Autism Consortium Scientists Publish Study Defining Mechanism and Potential Treatment for Rett Syndrome, Leading Cause of Autism in Girls

February 11, 2009

- Clinical trial to test molecule in humans is being planned - - Data in PNAS reveals therapeutic that could apply to other forms of autism -

BOSTON - JANUARY 9, 2009 - 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 Science.

The research led by Autism Consortium members Mriganka Sur, PhD, Newton Professor of Neuroscience at the Picower Institute and Head of the MIT Department of Brain and Cognitive Sciences; and Rudolf Jaenisch, PhD, Founding Member, Whitehead Institute and Professor of Biology at MIT, demonstrates for the first time a mechanism for Rett Syndrome and a therapeutic that could be directly applicable to humans. As a result, a clinical trial in humans is in development.

IGF1 Reverses Rett Symptoms in Mice; Clinical Trial Planned This groundbreaking study demonstrated that by treating mice with a peptide fragment of IGF1, a molecule that is utilized by the brain for neuronal and synaptic development, the symptoms of Rett Syndrome in the mice were largely reversed.

"The next step is to test recombinant human IGF1 which is already available for pediatric use in humans with the hope of treating or reversing Rett Syndrome," said Omar Khwaja, MD, PhD, Director of the Rett Syndrome Program at Children's Hospital Boston and head of the clinical trial team for IGF1. "We are working as quickly possible to develop the protocol, secure funding, and initiate the trial."

"This new study presents promising novel data suggesting that targeting the IGF1 signaling axis may present a useful therapeutic strategy that could ultimately be translated to humans." said Dr. Antony Horton, Chief Scientific Officer at the International Rett Syndrome Foundation. "We are encouraged by this collaboration between scientists and clinicians which is yielding valuable insights into potential new treatments for Rett syndrome."

About Rett Syndrome and the Findings
Rett Syndrome, a neurodevelopmental disorder mainly affecting girls and also the most common basis of autism in girls, is primarily caused by a sporadic mutation in the MECP2 gene on the X chromosome. The MECP2 gene makes a protein, also called MeCP2, believed to play a pivotal role in silencing, i.e. turning off the activity of other genes. The MECP2 mutation causes the regulatory mechanism to fail, which in turn causes other genes to function abnormally.

Rett is a genetic disorder of developmental arrest or failure of brain maturation. This is thought to occur when subsets of neurons and their connections (synapses) are disrupted during a very dynamic phase of brain development. Scientists have been investigating ways to reverse that arrest and therefore, turn brain activity back on.

By crossing into the brain and activating 'IGF1 signaling' - IGF1 binds to its receptor and activates downstream molecules within neurons that make synapses mature. This activity in turn ends the developmental arrest thought to underlie the syndrome.

Using mutant mice in which MeCP2 is deleted, Sur and his co-authors demonstrated a major underlying mechanism for the disorderâ€"synapses in the brain remain immature and showed persistent, abnormal plasticity into adulthood.

"Our research is beginning to show that other forms of autism also have, as their basis, this persistent immaturity of synapses," said Sur. "As a result, an even more exciting and promising aspect of this work is the possibility that IGF1 or similar therapeutics could apply not only to autism caused by Rett Syndrome, but also to other causes of autism as well."

In addition to Sur and Jaenisch, the study's authors are postdoctoral fellows Daniela Tropea, Nathan R. Wilson and Cortina McCurry at the Picower Institute; and Emanuela Giacometti, Caroline Beard, Dong Dong Fu and Ruth Flannery at the Whitehead Institute.

About the Autism Consortium:
The Autism Consortium is a scientific and clinical collaboration that includes 12 Boston area institutions, supported by a non-profit that is dedicated to facilitating and funding research and improving clinical care. The Consortium's mission is to support a disease-based collaboration dedicated to rapidly advancing the understanding, diagnosis, and treatment of autism through collaborative research to improve the care of children and families affected by autism and related disorders. The Consortium brings together the best minds across Boston from Beth Israel Deaconess Medical Center, Boston Medical Center, Boston University, Boston University School of Medicine, Broad Institute of MIT and Harvard, Children's Hospital Boston, Harvard University, Harvard Medical School, Massachusetts General Hospital, Massachusetts Institute of Technology, The Floating Hospital for Children at Tufts Medical Center and the University of Massachusetts Memorial Medical Center.

To learn more about the Autism Consortium, please visit www.autismconsortium.org.

About the Picower Institute
The Picower Institute for Learning and Memory is an independent research entity within MIT's School of Science, with faculty members holding academic appointments in the Department of Brain and Cognitive Sciences, the Department of Biology, or both. The Institute also offers exciting research opportunities for scholars at all levels, from undergraduates to post-docs.

In 1994, MIT first established a world-class, multidisciplinary neuroscience research center, initially with a grant from the Sherman Fairchild Foundation and, more recently, with long-term support from the RIKEN Brain Science Institute and the National Institute of Mental Health. In 2002, thanks to an extraordinary gift from the Picower Foundation, the Center became the Picower Institute for Learning and Memory.

About the Whitehead Institute for Biomedical Research
Whitehead Institute for Biomedical Research is a leading, nonprofit research and educational institution that has defined the cutting edge of biomedical science, creating a legacy of research excellence and academic eminence since 1982. Wholly independent in its governance, finances and research programs, Whitehead shares a teaching affiliation with Massachusetts Institute of Technology (MIT), offering the intellectual, collegial and scientific benefits of a leading research university.

Whitehead provides scientists with the resources and freedom to follow their scientific instincts, form novel collaborations and conduct high-risk research. While probing basic biological processes, 14 faculty Members and 6 Fellows develop innovative technologies and lay the foundation for projects that improve human health. They run pioneering programs in cancer research, immunology, developmental biology, stem cell research, regenerative medicine, genetics and genomicsâ€"programs with a record of success.

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