Mechanisms of Tolerance to Chronic mGluR5 Inhibition

Over the past few years, both Novartis and Roche sponsored large-scale clinical trials of metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulators (NAMs) to treat fragile X syndrome (FXS). With a $90,000 grant from FRAXA Research Foundation in 2015-2017, Dr. Mark Bear’s team will explore if mGlu5 NAMs dosed chronically causes tolerance, and if so, how it develops and to probe new avenues to prevent or circumvent it.

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.

Repurposing Drugs to Dampen Hyperactive Nonsense-Mediated Decay in Fragile X Syndrome

With a $90,000 grant from the FRAXA Research Foundation, Dr. Lynne Maquat and Dr. Tatsuaki Kurosaki will investigate nonsense-mediated mRNA decay (NMD) in fragile X. NMD is a “housekeeping” process that cells use to prevent faulty proteins from being made. But there is too much of it in fragile X syndrome. There are already available drugs that suppress NMD – including caffeine.