News

Clinical Tests Begin on Medication to Correct Fragile X Defect

NIH-supported scientists at Seaside Therapeutics in Cambridge, MA, are beginning a clinical trial of a potential medication designed to correct a central neurochemical defect underlying Fragile X syndrome, the most common inherited cause of intellectual disability.  There has to date been no medication that could alter the disorder's neurologic abnormalities. The study will evaluate safety, tolerability, and optimal dosage in healthy volunteers.

The work is the outcome of basic research that traced how an error in the fragile X mental retardation gene (FMR1) leads to changes in brain synapses.  The changes in turn appear to be the mechanism for learning deficits in Fragile X syndrome.  The new trial tests Seaside Therapeutics' novel compound, STX107, that selectively and potently targets the synaptic defect.

Thomas R. Insel, MD, director of the National Institute of Mental Health, says, "This project is the culmination of years of fundamental research, first identifying the genetic mutation and later deciphering the biochemical consequences of this mutation.  Now, with the initiation of this first clinical study, we move one step closer to understanding how this novel candidate may play a critical role in improving the lives of individuals with Fragile X Syndrome."

People with Fragile X have DNA mutations in the FMR1 gene that, in effect, turn off the gene.  Research in recent years has identified the molecular consequences of this silencing of FMR1.  Normally, the protein product of the FMR1 gene acts to dampen the synthesis of proteins at synapses that are stimulated via a specific class of receptors on brain cells—metabotropic glutamate receptors. Without the brake provided by FMR protein, synaptic protein synthesis is excessive and connections do not develop normally.

— Source: National Institute of Mental Health