Developing drug treatments for autism has proved very challenging, in part because it’s not yet clear what causes it. The symptoms of the disorder vary highly from person to person, and it cannot be diagnosed with a blood test or brain scan. Arbaclofen is one of only a few drugs that has shown a benefit.
The drug works by increasing production of an amino acid, called GABAB,, which inhibits neurotransmitters from being released into the synapse. It’s possible that insufficient activation of GABAB in the synapses of cells in a specific part of the brain, leads to the excessive anxiety often seen in people with autism and Fragile X, says Seaside president, CEO, and cofounder Randall Carpenter.
Recent research on autopsies of people with autism showed that they have fewer GABAB receptors compared to controls. And studies of rodents designed to genetically mimic the defects in Fragile X support the idea that augmenting activity of the receptors helps relieve symptoms of the disorder, Carpenter says.
It’s still too early to predict whether the drug will prove successful in larger clinical studies, and if so, at what age treatment should begin. The company has only tested it in children over six years old because that is the age range for drugs now used to treat irritability in autistic children. Carpenter says he hopes it will eventually prove more effective in younger children by helping them avoid years of deficits, and will also work in adults with autism, because the synaptic damage does not appear to be irreversible. It’s also unclear, Carpenter says, whether the drug will need to be taken for a short period, to reprogram and retrain brain circuits, or whether patients will need to take it indefinitely.
Investigators were somewhat concerned before the study that activating the GABA receptors might simply sedate the children, says Wang. (Benzodiazepines, such as Valium, which are used as antianxiety agents and sleep aids, act on another type of GABA receptor.) But reports from doctors, plus the improvements seen in communication as well as irritability, suggest that sedation was not an issue, he says. Next, Seaside hopes to advance its Fragile X research, and to conduct a larger, placebo-controlled trial on children with autism, Wang says.