A boy with autism interacts with a video game during his testing at UNT Center… (Max Faulkner / Fort Worth…)
An experimental drug can improve sociability in patients with fragile X syndrome and may be helpful as a treatment for autism, according to the authors of a new study.
Fragile X is a rare genetic disorder that affects about 1 in 4,000 boys and 1 in 8,000 girls, according to the National Institutes of Health. It usually results in mental retardation and — in about half of cases — some form of autism.
In fragile X, which accounts for 2% of autism cases, a mutation in a gene on the X chromosome turns off production of a regulatory protein known as FMRP. That leads to out-of-control activation of the brain chemical glutamate, which plays a key role in learning and memory, potentially explaining social anxiety and other symptoms of the disorder.
A group of researchers tested a drug known as STX209 in mice that were genetically engineered to have an animal version of fragile X. The researchers found that it helped correct the biochemical abnormalities associated with the mutation and reduced seizures and repetitive behaviors in the mice, they reported Wednesday in the journal Science Translational Medicine.
In a related study published in the same journal, 46 children and 17 adults with fragile X were assigned to take the drug for four weeks and a placebo for four weeks. Patients made bigger improvements on a "social avoidance" scale while they were taking the drug compared with when they were taking the placebo.
"This study nails a core feature in autism," said Dr. Randi Hagerman, an expert in neurodevelopmental disorders at the UC Davis MIND Institute and coauthor of the human study. "We think this is a great drug."
But scientists who were not involved in the study said the improvements were modest at best and that their applicability to autism — a highly variable disorder that may have many distinct causes — was unclear.
"The data have to be viewed with extreme caution," said Dr. Christopher McDougle, a psychiatrist and autism expert at Harvard University. "They're interesting. That's about all you can say."
An explosion in autism diagnosis over the last two decades makes the disorder an obvious target for drug developers. But with little understanding of its biological underpinnings, researchers have not known which chemical pathways to focus on.
Two drugs, both antipsychotic medications designed for schizophrenia, are currently approved to treat autism. But they target irritability and not its hallmark symptoms of social dysfunction, communication problems and repetitive behaviors.
The new study in people was designed to measure the effect of STX209 on irritability, but there was no difference between the drug and the placebo. So the researchers considered a variety of other measures, including a 12-point rating scale used to measure social avoidance in fragile X patients.
During treatment with the drug, patients improved from a mean of 4.5 to 3.3; while taking the placebo, they went from 3.9 to 3.6. Patients, their families and the doctors assessing them did not know when they were getting the drug and when they were on the placebo.
Though the scores were similar at the end of both parts of the trial, patients made greater improvements while taking the drug, said study leader Elizabeth Berry-Kravis, a child neurologist at Rush University Medical Center in Chicago.
"They're willing to go out in public," she said, describing reports from patients' parents. "They're willing to come downstairs. They're willing to stay at a birthday party. They're willing to go to a dentist."
Outside experts warned that the social impairments in fragile X may be unique to that disorder.
"I would be cautious in concluding this drug is effective for the social deficits of autism on the basis of this study," said Larry Scahill, a drug researcher at Yale University.
Seaside Therapeutics, the Cambridge, Mass.-based company that makes STX209, funded the two studies. Dr. Paul Wang, an executive at the company, said the drug was being tested in two larger clinical trials for fragile X as well as a study involving 150 patients with autism.
"We need to prove — which we have not done — that this drug can help people with autism," he said.