Though the research is still preliminary, scientists appear to be closing in on a molecular explanation for at least some cases of autism. Research in lab animals, cadavers, and now in a small clinical trial in children seems to support the idea that autism is caused by a lack of chemical regulation in synapses, the junction between brain cells.

The latest evidence for this comes from a clinical trial of 25 autistic children ages six to 17. The trial was conducted by Seaside Therapeutics of Cambridge, Massachusetts. In unpublished data released last week, the company says the children seemed to respond well to the drug arbaclofen and suffer minimal side effects. Arbaclofen is related to the drug baclofen, a commonly used muscle relaxer and antispastic agent. The children took the drug for eight weeks, and most saw significant improvements in measures of irritability and communication, two common problems in autism.

The finding is considered preliminary because the study was not placebo-controlled, meaning scientists couldn’t compare children taking the drug to those taking a placebo. This is especially important in studies of autism because many of the tests used to assess patients are subjective, including behavioral evaluations from parents and clinicians, says Jeremy Veenstra-VanderWeele, assistant professor of psychiatry, pediatrics, and pharmacology at Vanderbilt University. About a half-dozen of his patients were involved in the trial.

Although more study is needed, Veenstra-VanderWeele says,he was pleasantly surprised by the drug’s effectiveness. One teenage patient who had benefited little from other medications was quite agitated at the beginning of the study, unable to stay in the room with investigators for more than a few minutes, Veenstra-VanderWeele says. Eight weeks later, the patient was writing notes to the investigators and seemed far less anxious and aggressive–an unusual and particularly encouraging response to a medication, says Veenstra-VanderWeele, who has no financial relationship with Seaside outside of the trial. The trial itself was funded by Seaside.

Overall, the subjects seemed to make eye contact more easily, and were less agitated and anxious, says Paul Wang, Seaside’s vice president for clinical development and a developmental-behavioral pediatrician. Some were able to interact with peers more readily and were less likely to engage in “stimming,” the repetitive rocking or banging behaviors often characteristic of autism.

Seaside has also tested arbaclofen in children with Fragile X syndrome, a genetic disorder that is often linked to autism. That trial, which was larger and placebo-controlled, showed similar positive results, according to the company. The success of the drug trials, building on other research, suggests that Fragile X is the first good molecular model for autism, says Randi Hagerman, professor of pediatrics at the University of California, Davis, and medical director of the school’s MIND Institute. Hagerman worked with Seaside on the Fragile X trial, but not on this new one.

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 GABA_B,, which inhibits neurotransmitters from being released into the synapse. It’s possible that insufficient activation of GABA_B 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 GABA_B 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.