Treatment for One Form of Autism on the Horizon?

Could there be a true treatment for autism on the horizon? According to a new research study conducted at the Massachusetts Institute of Technology , the form of autism known as Fragile X syndrome may be treatable by blocking the expression of a single gene.

Fragile X syndrome (FXS) is the most common cause for mental retardation and autism, and affects between 90,000 and 100,000 people in the United States. FXS is caused by a mutation in FMR1 gene carried on the X chromosome, which produces a single protein called FMRP. The mutated gene prevents the formation of FMRP, which in turn causes the symptoms of FXS.

The team led by Howard Hughes Medical Institute investigator Mark Bear theorized that perhaps it was not the lack of the protein FMRP that caused the problem, and looked to one of the other brain proteins it regulates, metabotropic glutamate receptor-5 (mGluR5), which turns on protein synthesis. FMRP, on the other hand, turns off protein synthesis, but in a fragile X case, no FMRP is being produced. Work was conducted at the Massachusetts Institute of Technology's Picower Institute for Learning and Memory and at Brown Medical School, India's National Institute of Mental Health and Neuroscience, and the Tata Institute of Fundamental Research in Bangalore, India.

In a press release from Howard Hughes Medical Institute, Bear said "The theory was that when FMRP was removed, protein synthesis was placed on a hair trigger, and that many pathologies of fragile X might be a consequence of that increase in protein synthesis," he said. "The most exciting consequence of that theory was that it might be possible to correct fragile X by dialing back mGluR5 activation."

When FMRP is not present, an excessive number of neuronal connections and dendrites are formed in the brain, in essence creating too many connections and a 'short circuit' of the brain's wiring.

The study, which appeared in the journal Neuron, showed that by partially blocking the expression of the mGluR5 protein in mice that the effects of the mutated gene could be regulated, and the mental retardation and autism reversed. The symptoms of fragile X syndrome include mental retardation, autism, seizures, and abnormally rapid growth.

Bear and his team are now searching for which other brain proteins are being controlled by FMRP and mGluR5. Bear said they hope "a significant fraction of cases of autism might be accounted for by excessive cerebral protein synthesis. If that were true, then mGluR5 antagonists might be therapeutically useful for much more than just fragile X."

Principal author of the paper was Brown University graduate student Dül Golen. Co-authors were Picower Institute postdoctoral fellow Emily Osterweil; B.S. Shankaranarayana Rao of the National Institute of Mental Health and Neuroscience in India; MIT graduate students Gordon B. Smith and Benjamin D. Auerbach; and Sumantra Chattarji of the National Center for Biological Sciences and Tata Institute of Fundamental Research in India.