Re: / Rett Syndrome Study leading to human clinical trials

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Rett Syndrome: Study Suggests Molecule Can Reverse Some Symptoms

11 Feb 2009

A molecule that promotes brain development could serve as a possible

treatment for Rett syndrome, the most common form of autism in girls,

according to researchers at MIT's Picower Institute for Learning and Memory

and the Whitehead Institute for Biomedical Research.

The researchers found that injecting the molecule into mice that have an

equivalent of Rett syndrome helped the animals' faulty brain cells develop

normally and reversed some of the disorder's symptoms.

The work, reported in the Feb. 10 online edition of the Proceedings of the

National Academy of Sciences (PNAS), is expected to lead to new human

clinical trials for a derivative of growth factor-1 (IGF-1), currently used

to treat growth disorders and control blood glucose. The MIT study indicates

that IGF-1 could potentially lessen the severity of symptoms of Rett

syndrome.

" We demonstrate that a major underlying mechanism behind Rett syndrome in

mice is that synapses in the brain remain immature and show persistent,

abnormal plasticity into adulthood, " said a Tropea, a postdoctoral

fellow at the Picower Institute and lead author of the study. " We also

propose that a therapeutic based on this mechanism would be directly

applicable to humans. "

Injecting mice with a peptide fragment of IGF-1, used by the brain for

neuronal and synaptic development, reverses a large number of symptoms of

mice genetically engineered to display Rett syndrome-like symptoms.

" IGF-1 is critical for brain development. It activates molecules within

neurons that make synapses mature, " said study co-author Mriganka Sur, the

Newton Professor of Neuroscience at the Picower Institute and head of the

MIT Department of Brain and Cognitive Sciences. " This is a mechanism-based

therapeutic for Rett syndrome. It is possible that this or similar

therapeutics would apply to other forms of autism, which also have as their

basis a persistent immaturity of synapses. "

HELPING NERVE CELLS MATURE

Rett syndrome, an inherited neurological disorder, causes loss of speech,

reduced head size, breathing and heart abnormalities and autism-like

symptoms in one out of 10,000 girls.

In 85 percent of girls with Rett syndrome, the culprit is a faulty gene

coding for methyl CpG-binding protein 2, (MeCP2), critical for nerve cell

maturation. A deficit in MeCP2 stops neurons from growing spines, the

branch-like projections needed for cell-to-cell communication.

Recent genetic studies have shown that increasing MeCP2 expression in mice

led neurons to grow new spines, indicating that the disease could be

reversible. Increased IGF-1 seems to make up for the lack of MeCP2.

Daily injections of the insulin-like growth factor IGF-1 extended the life

spans of infant Rett syndrome mice, improved their motor function and

breathing patterns and reduced irregularities in their heart rates. In

addition, their brains had more nerve-cell spines.

IGF-1 affects almost every cell in the human body, especially in muscle,

cartilage, bone, liver, kidney, nerves, skin and lungs. In addition to its

insulin-like effects, IGF-1 also regulates cell growth and development in

nerve cells.

" This is the first realistic way for a drug-like molecule injected into the

bloodstream to relieve Rett syndrome symptoms, " said Whitehead member Rudolf

Jaenisch, whose lab participated in the research.

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Article adapted by Medical News Today from original press release.

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