Sean McBride, PhD—Albert Einstein College of Medicine
Treatment for Fragile X in Fruit Flies and Mice

Sean McBride, PhD, Principal Investigator
Catherine Choi, Co-Investigator
Tom Jongens, PhD, Co-Investigator

FRAXA Awards:

$120,000 in 2009
$120,000 in 2008
$70,000 in 2006
$70,000 in 2005


One of the most important aspects of FRAXA's research is the preclinical validation of potential therapeutic strategies. Many different labs have shown the ability to make significant breakthroughs, finding new leads for treatment. However, very few have the capacity to test new drugs in the mouse model to establish efficacy rigorously enough to lead to clinical trials. The McBride lab (in a broad collaboration with the Choi, Jongens, and Skoulakis groups) specializes in testing especially promising compounds in the fragile X knockout mouse, to enable clinical trials in people with fragile X.
Examining Cognitive Dysfunction in the Drosophila Model of Fragile X Syndrome

by Michael Tranfaglia, FRAXA, 1/1/2006

Fragile X Syndrome is the most common inherited form of mental retardation, but few medications exist to help Fragile X patients. In a fruit fly model of the disease, researchers from the University of Pennsylvania School of Medicine and their colleagues have shown that it is possible to reverse some of the symptoms of the disorder using drugs that dampen specific neuronal overactivity. Their findings appeared in the March 3, 2005 issue of Neuron, and in Newsweek Magazine.

Their work in flies indicates that antagonizing mGluR signaling may be a potential pharmacologic strategy.

With further funding from FRAXA, Sean McBride and colleagues are now performing biochemical studies to investigate the effects of these treatments on levels of relevant proteins, to fully understand how these drugs are having their effects. They will characterize the cognitive phenotypes in fragile X flies as they age. They will evaluate learning and memory of aged Drosophila to determine if prolonged treatments that restore memory in young adulthood continue to be effective in elderly flies. Already they have preliminary evidence of increased cognitive deficits in older fragile X flies and that these deficits can be prevented with drug treatments.

They are also investigating the effects of these treatments in FMR1 knockout mice, specifically studying the effects of mGluR antagonists, lithium,and other drugs, on the enhanced mGluR-dependent long-term depression phenotype in the fragile X mice.