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RSRT Advisor Makes Significant Discovery with Potential for Novel Therapeutic Approaches
February 23, 2009A paper published online today in Nature Neuroscience reveals the presence of methyl CpG binding protein 2 (MeCP2) in glia. MeCP2 is a protein associated with a variety of neurological disorders, including Rett Syndrome, the most physically disabling of the autism spectrum disorders. The researchers show that MeCP2-deficient astrocytes (a subset of glia) stunt the growth of neighboring neurons. Remarkably, these neurons can recover when exposed to normal glia in culture.
The discovery was made by Gail Mandel, Ph.D. of the Vollum Institute at Oregon Health and Science University and a Howard Hughes Medical Institute investigator and Nurit Ballas, Ph.D., a research associate, at the time, in the Mandel lab at the State University of New York at Stony Brook. Dr. Mandel is a scientific advisor of the Rett Syndrome Research Trust (RSRT) a recently formed nonprofit organization intensively focused on the development of treatments and cures for Rett Syndrome and related MECP2 disorders.
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. Most live into adulthood, and require total, round the clock care. Individuals with Rett and their families suffer the emotional and financial cost of the wide range of symptoms and the ongoing struggles to address them.
Glial cells, which reside throughout the nervous system, comprise the vast majority (90%) of cells in the brain. Glia support and interact with neurons in innumerable ways, from providing the structural underpinnings and guidance of axons and dendrites (the neuronal processes that carry information), to creating protective insulation for axons. These and other glial functions are essential to the health of neurons.
Since MECP2 is located on the X chromosome, girls with Rett Syndrome are mosaic: cells with a healthy copy of the gene lie side by side with cells that have the mutated version. Mandel and colleagues found that MECP2- deficient astrocytes could not sustain normal neuronal growth. In fact, their experiments suggest that MeCP2-deficient astrocytes secrete a toxic factor that impacts the entire neighborhood of neurons, including neurons with wildtype (normal) MECP2.
Conversely, they found that wildtype astrocytes could restore the stunted growth of MeCP2-deficient neurons. This finding supports the 2007 Science publication by Professor Adrian Bird showing reversal of Rett symptoms in adult mouse models of the disorder. Results from ongoing in vivo mouse studies deleting MeCP2 in glia are promising in terms of supporting the culture studies.
"This new study adds to the growing body of evidence that glial cells are critically important contributors to neurological diseases and therefore attractive targets for drug development," said Ben Barres, Professor and Chair of the Department of Neurobiology at Stanford University and a glial cell expert.
Recent studies from multiple groups, including the lab of Dr. Tom Maniatis, a neurodegenerative disease researcher at Harvard University, have implicated glia in Lou Gehrig's disease (Amyotrophic Lateral Sclerosis - ALS), a devastating neurodegenerative disorder that leads to the death of motor neurons and total paralysis. "In Rett Syndrome, faulty glia seem to poison neurons, inhibiting growth; in ALS glia appear to release a toxic factor that kills motor neurons." Maniatis stated that "studies of the role of glia in a broad spectrum of neuronal diseases should lead to exciting advances in understanding disease mechanisms."
"Dr. Mandel's sharp insights have given the scientific community an entirely new way to think about treating Rett Syndrome. One could envision a scenario where halting the secretion of this potential toxic factor could restore health, in particular to the MECP2 positive neurons, which could bring about amelioration of symptoms. I look forward to her lab's continued contributions as we explore the therapeutic implications of her research," comments Monica Coenraads, Executive Director of RSRT and parent of a child with the disorder.
Other people who worked on the project include Daniel T. Lioy of the Vollum Institute and Christopher Grunseich, M.D. while at the State University of New York at Stony Brook. Nurit Ballas is now a Research Associate Professor in the Department of Biochemistry and Cell Biology at Stony Brook.
For more information on Rett Syndrome and MECP2 spectrum disorders please visit the website of the Rett Syndrome Research Trust at www.rsrt.org.
The Rett Syndrome Research Trust
Glial cells, which reside throughout the nervous system, comprise the vast majority (90%) of cells in the brain. Glia support and interact with neurons in innumerable ways, from providing the structural underpinnings and guidance of axons and dendrites (the neuronal processes that carry information), to creating protective insulation for axons. These and other glial functions are essential to the health of neurons.
Since MECP2 is located on the X chromosome, girls with Rett Syndrome are mosaic: cells with a healthy copy of the gene lie side by side with cells that have the mutated version. Mandel and colleagues found that MECP2- deficient astrocytes could not sustain normal neuronal growth. In fact, their experiments suggest that MeCP2-deficient astrocytes secrete a toxic factor that impacts the entire neighborhood of neurons, including neurons with wildtype (normal) MECP2.
Conversely, they found that wildtype astrocytes could restore the stunted growth of MeCP2-deficient neurons. This finding supports the 2007 Science publication by Professor Adrian Bird showing reversal of Rett symptoms in adult mouse models of the disorder. Results from ongoing in vivo mouse studies deleting MeCP2 in glia are promising in terms of supporting the culture studies.
"This new study adds to the growing body of evidence that glial cells are critically important contributors to neurological diseases and therefore attractive targets for drug development," said Ben Barres, Professor and Chair of the Department of Neurobiology at Stanford University and a glial cell expert.
Recent studies from multiple groups, including the lab of Dr. Tom Maniatis, a neurodegenerative disease researcher at Harvard University, have implicated glia in Lou Gehrig's disease (Amyotrophic Lateral Sclerosis - ALS), a devastating neurodegenerative disorder that leads to the death of motor neurons and total paralysis. "In Rett Syndrome, faulty glia seem to poison neurons, inhibiting growth; in ALS glia appear to release a toxic factor that kills motor neurons." Maniatis stated that "studies of the role of glia in a broad spectrum of neuronal diseases should lead to exciting advances in understanding disease mechanisms."
"Dr. Mandel's sharp insights have given the scientific community an entirely new way to think about treating Rett Syndrome. One could envision a scenario where halting the secretion of this potential toxic factor could restore health, in particular to the MECP2 positive neurons, which could bring about amelioration of symptoms. I look forward to her lab's continued contributions as we explore the therapeutic implications of her research," comments Monica Coenraads, Executive Director of RSRT and parent of a child with the disorder.
Other people who worked on the project include Daniel T. Lioy of the Vollum Institute and Christopher Grunseich, M.D. while at the State University of New York at Stony Brook. Nurit Ballas is now a Research Associate Professor in the Department of Biochemistry and Cell Biology at Stony Brook.
For more information on Rett Syndrome and MECP2 spectrum disorders please visit the website of the Rett Syndrome Research Trust at www.rsrt.org.
The Rett Syndrome Research Trust
Rett Syndrome Current Events and Rett Syndrome News RSSUnderstanding mental illness through gene-environment interactions
Biological Psychiatry, published by Elsevier, is very pleased to present a special section of its February 1st issue devoted to fundamental new insights into epigenetics, a field of research devoted to understanding how the environment can produce long-lasting or even heritable changes in gene function without altering the DNA sequence.
Autism Consortium members publish in PNAS: Mechanism, treatment for Rett syndrome -- top cause autism girls
The Autism Consortium, an innovative research, clinical and family collaboration dedicated to radically accelerating research and enhancing clinical care for autism spectrum disorders (ASDs), announced today that several Consortium members published a paper with significance for clinical trials in autism in the Proceedings of the National Academy of Sciences.
People with autism make more rational decisions, study shows
People with autism-related disorders are less likely to make irrational decisions, and are less influenced by gut instincts, according to research funded by the Wellcome Trust. The study adds to the growing body of research implicating altered emotional processing in autism.
Researchers find differences in swallowing mechanism of Rett syndrome patients
Researchers at Wake Forest University Baptist Medical Center have found that the reflux and swallowing problems that are common symptoms in patients with Rett syndrome and other neurological impairments, may be caused by a different mechanism than they are in healthy individuals.
Researchers link early stem cell mutation to autism
In a breakthrough scientific study published today in the Proceedings of the National Academy of Sciences, scientists at the Burnham Institute for Medical Research have shown that neural stem cell development may be linked to Autism.
Mental and physical exercise improves genetic mental impairment
Australian scientists have shown that mental and physical exercise can improve coordination and movement problems in Rett syndrome, a devastating genetic brain development disorder that primarily affects females.
Genetic analysis reveals range of Rett syndrome
The first comprehensive analysis of the clinical effects of genetic mutations involved in Rett syndrome will enable affected families to receive a more accurate indication of their child's prognosis.
Rett syndrome research reveals high fracture risk
Researchers at Perth's Telethon Institute for Child Health Research have found that girls and young women with Rett syndrome are nearly four times more likely to suffer a fracture.
Study finds first-ever genetic animal model of autism
By introducing a gene mutation in mice, investigators have created what they believe to be the first accurate model of autism not associated with a broader neuropsychiatric syndrome, according to research presented at the American College of Neuropsychopharmacology annual meeting.
Brain needs perfection in synapse number
The proper number of synapses or communication between nerve cells, determined early in life, is crucial to having a healthy brain that can learn and retain information.
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Understanding Rett Syndrome: A Practical Guide for Parents, Teachers, And Therapists by Barbro Lindberg (Author) The brand new edition of this unique book describes the difficulties and challenges of girls and women with Rett Syndrome, and proposes solutions that can help them in everyday life. Written from an educational perspective, and based on extensive practical, real-life experience, it also takes into consideration living conditions as a whole to provide practical and effective help for all those involved in the care of those with Rett Syndrome. Rett Syndrome is a severe neurological disorder with no cure affecting 1 out of every 10,000-15,000 female births worldwide. It is now known to result from a chromosomal defect that leads to problems such as mental retardation, serious motor handicaps, epileptic seizures, and difficulties with communication. This syndrome is found only in girls, and... |
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Keeping Katherine: A Mother's Journey to Acceptance by Susan Zimmermann (Author) Katherine was a beautiful, perfect baby for the first year of her life. Then, without warning, she changed forever. She started crossing her eyes. She cried at night for hours at a time and could not be soothed. She stopped saying words, stopped crawling, and began what would become a lifelong habit of wringing her hands. Hospital visits and consultations with doctors offered no answers to the mystery. Soon Katherine slipped away to a place her mother and father could never reach. In Keeping Katherine, Susan Zimmermann tells the story of her life with her daughter Katherine, who has Rett syndrome, a devastating neurological disorder. Writing with honesty and candor, Zimmermann chronicles her personal journey to accept the changed dynamic of her family; the strain of caring for a... |
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Rett Syndrome Awareness Ribbon Mouse Pad by MyHeritageWear.com The Rett Syndrome Ribbon proudly displayed on a mouse pad. There is no better way to achieve awareness for the meaning of the Rett Syndrome Ribbon than to display it on your mouse pad for everyone to see. The mouse pad measures at 9.25 x 7.75, it is machine washable, and the colors will not fade or run. Start gaining awareness today by presenting your Rett Syndrome Ribbon mouse pad at work or at home. It is certain to keep your mouse rolling in style all while gaining support and awareness! |
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Pathways to Learning in Rett Syndrome by Lewis (Author) Offering accessible advice on the special educational needs of girls with Rett syndrome, this volume aims to assist teachers in developing a working knowledge of the syndrome and suggests particular strategies in planning a curriculum which may help overcome the specific difficulties within the diagnosis. For parents, the book provides a picture of the special school system in this country and the educational implications for their daughters. It should also be of interest to those working with pupils with a more general type of profound learning disability. |
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Your Daughter Has Been Diagnosed With Rett Syndrome by Kim Isaac Greenblatt (Author) This book is for parents who just received a diagnosis of Rett Syndrome, their relatives, concerned friends and interested medical professionals. The book explains first hand reactions to the initial diagnosis as well as some coping mechanisms and suggestions for life strategies. Part of all sales go to Rett Syndrome research. Kim Isaac Greenblatt currently lives in West Hills, California. |
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The Rett Syndrome handbook: In words you can understand from those who understand by Kathy Hunter (Author) The Purpose of this publication is to circulate the most up to date information on Rett Syndrome. In words you can understand from those who understand | |
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Rett Syndrome Medical Guide by Qontro Medical Guides (Author) The Rett Syndrome Medical Guide is a publication which has been designed to better help readers understand Rett Syndrome. This Qontro Medical Guide has been designed with the reader in mind, and is a useful information source for readers at all levels looking to learn more about Rett Syndrome. The Rett Syndrome Medical Guide is highly recommended for those interested in understanding and learning more about Rett Syndrome. |
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Rett Syndrome - Clinical and Biological Aspects: Studies on 130 Swedish Females (Clinics in Developmental Medicine (Mac Keith Press)) by Bengt Hagberg (Editor) This volume provides a detailed survey of the clinical development of Rett syndrome from its earliest manifestations in childhood to adulthood. The volume surveys the developmental profile of the disease, its characteristic cluster of symptoms and signs, and categorizes the four main clinical stages in the development of motor disability. Particular emphasis is given to Rett syndrome variants and other clinical conditions which manifest themselves in a similar way to Rett syndrome. The development of scoliosis with age and disease stage is analysed. The neurophysiologic, neuropathologic and neurochemical characteristics are also examined. In addition, the volume looks at the molecular genetics of the syndrome, drug treatment and possible future developments. |
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Rett Syndrome - A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers by Philip M. Parker (Author) In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading." Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Rett syndrome is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to conduct medical research using the most advanced tools... |
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The Official Parent's Sourcebook on Rett Syndrome: A Revised and Updated Directory for the Internet Age by Icon Health Publications (Author) This book has been created for parents who have decided to make education and research an integral part of the treatment process. Although it also gives information useful to doctors, caregivers and other health professionals, it tells parents where and how to look for information covering virtually all topics related to rett syndrome (also Autism, Dementia, Ataxia, and Loss of Purposeful Hand Use), from the essentials to the most advanced areas of research. The title of this book includes the word official. This reflects the fact that the sourcebook draws from public, academic, government, and peer-reviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on rett syndrome. Given parents' increasing... |
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