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Potential treatment for Fragile X Syndrome demonstrated in fruit fly model

(Philadelphia) - Fragile X Syndrome is one of the most commonly inherited forms of mental retardation, with an incidence of 1 in 4,000 males and 1 in 8,000 females. Not many medications exist to help Fragile X patients. Now, in a fruit fly model of the disease, researchers from the University of Pennsylvania School of Medicine and their colleagues have shown that it is possible to reverse some of the symptoms of the disorder using drugs that dampen specific neuronal overactivity. Their findings appear in the March 3, 2005 issue of Neuron.

Characteristics of Fragile X in people include an average IQ of about 50, deficits in certain types of short-term memory, autistic behavior, sleep problems, hyperactivity, attention deficits, and susceptibility to seizures. In humans, Fragile X syndrome is caused by the FMR1 gene not working properly or at all. This gene encodes the FMRP protein, which controls the availability of select proteins involved in neuron-to-neuron communication.

Senior author Thomas A. Jongens, PhD, Associate Professor of Genetics at Penn, and colleagues from Albert Einstein College of Medicine and Drexel University College of Medicine, as well as other labs, have developed and characterized a Drosophila fly model for Fragile X. This model is based on mutants that lack the dfmr1 gene, which encodes a protein similar to human FMR1 protein. "Interestingly, work by my lab and others have found that the dfmr1 mutants display many physical and behavioral characteristics similar to symptoms displayed by Fragile X patients," says Jongens. These include structural defects in certain neurons, enlarged testes, failure to maintain proper day/night activity patterns; attention deficits and hyperactivity, and defects in behavior-dependent learning and memory.

"Our thinking was that since so many of the behavioral and physical phenotypes in the fly model were similar to symptoms observed in fragile X patients and a mouse fragile X model, FMR1
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
2-Mar-2005


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