Modulator of mGluR5 Improves Features of Autism in Mice

GRN-529 reduces repetitive behaviors and partially reverses lack of sociability

THURSDAY, April 26 (HealthDay News) -- A selective negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5), GRN-529, improves some behavioral features of autism in mouse models of the disorder, according to an experimental study published in the April 25 issue of Science Translational Medicine.

Noting that inhibitors of the mGluR5 are in clinical trials for fragile X syndrome, and about 30 percent of these patients have autism, Jill L. Silverman, Ph.D., from the National Institute of Mental Health in Bethesda, Md., and colleagues examined the efficacy of the mGluR5 inhibitor GRN-529 in an established mouse model with behavioral phenotypes relevant to the three diagnostic behavioral symptoms of autism (BTBR).

In BTBR mice, the researchers found that, at non-sedating doses, GRN-529 reduced repetitive behaviors and partially reversed lack of sociability on some measures of social approach and reciprocal social interactions. However, GRN-529 did not improve impaired communication in the mice. In a second inbred strain of mice, the same non-sedating doses reduced the characteristic, spontaneous stereotyped jumping.

"These findings raise the possibility that a single targeted pharmacological intervention may alleviate multiple diagnostic behavioral symptoms of autism," Silverman and colleagues conclude.

The study was partly funded by Pfizer; several authors are employees of Pfizer.

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