Genetic and Pharmacologic Manipulation of PI3K Activity in FXS: Assessing Potential Therapeutic Value

Dr. Bassell’s team has developed powerful molecular genetic techniques to track mRNAs and FMRP particles as they move through these processes in brain tissue from fragile X knockout mice. They have shown that a specific intracellular signaling pathway, the PI3K/mTOR pathway, is overactive in the absence of FMRP. This pathway is involved in mediating many neuronal neurotransmitter receptors. This project will test new drugs in development which inhibit an enzyme known as PI3 kinase, a part of the pathway, and have the potential to normalize neuronal function in fragile X.

Efficient Screening for Pharmaceutical Amelioration of FXS Behavioral Deficits in Drosophila

With a $112,250 grant from FRAXA Research Foundation over 3 years, Dr. Efthimios Skoulakis and his team from the Institute of Cellular and Developmental Biology conducted the first FRAXA project in Greece, where they developed a speedy new test for learning problems in fruit flies, which allowed them to test a number of drugs that are potential fragile X treatments.

Manipulating Basal and mGluR-Stimulated cAMP Level in FXS Model Mice

With a $90,000 grant from FRAXA Research Foundation, Dr. Hongbing Wang’s team from Michigan State University looked at a treatment target “downstream” of the mGluR5 called cyclic AMP (cAMP). Levels of cAMP are lower in FXS patients and animal models, suggesting that it plays a role in FXS. Drugs that raise levels of cAMP may effectively treat fragile X. We are very pleased to report that, in 2012, Dr. Wang received a 5-year, $250,000 per year R01 grant from NIH to continue this promising research.