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.
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.
Natalie Farny, PhD
FRAXA Postdoctoral Fellow