Sensory hypersensibility in Fragile X Syndrome and BK Channel Openers

Silvain Briault, MD, PhD, and Jacques Pichon, PhD — University of Orleans, France

FRAXA Research Team. From left to right: Sandrine Lefeuvre (PhD, Pharmacologist), Sylvain Briault (MD, PhD, head of the team), Julie Maublanc (PhD student, Pharmacologist), Olivier Perche (PhD, hospital engineer), Béatrice Laudier (MD, PhD student), Betty Hébert (PhD student), Arnaud Menuet (PhD, assistant professor) and Jacques Pichon (Professor, Dr es Science).

Sandrine Lefeuvre, PhD, Sylvain Briault, MD, PhD, Julie Maublanc, Olivier Perche, PhD, Béatrice Laudier, Betty Hébert, Arnaud Menuet, PhD, Jacques Pichon, PhD

SUMMARY

These investigators will study sensory abnormalities in fragile X mice and test the ability of a class of drugs, BK channel openers, to rescue these abnormalities.

The team published initial results in 2014 demonstrating that the BKCa channel is a new therapeutic target for fragile X syndrome. An experimental drug, BMS-204352, rescued a broad spectrum of behavioral impairments (social, emotional and cognitive) in an animal model of fragile X.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237919/

2015  funded for $93,050

renewed in 2016 for $93,050

$90,000 in 2013
$90,000 in 2012

Presynaptic Regulator of Neuronal Excitability as Therapeutic Target for Fragile X Syndrome 

Drs. Briault and Pichon will conduct preclinical studies with selected experimental drugs which boost presynaptic regulators of neuronal excitability. Previous studies have shown that these compounds were able to improve behavior in fragile X knock-out mice. This team will further study this process in mice and in humans pluripotent stem cells.

They will also attempt to correlate their findings in mice with sensory phenotypes seen in humans with fragile X. Abnormalities of a presynaptic regulator have been reported in some children with autism. This could lead to a novel therapeutic target for treating fragile X and perhaps also some forms of autism.