Fragile X syndrome is a genetic condition that is the most common single-gene cause of autism and inherited cause of intellectual disability. In addition to mental disabilities it is also characterized by certain physical characteristics (elongated face, protruding ears, and large testes in boys), stereotypic movements such as hand-flapping, and social anxiety.
When autism is associated with Fragile X, a mutation in the Fragile X gene is responsible for the autism. (It is also possible to have autism without Fragile X, or to have Fragile X without autism.) Fragile X is a genetic disorder like Downs Syndrome, while autism is a complex behavioral disorder, likely involving multiple genetic and environmental vulnerabilities.
A new drug called arbaclofen seems to improve social avoidance and problem behaviors in adults and children with Fragile X. Researchers hypothesize that normal social stimuli overwhelm a Fragile X patient because of a defect in inhibition, and arbaclofen acting on presynaptic GABA-B receptors reduces glutamate release, thereby reducing the overactive signaling associated with this defect.
In a 6-week placebo-controlled study of arbaclofen among 63 patients with Fragile X ranging in age from 6 to 39, patients 11 years old and younger received 10mg twice a day and patients 12 and up received 10mg three times a day. The drug was well-tolerated, with only a few reports of sedation or headache. While problem social behaviors and neurobehavioral function improved, irritability did not. The study considered irritability because that is the aspect of autism most often improved by other Federal Drug Administration-approved drugs for autism, such as risperidone and aripiprazole. In another study of arbaclofen in autism spectrum disorders, it did improve irritability and agitation.
Editor’s Note: The GABA-B agonist arbaclofen has previously shown positive effects in motor spasticity. The positive effects noted here in the social domain of autism spectrum disorders and Fragile X are very promising.