Correcting Fragile X Syndrome by Inhibiting the Synaptic RNA-Binding Protein CPEB1

The Richter lab is the foremost research group in the world in the study of CPEB, a protein critical for regulation of protein synthesis. With $170,000 in grants from FRAXA Research Foundation over 2008-2011, Dr. Joel Richter of the University of MA Medical School explored whether inhibitions of the CPEB may be a viable approach for treatment of fragile X.

Joel Richter, PhD
$170,000 Grant
Joel Richter, PhD
Principal Investigator
University of MA Medical School
2008-2011 FRAXA Research Grant
$170,000 over 4 Years

CPEB and FMRP are two translational regulatory proteins found at postsynaptic and other sites in the brain. Thinking that a functional interaction between the two proteins might influence characteristics associated with the Fragile X Syndrome, we generated FMRP/CPEB double knockout mice (DKO). These animals, as well as wild type (WT), FMRP KO, and CPEB KO mice were subjected to a battery of behavioral tests. In addition, we tested brain tissue from the four genotypes for synaptic function and protein synthesis. We found that many behaviors typically considered to be fragile X syndrome-associated in FMRP KO mice were corrected in the DKO animals. Moreover, the synaptic deregulation and aberrantly high protein synthesis found in FMRP KO mice were also corrected in the DKO animals.

These data suggest that CPEB might be a suitable target for therapies aimed at ameliorating the Fragile X Syndrome. We are investigating this possibility and working to understand the molecular basis of the FMRP-CPEB interaction.

November 2014: NIH awards Richter $9.5 million for Fragile X research center

Five year, collaborative grant will be used to investigate the underlying basis of Fragile X syndrome at UMass Medical School

Natalie Farny, PhD
FRAXA Postdoctoral Fellow