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RSRF-funded study leads to breakthrough for Rett Syndrome research

A collaborative study between the laboratories of Michael Greenberg of Children's Hospital Boston and Rudolf Jaenisch of the Whitehead Institute of Biomedical Research has resulted in a significant breakthrough. The investigators report in the October 31, 2003 issue of the prestigious journal Science, that the "Rett Syndrome gene", MECP2, regulates expression of the gene encoding brain-derived-neurotrophic factor (BDNF). The study was funded, in part, by the Rett Syndrome Research Foundation (RSRF). A paper by Yi Sun and colleagues of UCLA published in the same issue further corroborates Greenberg's and Janenisch's findings.

Rett Syndrome is a devastating neurological disorder diagnosed almost exclusively in girls. Children with Rett Syndrome (RTT) appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and extreme motor control problems. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure.

Although the protein implicated in RTT, MeCP2, is known, its precise function is not. Past experiments have demonstrated that MeCP2, acting like a biological deadbolt, binds to genes that have undergone methylation (a fundamental biological process in which the cell disables genes it doesn't use by modifying them with a methyl group) preventing them from activating. As a result, scientists theorized that MeCP2 was a "long-range gene repressor."

Jaenisch's lab, with RSRF funding, demonstrated that when MeCP2 is disabled in mice, the animals manifest Rett-like symptoms. The next step was to figure out why this happens and what genes MeCP2 targets.

Concurrently, Greenberg, who is also a professor of neurobiology at Harvard Medical School, was studying a central nervous system gene, BDNF, which is highly active in infants aged 6 t
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Contact: Monica Coenraads
monica@rsrf.org
203-445-9233
Rett Syndrome Research Foundation
30-Oct-2003


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