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Jun 26, 2007

MIT Team Reverses Symptoms of Mental Retardation in Mice

  • Researchers at the Picower Institute for Learning and Memory at MIT report that they have, for the first time, reversed symptoms of mental retardation and autism in mice.

    "Our study suggests that inhibiting a certain enzyme in the brain could be an effective therapy for countering the debilitating symptoms of FXS (Fragile X Syndrome) in children and possibly in autistic kids as well," remarks co-author Mansuo L. Hayashi, a former Picower Institute postdoctoral fellow currently at Merck Research Laboratories in Boston.

    The team studied mice genetically manipulated to model Fragile X Syndrome (FXS). They observed that the enzyme called p21-activated kinase, or PAK, affects the number, size, and shape of connections between neurons in the brain. Halting PAK's enzymatic activity reversed the structural abnormality of neuronal connections found in the FXS mice, reports co-author Susumu Tonegawa, Picower professor of biology and neuroscience. Stopping PAK also reversed abnormalities in spine number and structure.

    "PAK inhibition also restored electrical communication between neurons in the brains of the FXS mice, correcting their behavioral abnormalities in the process," points out Tonegawa.

    "Notably, due to an elegant genetic manipulation method employed by the Picower Institute researchers, PAK inhibition in the FXS mice did not take place until a few weeks after appearance of disease symptoms,” Tonegawa adds. “This implies that future treatment may still be effective even after symptoms are already pronounced."

    "While future studies will be necessary to further characterize the precise molecular nature of the interaction between PAK and FMR1, our findings clearly demonstrate that PAK inhibition can counteract several key cellular and behavioral symptoms of FXS," the authors noted. The work was reported in the online early edition of PNAS the week of June 25-29.



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