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.

Small Molecule Screen Using Fragile X Neural Stem Cells

With a $90,000 grant from FRAXA Research Foundation, Dr. Peng Jin’s team from Emory University School of Medicine found that fragile X causes an increase production of new cells, so they tested large numbers of drugs to find those that can correct this. This high throughput drug screen uses neural stem cells from fragile X knockout mice to identify small molecules which may be therapeutic in fragile X.

Basic Mechanisms of Disease and Potential Therapeutic Strategies

With $245,000 in grants from FRAXA Research Foundation, Dr. Stephen Warren and his lab at Emory University studied all aspects of fragile X syndrome, from the mechanisms of repeat expansion to high-throughput drug screens in the Drosophila model of fragile X. The Warren lab made the original discovery of the fragile X gene, FMR1, in collaboration with the Nelson and Oostra labs, and is recognized internationally as a leader in molecular genetics. Recent projects include establishment of induced pluripotent stem cell lines from fragile X patients, and determination of other forms of mutation in the fragile X gene, other than the most common trinucleotide repeat expansion.