Until now, attempts at treating autism have been limited to drugs that target peripheral symptoms such as anxiety, aggression and repetitive behaviors. But researchers hope that data from a crop of new drugs in development will allow them, for the first time, to treat an underlying mechanism of the condition, potentially helping those with autism to communicate.

The majority of autism cases are idiopathic, meaning that researchers have yet to understand their cause. But some animal studies of autism have pointed to signaling problems in the brain. Targeting those signaling problems, some researchers think, may ameliorate autism symptoms once thought to be intractable.

Researchers have gleaned some of this information by studying a handful of diseases caused by single-gene glitches that can result in autism. Such disorders account for about 15 to 20 percent of autism cases, says Geraldine Dawson, scientific director of Autism Speaks. In fragile X, which causes autism in a significant number of cases, the points of contact between neurons contain too much glutamate, a chemical messenger that transmits excitatory signals. “There's an optimal level of activation” in the brain, and this equilibrium is disrupted in fragile X, explains Randall L. Carpenter, co-founder and CEO of Cambridge, Mass.–based biotech firm Seaside Therapeutics. The company is developing drugs that aim to rebalance levels of excitatory and inhibitory messengers, known as neurotransmitters. Hitting that sweet spot may allow the brain to develop the necessary connections for weeding out background noise and focusing on important information, Carpenter says. That, in turn, might allow patients to feel less overwhelmed by sensory stimuli and to have an easier time interacting with others.

Yet do those with idiopathic autism suffer from that same glutamate imbalance? That is what Seaside is working to find out. The company's most advanced drug, arbaclofen, dampens glutamate activity and has reversed some symptoms in mouse models of fragile X. Data so far also suggest some benefits in humans. “The big question is whether these same drugs can address symptoms in people with idiopathic autism,” Dawson says. Seaside's study exploring that question is due out later this year. If arbaclofen works in at least some of these individuals, that finding would offer the first evidence that certain cases of idiopathic autism share the same well-studied neurobiological flaws as single-gene permutations of autism. More important, it would show, for the first time, that autism is treatable with drugs. “That will be a watershed moment,” Dawson says.

Still, big questions remain. Thus far, researchers have had little success designing drugs that target glutamate without side effects. And should the drugs work, researchers will still need to determine at what age they would be most beneficial, because autism begins early in development. But the results of Seaside's trials and those of similar drugs in the pipeline, Dawson says, “are going to be a huge step to understanding what the path to discovery is going to be.”

FURTHER READINGS AND CITATIONS ScientificAmerican.com/nov2012/advances