Hope For Eliminating Mental Retardation

The results of a test in mice offer hope for a way to treat fragile X syndrome, the most common form of inherited mental retardation and the leading known cause of autism. No treatment is currently available for the syndrome.

The condition is caused by a mutation in the gene for fragile X mental retardation protein (FMRP). Howard Hughes Medical Institute investigator Mark F. Bear, a neuroscientist at Massachusetts Institute of Technology, and his colleagues surmised that FMRP normally restrains production of other proteins in the brain. In this way, FMRP counteracts the activity of mGluR5, a??glutamate receptor??that turns on protein synthesis. The researchers reasoned that loss of functional FMRP upsets the normal balance achieved between mGluR5 and FMRP and leads to excessive protein synthesis.

Working with mice that replicate fragile X syndrome, Bear and his colleagues introduced mutations that reduce mGluR5 expression and showed that these prevent symptoms of retardation and autism. The results indicate that the receptor has a key role in the disease and that drugs that block this receptor could conceivably be used to treat the condition (Neuron 2007, 56, 955).

Bear founded the company Seaside Therapeutics to study mGluR5-targeted drugs as therapeutics for fragile X syndrome. He also wants to identify the particular brain proteins that are regulated by FMRP and mGluR5 so treatments can be targeted even more precisely.