, to the cells. As you know a paper was published in PNAS in early 2009 showing that a compound similar to IGF1 improved some of the symptoms in mice so we decided to try it in our system. We found that IGF1 corrected the phenotype, in fact it over-corrected. The over-correction is something that needs to be considered in terms of the clinical trial, a proper dose tuning in each patient is desirable. Also, something to keep in mind is that while I put IGF1 directly into the cells in the clinical trial the IGF1 has to get into the brain and we know that that doesn’t happen as much as we would like.

The other drug we tried is gentamicin , an antibiotic that has the ability to “read through” premature stop codons (nonsense mutations that end in X, such as 255X, 168X) . We found that gentamicin restored levels of the MeCP2 and phenotypically rescued the cells.

MC That is pretty interesting especially in light of the fact that read through drugs act by substituting the stop codon with a random amino acid. So in effect they swap out one mutation for another.

AM We checked that and found that the protein level was normal but there was no way for us to see what mutation was inserted. Part of the new protein that is synthesized in the presence of gentamicin, is probably correct and we believe that is exactly what is reverting the phenotypes.

MC It’s important to note that gentamicin is highly toxic and doesn’t cross the blood brain barrier very well either so this is not a drug that can be used now for the treatment of Rett Syndrome. There are however other drugs with similar modes of action that being tested in animal models.

But the take home message from your data is that iPS cell lines are an in vitro model system for Rett Syndrome and can be utilized in a drug screening platform. What are next steps to utilize the iPS lines as a platform for drug screening?

AM The next step is to scale this up and that is not easy to do. Because the experiments are very sensitive to variables and there are many steps during the conversion of the iPS cells to neurons. Thus, we need to systematically validate all the variables and make the system as robust as possible. Finally, we need to choose the appropriate read-outs (the cellular phenotypes) we would like to use. It is important to design these experiments carefully so one doesn’t lose time with false positives. My lab was recently awarded a CIRM grant (California Institute for Regenerative Medicine) exactly to optimize these steps, so I would like to start this as soon as possible. Finally, I would like to test libraries of drugs that previously failed clinical trials for other diseases. Drug repositioning, as this concept is called, is attractive because repurposed drugs can bypass much of the early cost and time needed to bring a drug to market.

MC I found your paper very encouraging for a number of reasons. Firstly, your data continues to confirm and validate the concept that Rett is reversible. Secondly, you showed that the iPS platform can be used for drug screening. Thirdly, your data suggests that while there may be many mutations in MECP2, they may share common phenotypes. That may be an important issue in terms of treatment strategies.

Dr. Muotri, I’m sure I speak for every Rett family who reads this interview … we wish you great luck and god speed in your work.

Source: Rett Syndrome Research Trust (RSRT)

Note: Click on the title the full interview and video

Monday, November 15, 2010

Women of the year 2010: Julia Roberts

Julia Roberts: The Class Act

She is a Woman of the Year because: “There are not a lot of people who can do everything she does, and be brilliant, and be gorgeous, and raise all those children. Formidable, my dear. Bravo.”
—Joanne Woodward, actress

November 1, 2010
by Susan Dominus

You have to admire that Julia Roberts arrives at an interview in the kind of standard-issue black pants that mothers rely on when they want to look presentable. Wearing the barest hint of makeup, she’s soon chatting about the challenge of running a house with three kids—six-year-old twins Hazel and Phinnaeus, and three-year-old Henry. “Trust me,” she confides, “some weeks are cleaner than other weeks.”

Not that she’s had much time lately to worry about the housecleaning. Her 2010 has been huge. She’s graced countless magazine covers and TV shows on behalf of her blockbuster Eat, Pray, Love; she produced a documentary on the power of motherhood that will air on Oprah’s OWN network in January; and she filmed her next sure-to-be hit, Larry Crowne, with pal Tom Hanks.

Despite her successes, though, Roberts says, “It’s all about the home.” Turns out one of the world’s biggest female movie stars (collective box office: more than $2 billion) is an eco-sensitive earth mother who composts and drives a tractor at her New Mexico ranch. At 43, the Oscar winner chooses roles that allow her to spend quality time with her family—proof, as she’s said, that “becoming famous doesn’t make you crazy.” Once called the Hillary of Hollywood for her trailblazing—she was the first actress to get more than $20 million for a film—Roberts has used that money and clout for good. Since 1997 she’s supported Paul Newman’s Hole in the Wall Gang camp for children with grave illnesses. She also campaigns to fund research for Rett Syndrome (a neurodevelopmental disorder that can destroy kids’ ability to walk and speak) and serves on the board of Earth Biofuels, which promotes renewable energy.

But it’s Roberts’ unique, lit-from-within quality that’s made her everyone’s favorite screen icon. In the words of Eat, Pray, Love author Elizabeth Gilbert, “The only other job she could have would be professional fairy.” Well, she did once play Tinkerbell.

Source: Glamour

Inhibitory neurons key to understanding neuropsychiatric disorders

HOUSTON -- (Nov. 11, 2010) – The brain works because 100 billion of its special nerve cells called neurons regulate trillions of connections that carry and process information. The behavior of each neuron is precisely determined by the proper function of many genes.

In 1999, Baylor College of Medicine ( researcher Dr. Huda Zoghbi (, and her colleagues identified mutations in one of these genes called MECP2 as the culprit in a devastating neurological disorder called Rett syndrome ( In new research in mice published in the current issue of the journal Nature (, Zoghbi and her colleagues demonstrate that the loss of the protein MeCP2 in a special group of inhibitory nerve cells in the brain reproduces nearly all Rett syndrome features.

Children, mostly girls, born with Rett syndrome, appear normal at first, but stop or slow intellectual and motor development between three months and three years of age, losing speech, developing learning and gait problems. Some of their symptoms resemble those of autism.

These inhibitory (gamma-amino-butyric-acid [GABA]-ergic) neurons make up only 15 to 20 percent of the total number of neurons in the brain. Loss of MeCP2 causes a 30 to 40 percent reduction in the amount of GABA, the specific signaling chemical made by these neurons. This loss impairs how these neurons communicate with other neurons in the brain. These inhibitory neurons keep the brakes on the communication system, enabling proper transfer of information.

"In effect, the lack of MeCP2 impairs the GABAergic neurons that are key regulators governing the transfer of information in the brain", said Dr. Hsiao-Tuan Chao (, an M.D./Ph.D student in Zoghbi's laboratory and first author of the report.

Chao made the discovery by developing a powerful new tool or mouse model that allowed researchers to remove MeCP2 from only the GABAergic neurons.

"We did this study thinking that perhaps all we would see was a few symptoms of Rett syndrome," said Chao. "Strikingly, we saw that removing MeCP2 solely from GABAergic neurons reproduced almost all the features of Rett syndrome, including cognitive deficits, breathing difficulties, compulsive behavior, and repetitive stereotyped movements. The study tells us that MeCP2 is a key protein for the function of these neurons."

Once the authors determined that the key problem rested with the GABAergic neurons, they sought to find out how the lack of MeCP2 disturbed the function of these neurons. Chao discovered that losing MeCP2 caused the GABAergic neurons to release less of the neurotransmitter, GABA. This occurs because losing MeCP2 reduces the amount of the enzymes required for the production of GABA.

Intriguingly, prior studies showed that expression of these enzymes is also reduced in some patients with autism, schizophrenia and bipolar disorder, said Chao.

"This tells us a lot about what is going on in the brains of people with Rett syndrome, autism or even schizophrenia," said Chao. "A child is born healthy. She starts to grow and then begins to lose developmental milestones. Communication between neurons is impaired, in part due to reduced signals from GABAergic neurons."

"This study taught us that an alteration in the signal from GABAergic neurons is sufficient to produce features of autism and other neuropsychiatric disorders," said Zoghbi, a Howard Hughes Medical Institute investigator and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.


Others who took part in this work include Hongmei Chen, Rodney C. Samaco, Mingshan Xue, Maria Chahrour, Jong Yoo, Jeffrey L. Neul, Hui-Chen Lu, Jeffrey L. Noebels and Christian Rosenmund, all of BCM, John L.R. Rubenstein of University of Calfornia in San Francisco, Marc Ekker of University of Ottawa in Ontario, and Shiaoching Gong and Nathaniel Heintz of The Rockefeller University in New York.

Funding for this work came from the Howard Hughes Medical Institute, the National Institute of Neurological Disorders and Stroke, the Simons Foundation, the Rett Syndrome Research Trust, the Intellectual and Developmental Disability Research Centers, the International Rett Syndrome Foundation, Autism Speaks, the National Institute of Mental Health, Baylor Research Advocates for Student Scientists and McNair Fellowships.

When the embargo lifts, this report will be available at

For more information on basic science research at Baylor College of Medicine, please go to

Source: EurekaAlert

Thursday, November 11, 2010

Website of Indian Rett Syndrome Foundation

The Website of Indian Rett syndrome Foundation was launched by Major General Ian Cardozo, Chairman of Rehabilitation Council of India and Mrs. Poonam Natrajan, Chairperson, National Trust of India in the 3rd Annual Rett Syndrome Awareness meeting, which was organized by Indian Rett Syndrome foundation and was hosted by Department of Pediatrics, AIIMS, New Delhi on 31st October, 2010.

Please click on the link or copy and paste the following link to visit the website of "Indian Rett Syndrome Foundation". You can also click on the title above to visit the site.

Indian Rett Syndrome Foundation

Wednesday, October 6, 2010

Life threatening breathing disorder of Rett syndrome prevented

October 2010

A group of researchers at the University of Bristol have sequestered the potentially fatal breath holding episodes associated with the autistic-spectrum disorder Rett syndrome.
Rett syndrome is a developmental disorder of the brain that affects around 1 in10,000 young girls. One of the worse clinical disorders is the intermittent episodes of breath holding, putting the patient at risk of asphyxiation and further brain damage. Other disorders include repetitive hand movements, digestive and bowel problems, seizures, learning disability with lack of verbal skills and social withdrawal, making it a thoroughly debilitating disease.

However, an international team of researchers based at Bristol’s School of Physiology & Pharmacology have discovered a way to prevent these episodes of breath holding in a mouse model of Rett syndrome. Using a unique combination of drugs, they have discovered that the area of the brain that allows breathing to persist throughout life without interruption has reduced levels of a transmitter substance called aminobutyric acid.

Professor Julian Paton, who co-led the research, said: “These findings make a significant step in our understanding of the reasons why breathing is intermittent in Rett syndrome and give exciting hope for the future for alleviating young girls from these awful life threatening episodes of breath holding, which they experience regularly throughout the day.”

This autistic condition is caused by a spontaneous mutation in the gene that encodes for methyl-CpG-binding protein 2 or MeCP2. MeCP2 is very abundant in the brain and is a transcription factor that decodes DNA essential for making proteins in brain cells.

The researchers found that by increasing both the amount of aminobutyric acid (a vital brain signalling substance) and stimulating a specific type of serotonin receptor within the brain to suppress the activity of brain cells that normally depress inhalation, this abolished the life threatening episodes of breathing arrests.

“These exciting findings are particularly relevant since the drugs we used already have approval for use in humans to treat other illnesses, so the hope is that our findings can soon be translated across to sufferers of Rett Syndrome, and possibly other breathing disorders” said Professor John Bissonnette from the Oregon Health and Science University in Portland who co-led the study.

The findings of the study, which was funded by the International Rett Syndrome Foundation and the National Institutes of Health, are revealed in a paper published by the journal – Proceedings in the National Academy of Science (PNAS).

Note: Click on the title to read the original News

Source: Bristol University News

Sunday, October 3, 2010

Third Annual Rett syndrome Awareness Meeting

The month of October is celebrated as "Rett syndrome Awareness Month" all around the world. We are going to organize our third Annual Rett Awareness Meet.

Date and Time
Sunday, October 31 · 10:00am - 5:00pm

Teaching Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, INDIA

Come and Join us to Raise More Awareness about Rett syndrome, a neurodevelopmental disorder. which primarily affects girls.

If you have any queries, please contact us at



Indian Rett Syndrome Foundation & Genetics Unit, Dept. of Pediatrics, AIIMS

New Delhi, INDIA


Monday, September 13, 2010

From eugenic euthanasia to habilitation of "disabled'' children- Andreas Rett's contribution

By Ronen GM and colleagues

Note: Click on the title to read and download the full article

Source: Google Docs

Genome-wide, yet narrow

By Petrus J de Vries

Note: Click on the title to read and download the full article

Source: Google Docs

Endocrinological study on growth retardation in Rett syndrome

Interesting Article by

Dr. Huppke and Colleagues

Source: Google Docs

Can Children with Autism Recover? If So, How?

Interesting article by

Molly Helt and colleagues

Source: Google Docs

Sudden Death and Cardiac Arrhythmias in Rett Syndrome

Source: Google Docs

X Chromosome Inactivation and Autoimmunity

Interesting article by Dr. Brooks

Source: Google docs

Diagnostic Criteria for Zappella variant of Rett syndrome (the preserved speech variant)

Interesting Article by

Dr. Renieri and colleagues

Souce: Google Docs

Insulin-Like Growth Factor-I Stimulates Histone H3 and H4 Acetylation in the Brain in Vivo

Source: Google docs

Genetics and neuropsychiatric disorders: Treatment during adulthood

A very Interesting article by

Dan Ehninger & Alcino J Silva

Source: Google Docs

BDNF Gene Val66met Polymorphism Associated Grey Matter Changes in Human Brain

Very Interesting Article by

Eker et al

Source: Google Docs

Tuesday, September 7, 2010

Rett Syndrome Documentry Promo Video

The story behind Rett Syndrome is complicated. It involves a devastating genetic affliction that starts with young girls and includes incredible family dynamics, groundbreaking treatment, care and science. The film will focus on Rett families and the optimism surrounding treatments and forward thinking scientific breakthroughs.

Source: REM Entertainment Channel

Monday, August 16, 2010

MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212

Very recent and interesting article by team of "The Scripps Research Institute–Scripps Florida"

Heh-In Im, Jonathan A Hollander, Purva Bali & Paul J Kenny

Source: Nature Neuroscience

Note: Click on the title to read full article

MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants

Very interesting study by Deng et al., 2010

Source: Nature neuroscience

Note: click on the title to read full article

Friday, August 13, 2010

MECP2 Duplication syndrome


Cocaine Addiction Linked to Protein That Causes Rett Syndrome

Drug Discovery & Development - August 11, 2010

Scientists from the Florida campus of The Scripps Research Institute have identified a protein that may act as the trigger controlling the addictive impact of cocaine in the brain. The findings may one day lead to new therapies to treat addiction.

The study was published on August 15, 2010, in the journal Nature Neuroscience.

The results from the new study strongly suggest that a protein known as methyl CpG binding protein 2 (MeCP2) interacts with a type of genetic material known as microRNA to control an individual’s motivation to consume cocaine.

“The study shows that MeCP2 blunts the amount by which microRNA-212 is increased in response to cocaine,” said Paul Kenny, an associate professor in the Department of Molecular Therapeutics at Scripps Florida who led the study. “We have previously shown that miR-212 is very protective against cocaine addiction. Therefore, the conclusion is that MeCP2 may regulate vulnerability to addiction in some people through its inhibitory influence on miR-212. Without this influence, the expression of miiR-212 would be far greater in response to cocaine use, and the risk of addiction would likely be far lower.”

This is the first time that MeCP2 has been shown to play a role in regulating cocaine addiction. Previously, the protein was most linked to Rett syndrome, a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females.

Interactions Shape Vulnerability
These new findings come on the heels of another cocaine addiction study by Kenny and his Scripps Florida colleagues published in the journal Nature in early July. That study showed for the first time that miR-212 — a type of small non-protein coding RNA that can regulate the expression levels of hundreds or even thousands of genes —influenced response to the drug in rats. Animals with increased miR-212 expression were less motivated to consume cocaine, pointing to the protective effects of miR-212 against cocaine addiction.

“The new findings are a significant advance from this previous study,” Kenny said, “because they clearly demonstrate why microRNA-212 is not always fully protective – because MeCP2 regulates by how much miR-212 levels will increase in response to cocaine. This suggests that our initial findings may be central to explaining the complex process of addiction, and understanding how miR-212 signaling is regulated will be important. This study adds another level of detail to the blueprint.”

A major goal of drug abuse research is to understand why certain individuals make the switch from casual to compulsive drug use and develop into addicts. Periods of easy access to the drug, along with repeated overconsumption, can quickly trigger the emergence of addiction-like abnormalities in animal models.

In the new study, the scientists first looked at the expression of MeCP2 in the brain after exposure to cocaine. They found that expression was increased in those animals given extended access to the drug.

“At that point,” Kenny said, “we wanted to know if this increase was behaviorally significant – did it influence the motivation to take the drug?"

Using a virus to disrupt expression of MeCP2, the scientists found that rats consumed less and less cocaine. Intriguingly, levels of miR-212 were also far higher in those animals. Because increases in miR-212 suppress attraction to cocaine, the disruption of MeCP2, in essence, put miR-212 in charge and reduced vulnerability to the drug.

“We concluded that MeCP2 may play an important role in addiction by regulating the magnitude by which miR-212 expression is increased in response to cocaine," said Kenny. "In other words, MeCP2 seems to control just how much you can protect yourself against the addictive properties of cocaine."

Intriguingly, that was not the end of the story. In addition to MeCP2 blunting miR-212 expression, the scientists also found that the opposite was also true – that miR-212 could in turn decrease levels of MeCP2. This suggests that both are locked together in a regulatory loop. Importantly, the two had opposite effects on the expression of a particular growth factor in the brain – called BDNF – that regulates just how rewarding cocaine is.

While the new study fills in an important piece of the puzzle, the Kenny lab is hard at work to further increase our understanding of addiction.

“We still don’t know what exactly influences the activity levels of MeCP2 on miR-212 expression,” Kenny said. “Now we plan to explore what drives it – whether it’s environmentally driven, and if genetic and epigenetic influences are important.”

Source: The Scripps Research Institute

Wednesday, August 11, 2010

Yet Another Door Opens: Neuroimmunology: Rett Syndrome Research Trust Interview Series

Considering Microglia, T Cells and Bone Marrow Transplants in Rett Syndrome

Today we interview Jonathan Kipnis, PhD, a neuroimmunologist who is looking at how the immune system interacts with the nervous system in Rett Syndrome, and is experimenting with ways to engage that interaction to impact Rett symptoms. The immune system is complex and multifaceted, with inflammatory and anti-inflammatory actions and modulatory influences on various other substances, including neurotrophic factors such as BDNF, familiar to parents who follow Rett research. RSRT is supporting his innovative exploration of bone marrow transplants in Rett models.

To read full Interview, please click on the title

Source: Rett Syndrome Research Trust

Wimbledon finalist Vera Zvonareva has embraced fight vs. Rett Syndrome

Tuesday, August 3, 2010

Father’s mission to find a cure for his girl

A DAD has helped set up a charity for his disabled daughter, who suffers from a rare genetic condition.

Andy Stevenson, aged 41, of Pinewood Road, Burtonwood, registered the Rett Syndrome Research Trust (RSRT) UK for 10-year-old Beth, who suffers from the neurological disease, which causes severe physical and learning difficulties.

‘A cure for Rett syndrome is possible in the near future. I am keen to do all I can to help that happen ...'
Andy Stevenson

Rett syndrome, which has no cure, is an autism spectrum disorder that can develop in otherwise healthy young girls, just as they are beginning to speak and walk, robbing them of these emerging skills.

Beth needs 24-hour care, spends most of her time in a wheelchair, is unable to speak and suffers from epilepsy.

Andy, a golf pro at Mersey Valley Golf and Country Club who is married to Lisa, aged 42, said: “All the trustees are very excited that we are up and running. A cure for Rett syndrome is possible in the near future.

“I am keen to do all I can to help that happen for Beth and future generations.”

Andy founded the charity with five other families affected by Rett syndrome and he hopes their efforts will lead to improved treatments to ensure it becomes the first ever reversible brain disorder.

To help achieve this RSRT UK will work closely with a US partner of the same name.

The organisation’s first event, a gala reception, is planned for November 18, and will be held in London with guest of honour Professor Adrian Bird of the University of Edinburgh, who is a scientific advisor to the trust.

Rachael Bloom, chairman of the board of trustees who has a 14-year-old daughter who suffers with the disorder, said: “RSRT UK formed when a group of families came together with the belief that parents must take an active role in the fight against Rett syndrome.

“We want to see this research driven to its conclusion, replicating the results of the reversal experiments not in mice, but in girls and women living with Rett syndrome today.”

When Beth was diagnosed in 2002, Andy’s fundraising challange saw him take part in the Leeds and Loch Ness marathons. He also completed a gruelling assault course called Tough Guy, which took place in Wolverhampton in January and involved running through fire and crawling under barbed wire.

For more information visit

Source:# This Is Cheshire » News

Thursday, July 29, 2010

New Epigenetic Player Implicated in Mental Retardation and Facial Birth Defects

The study, published online July 11 in the journal Nature, reveals that this enzyme is a histone demethylase and works with a key genetic partner to help keep neuronal cells alive during development of the embryonic brain. Patients with this form of mental retardation are known to have mutations in the gene that encodes the active part of this enzyme. The findings may help scientists further understand the underlying biological reasons why X-linked disorders cause cognitive impairment and develop new therapies to treat or prevent them.

"Human genetics has made great strides in identifying genes as potential causes of diseases and disorders, but we don't know much about how they work," says senior author Yang Shi, PhD, the Merton Bernfield Professor of Neonatology in the Newborn Medicine division at Children's. "We knew this was a biologically relevant gene. We wanted to understand the etiology, so we asked why the gene causes problems when it is mutated. Here, we have identified a direct target in neuronal and craniofacial development."

The fast-moving young field known as epigenetics is revealing the dynamic structures and processes that organize, index and control access to the information stored in the DNA code. The epigenetic program orchestrates different combinations of gene activity -- allowing cells with identical genomes to be transformed into more than 200 different specialized tissues and organs in our bodies.

When most people think of DNA, they picture the iconic spiraling ladder of naked DNA. But in nature, the twisting double-helix strands actually spool around clusters of proteins called histones with protruding "tails" that act like specialized antennas, transmitting directions for DNA. This dynamic structure, called chromatin, extends the genetic code by offering, measuring or limiting access to different genes.

Several years ago, Shi and his colleagues identified the first enzyme that can detach a molecule known as a methyl group, previously thought to be a permanent fixture, from the histones tails. Then his team and a number of other research groups independently discovered members of a second known family of these enzymes, known collectively as histone demethylases.

The latest study began with a gene mutated in several male patients with X-linked mental retardation and craniofacial abnormalities. The gene codes for an enzyme that looked a lot like a member of the second family of histone demethylases. The mutations in these patients abolished the working part of the enzyme that plucks the methyl group from the histone tail.

Led by Hank Qi, PhD, co-first author and postdoctoral fellow, the researchers demonstrated in human cells that the enzyme, PHF8, indeed works as a histone demethylase. (And it is the first known demethylase discovered for a strategic methylation point on the tail of histone 4 known as H4K20, which other evidence suggests plays a critical role in gene expression and regulation and in the DNA damage response.) In this case, by removing the methyl group, the enzyme appears to maintain active gene transcription.

"The histone methylation and demethylation doesn't turn the gene on or off," Qi says. "When this histone mark changes, it generates an equilibrium important for fine-tuning gene expression."

Despite its widespread presence, the enzyme seems to have a narrowly targeted biological effect on a master genetic regulator of craniofacial development, the transcription factor MSX1. Taking a cue from the scientific literature, Qi and his collaborators, Madathia Sarkissian and Thomas Roberts at Dana-Farber Cancer Institute, tested the normal enzyme function in zebrafish, a popular model for genetic function.

It is hard to judge cognitive impairment in a small fish, but the dramatic impact on craniofacial development was obvious. Fish without the enzyme developed virtually no jawbone, a condition that could be prevented by providing the functioning enzyme, showing its importance in development. As importantly, providing more of the fish version of the MSX1 gene (whose activity the demethylase enzyme encourages) also partially prevented the biological defects caused by the missing enzyme.

Hope for the reversibility of some aspects of mental retardation arose three years ago in a Scottish mouse study of Rett syndrome, a disorder on the autism spectrum that is also a cause of severe mental retardation in girls. The disease is caused by a molecule, MeCP2, that binds to methylated DNA and may be involved in another form of epigenetic regulation.

"In practical terms, we use gene expression as a read out," says Shi, also a professor of pathology at Harvard Medical School. "Epigenetic states affect the expression of critical genes. These studies suggest that the imbalance of histone methylation dynamics plays a critical role in mental retardation. You can imagine a therapeutic approach to enhance the compromised enzymatic activity or to restore the downstream function."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Children's Hospital Boston.

Journal Reference:

1. Hank H. Qi, Madathia Sarkissian, Gang-Qing Hu, Zhibin Wang, Arindam Bhattacharjee, D. Benjamin Gordon, Michelle Gonzales, Fei Lan, Pat P. Ongusaha, Maite Huarte, Nasser K. Yaghi, Huijun Lim, Benjamin A. Garcia, Leonardo Brizuela, Keji Zhao, Thomas M. Roberts & Yang Shi. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature, 2010; DOI: 10.1038/nature09261

source: ScienceDaily

Tuesday, July 27, 2010

Friday, July 23, 2010

Vote to 'refresh' research on Rett Syndrome

Although Rett Syndrome is one of thousands of genetic disorders, it is one of four that was able to be reversed in a lab. In 2007, researchers found a way to reverse it in lab mice, giving hope to many, such as the Nues family of Danville, whose daughter Katie was diagnosed in 2003. Yet, without funding, research to safely replicate it in humans needs more research. This is why Paige Nues is hoping to win a $250,000 grant through the Pepsi Refresh Everything project.

Rett Syndrome is a developmental disorder that affects mostly girls and is realized in infancy. While born normal, symptoms begin to appear anywhere from six months to two years after birth. Eventually, the girls lose the ability to walk, speak and use their hands. Other symptoms include seizures; digestive, heart, breathing and circulation problems; and sometimes scoliosis.

According to Paige Nues, Katie is one of three girls in Danville with the disorder, as well as one of dozens in the Bay Area and one of 400 in California.

A diagnosis will likely mean a lifetime of therapies and while these girls usually live into late adulthood, they aren't capable of independent living.

"It is the most severe form of an Autism Spectrum Disorder, but what is different for our girls, is that for the most part, despite their handicaps, they are incredibly happy and social people," Paige Nues said.

The same is true for Katie Nues, who was diagnosed at 12 months and turns 8 on Sunday, July 25.

"On a day when she's feels well, and is not having seizures or stomach problems, she's bright and extroverted," Paige Nues said. "She loves being around typical kids and being in the community."

Katie is the first of three girls for Paige and her husband Jesse. The impact of the disease on the family has been huge. In order to keep up with therapy appointments and care for Katie, Paige made the difficult decision to stop working.

"It was emotionally devastating," she said. "We had what we thought was the perfect child. We thought we had done all the right things. We met, fell in love and prepared emotionally and financially to start a family. You never think it will go wrong."

Yet, even with the diagnosis, Katie is fairly strong and healthy and has a good relationship with sisters, Melissa, 4, and Abby, 2.

"They don't know her any other way, she's just their big sister," Paige Nues said. "But they definitely know she needs extra help."

One day, Paige recalls, they were headed out for a walk in the neighborhood and Melissa was starting to ride a bike with training wheels. Someone said that Katie couldn't ride a bike, but Melissa said, "Yes she can, she just needs our help." And she can, since Katie has a specialty bike just for her.

While Paige said they try not to put extra responsibilities on the other girls, she said Melissa and Abby "have amazing wisdom and sensitivity about (Katie) already."

The Nues family has been working hard to raise awareness and funds for Rett Syndrome research, so it's only fitting that they are doing all they can to get the word out about the Pepsi Refresh Everything grant. Everywhere they go, whether it they go to the grocery store or the dentist, they bring fliers and ask people to vote for the project.

Currently, "Rett Research to Reality" is in sixth place, and only first and second place receive grant money. Voting can be done daily online through July 31.

"What's intense about this campaign is that it's a cumulative daily vote," Paige Nues said. "People have to be pretty committed. You don't just need a wide network, but one of people committed to put it on their Outlook to do everyday."

With help from a private foundation in Colorado called the Pioneer Fund, they are willing to match up to $1 million to help the International Rett Syndrome Foundation. If they win, the IRSF can put $500,000 towards research.

"What (the lab test) demonstration showed is that the damage done to Katie is reversible," Paige Nues said. "It's not just a cure for newly-diagnosed patients. A cure can be found; it is possible. It's not only possible for the next generation, but it's possible to help Katie today."

Source: Danville Express

Note: Click on the title to read the full original post.

Friday, July 9, 2010

First Announcement: Annual Rett syndrome Awareness Meeting/Symposium

Dear All,

As October is "Rett syndrome Awareness Month", so we are going to organize our third "Annual Rett syndrome Awareness Meet/Symposium", which is open to everybody.

Come and Join us to Raise More Global Awareness About Rett Syndrome.

Venue and Date:
Date: Sunday, October 31, 2010
Time: 10:00am - 5:00pm
Lecture Theater-II,
Second Floor, Teaching Block,
All India Institute of Medical Sciences,
Ansari Nagar, New Delhi-110029, INDIA

Please save the date in your schedules and share this with others too and make this event a success for the cause of all Rett Angels and their families. We hope to that you will give us some of your precious time for this cause by joining us and sharing it with others.

If you have any queries, feel free to contact.


Indian Rett Syndrome Foundation

Facebook Page:!/event.php?eid=133406410027633&index=1

Thursday, July 8, 2010

Vote Pepsi Rett Research to Reality in July!

Pepsi Refresh Project

Help International Rett Syndrome Foundation Win $250K for Crucial Rett Syndrome Research Funding!
Have you voted today? IRSF is still competing to win $250K from the Pepsi Refresh Project in support of the Research to Reality Campaign for Rett syndrome research.
Today: 4th Place
Think globally, act locally & vote daily

* VOTE once a day, every day in July
o Remember: You have to sign in each time you vote (lower left hand corner)
* Sign up for Daily Email Reminders
* Visit the Research to Reality webpage under>Get Involved for more information
* Add the following statement to your email signature, blog, website and/or Facebook status page
o Please Help IRSF Win $250K for Rett Syndrome Research! think globally, act locally & vote daily
Vote for Rett syndrome once per day, every day in July
- Pepsi Refresh Project!
*Note: Get your friends involved cut & paste this message and add to your email signature

Please note that anyone 13 years of age and over can vote! Get your teenagers and their friends voting today!

Thanks, Regards, Prayers,

Indian Rett syndrome Foundation

Friday, July 2, 2010

Prolonged QT interval in Rett syndrome

C J Ellaway, G Sholler, H Leonard and J Christodoulou
Arch Dis Child 1999;80:470–472

Source: Pubmed

Rett syndrome, classical and atypical: genealogilcal support for common origin

Hans Olof Akesson, Bengt Hagberg and Jan Wahlstr6m
J Med Genet 1996;33:764-766

Source: Pubmed

Recent insights into hyperventilation from the study of Rett syndrome

Alison M Kerr and Peter O O Julu
Arch Dis Child 1999;80:384–387

Source: Pubmed

Rett Syndrome: Article by Dr. Angus Clarke

Very Interesting Review Article
Click on title to read it.

Source: Pubmed

Effect of Hand Splints on Stereotypic Hand Behavior of Girls with Rett Syndrome: A Replication Study

Helen Tuten and James Miedaner

Source: Pubmed

Hyperventilation in the awake state: potentially treatable component of Rett syndrome

Archives of Disease in Childhood, 1988, 63, 1039-1048

Source: Pubmed

Selective Cerebral Volume Reduction in Rett Syndrome: A Multiple-Approach MR Imaging Study

Interesting article by

J.C. Carter, D.C. Lanham, D. Pham, G. Bibat, S. Naidu,W.E. Kaufmann

Am J Neuroradiol 29:436–41 (Mar 2008)

Source: Pubmed

Rett Syndrome The First Forty Years: 1966–2006

Interesting article by Esteller M, 2007

Click on the title to read the article.

Source: Pubmed

Oral findings in Rett syndrome: A systematic review of the dental literature

A very interesting article by

Fuertes-González MC, Silvestre FJ, Almerich-Silla JM

Please click on the title to read the same.

Source: Pubmed

Sunday, June 13, 2010

Turn Research into Reality for 1000's of girls with Rett Syndrome

Turn Research into Reality for 1000's of girls with Rett Syndrome

Pepsi Refresh Everything.

copy and paste this link in new vindow and sign up and vote or click on the title to directly go to the site. Share it with others too.

Thanks, Regards, Prayers,

Rajni Khajuria

Friday, June 11, 2010

Slightly Early Births Linked to Autism, Dyslexia

By Kate Kelland

LONDON (Reuters) Jun 09 - Babies born just 1 or 2 weeks before their 40-week gestation due date are more likely to develop learning difficulties such as autism or dyslexia, according to a British study published on Tuesday.

The findings show that even babies born at 39 weeks have an increased risk of a developing a learning disability compared with babies born a week later.

Scientists in Scotland, analyzing the birth history of more than 400,000 schoolchildren, found that while babies born at 40 weeks have a 4% risk of learning difficulties, those born at 37 to 39 weeks of gestation have a 5.1% risk.

"There was an increasing risk of special educational needs as the gestation date fell, so as deliveries got earlier, the risk went up," said Jill Pell, an expert in public health and health policy Glasgow University, who led the study.

"Even being just a week early put the risk up."

It is already known that a baby born prematurely is more likely to have learning difficulties. But the risks for babies born in the 24 to 40 week range had not previously been studied.

Pell found that although the risk of educational difficulties was much higher in preterm than in early term babies, the absolute numbers of children with difficulties in the 37 to 39 week group were higher, because many more babies are born at this time than before 37 weeks.

In her study, early term births accounted for 5.5% percent of cases of learning disabilities, while preterm deliveries accounted for only 3.6% of cases.

According to the World Health Organization, more and more women worldwide are delivering by cesarean section and a "significant proportion" of these surgical procedures are performed without any clear medical need.

Rates of autism have also been rising, but Pell said it would be "a leap too far" to link her findings directly to rates of autism, since autism was only one of a range of learning difficulties considered.

Pell, whose study was published online June 8th in Public Library of Science (PLoS) Medicine, acknowledged that cesarean sections were not the only factor behind early-term births. But she said doctors and women should include the risks of learning difficulties when considering a cesarean.

"It is now normal policy (in cesarean section) to deliver women a week early," she said in a telephone interview. "But if you make a decision...for an elective pre-term delivery, then it has to be a balance, weighing up the risks and potential benefits.

"What this study shows is that special education needs are another factor that need to be considered."

PLoS Medicine 2010.

Source: Medscape

Wednesday, June 2, 2010

Utah scientist makes breakthrough in mental illness research

By Jennifer Stagg

SALT LAKE CITY -- It is heartbreaking to see someone you love suffer from mental illness. Now a famous Utah scientist says he's made a big breakthrough in the research to find a cure.
Doctors have traditionally treated mental illness with drugs to alter the brain's chemistry, but the University of Utah's Nobel Prize-winning geneticist Dr. Mario Capecchi tried a new approach on a lab mouse. He treated the animal for the illness the same way you would many other illnesses -- by treating its immune system.

Capecchi says compulsive behavior doesn't just affect people. In fact, he had a lab mouse who was suffering from the condition trichotillomania, where one pulls their own hair out. Scientists say it was the mouse that led to the ground-breaking discovery as they found a way to cure him.
"There's a direct correlation, in essence, between the immune system and behavior," Capecchi says.
He says scientists have known for years that there is a connection between behavior and the immune system, but they didn't quite understand it. Now he and his team have discovered it all has to do with a tiny cell called microglia.
Microglia were believed to be "scavenger cells" that would clean up damage in the brain, but Capecchi says the cells are much more powerful than they were letting on.
"What we're saying is microglia are much more sophisticated and are actually controlling behavior, and they have to do it by interacting the nerve cells in your brain," Capecchi says.

They found people and animals afflicted with behavior disorders have deformed microglia cells. So, instead of treating mental illness the way doctors traditionally have -- with medication to alter brain chemistry -- they tried a new approach by treating the immune system.
The researchers used a procedure on the mouse that's commonly practiced on cancer patients -- a bone marrow transplant.
"That cured the disease permanently, " Capecchi says. "All the hair grew back, all the lesions were healed, and the mouse no longer removes the body hair."
Capecchi says this new discovery could lead to cures for mental disorders from autism to schizophrenia.
"The book is just opened, and so there are many, many possibilities; and hopefully not only will we pursue it, but also hopefully it will interest other researchers, other investigators, to pursue similar experiments, " Capecchi says.

What are... microglia?
Microglia are immune system cells that originate in bone marrow and migrate from blood to the brain acting as the first and main form of active immune defense in the central nervous system (CNS) defending the brain and spinal cord, constantly excavating the CNS and attacking and engulfing infectious agents.


Saturday, May 29, 2010

FDA and NIH Launch Safety Reporting Web Site

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

Source: Medscape

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

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

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