Correcting Fragile X Syndrome Deficits by Targeting Neonatal PKCε Signaling in the Brain
Richard Jope, PhD
Margaret King, PhD
FRAXA Postdoctoral Fellow
University of Miami
2008-2009 Grant Funding: $100,000
2011-2012 Grant Funding: $108,000
With $208,000 in funds from FRAXA Research Foundation, Dr. Richard Jope and his team at the University of Miami tested whether inhibitors of GSK3 can reduce abnormalities in Fragile X mice.
Dr. Richard Jope demonstrated the potential of GSK3 inhibitors, including the available drug lithium, to reverse cognitive deficits in Fragile X in mice.
Dr. Jope’s lab showed that both lithium (at usual therapeutic doses) and investigational GSK3 inhibitors can reverse a number of cognitive deficits in FMR1 knockout mice. Moreover, the Jope group showed that Fragile X mice are abnormal in novel object recognition, spatial memory, and temporal order memory, and that these GSK3-inhibiting compounds could all reverse these defects, along with associated electrophysiological abnormalities.
Dr. Jope won the 2013 FRAXA Pioneer Award for this work.
Results were published in Genes Brain & Behavior: Lithium treatment alleviates impaired cognition in a mouse model of fragile X syndrome on August 2013.
Preliminary evidence raised the possibility that lithium may be therapeutically beneficial for Fragile X. This project tested if the therapeutic target of lithium is inhibition of the enzyme GSK3 by testing if newly developed, highly specific inhibitors of GSK3 reduce behavioral abnormalities in Fragile X mice. Such a finding would support further development of many new GSK3 inhibitors that have been developed by pharmaceutical companies and justify their testing for a Fragile X indication.