Frank Kooy, PhD, at University of Antwerp

Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation funded during 2014-2015, Dr. Frank Kooy and colleagues at the University of Antwerp are conducting a double blind crossover trial of ganaxolone in patients with fragile X syndrome. Results of this study were mixed (see Marinus: Results from Phase 2 Exploratory Clinical Study Support Continued Development of Ganaxolone in Fragile X Syndrome.

David Nelson, PhD, FRAXA Investigator

Fragile X Mutant Mouse Facility

With $375,000 in grants from the FRAXA Research Foundation since 2009, Dr. David Nelson has developed an impressive array of advanced mouse models of fragile X, at Baylor College of Medicine. These models are available to investigators worldwide on request. This resource has been essential for a broad, rapid distribution of fragile X and related gene mouse models and has increased the pace of fragile X research.

Dr. Tom Jongens and Dr. Sean McBride study Fragile X Fruit Flies

Fruit Flies to Model and Test Fragile X Treatments

Dr. Jongens and his collaborators have found an insulin-like protein in the fly brain that is overexpressed in the Fragile X mutant fly, leading to increased activity of the insulin signaling pathway. Furthermore, they found that certain behavioral patterns in the fragile X flies can be rescued by expressing the FX gene just in insulin producing neurons in the fly brain. In the mutant, there are other changes in the signaling pathways, including a decrease in cAMP and elevation in PI3K, mTOR, Akt and ERK activity. They now propose to study 2 medicines used for diabetes: pioglitazone (increases cAMP and decreases Akt and ERK) and metformin (inhibits mTOR), in flies and mice to validate the potential efficacy of these novel therapeutics for Fragile X.

Molly Huntsman, PhD

Cellular-Specific Therapeutic Targeting of Inhibitory Circuits in Fragile X Syndrome

Studies have shown that the function of inhibitory networks is disturbed in fragile X. This abnormality is not well understood but appears to be secondary to abnormalities in metabotropic glutamate and endocannabinoid systems. With a $90,000 grant from FRAXA in 2013-2014, Dr. Molly Huntsman’s team examined how these networks interact and how inhibitory deficits can best be remedied.

Computational Analysis of Neural Circuit Disruption in Fragile X Model Mice

Computer modeling of the brain offers the hope of predicting how the brain responds to varying conditions, but these models have been rather primitive until recently. The Sejnowski team at the Salk Institute, who specialize in computational models of neural networks, will take the results of previous FRAXA-funded projects and incorporate them into their advanced computer models of brain function.