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. It usually results in mental retardation and — in about half of cases — some form of autism.
Fragile X, a rare genetic disorder that causes a mutation in a gene on the X chromosome, turns off production of a regulatory protein known as FMRP, accounts for 2 percent of autism cases and affects about 1 in 4,000 boys and 1 in 8,000 girls, according to the National Institutes of Health. 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 drug known as STX209 has been tested in mice by a group of researchers that were genetically engineered to have an animal version of fragile X.
As reported in Science Translational Medicine, the tests found that it helped correct the biochemical abnormalities associated with the mutation and reduced seizures and repetitive behaviors in the mice. In another 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 expert in neurodevelopmental disorders at the University of California, Davis, MIND Institute and co-author of the human study. Dr. Randi Hagerman. “We think this is a great drug.”
The autism diagnosis has exploded over the last twenty years and therefore has been an easy target for drug development companies. Two antipsychotic medications designed for schizophrenia, have currently been approved to treat autism. But they target irritability and not its main symptoms of social dysfunction, communication problems and repetitive behaviors.
In the new study in people, there was no difference between the drug STX209, designed to treat irritability and the placebo. Researchers considered other measures, including a 12-point rating scale used to measure social avoidance in fragile X patients.
Patients improved from a mean of 4.5 to 3.3; while taking the drug the placebo,using 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.
Leader of the study, Elizabeth Berry-Kravis, a child neurologist at Rush University Medical Center in Chicago said, though the scores were similar at the end of both parts of the trial, patients made greater improvements while taking the drug.
“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.”
The Cambridge Mass.-based company that makes STX209, Seaside Therapeutics,funded the two studies. Dr. Paul Wang said the drug was being tested in two larger clinical trials for fragile X as well as a study involving 150 patients with autism.
“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.
“We need to prove — which we have not done — that this drug can help people with autism,” he said.