An experimental drug showed promising results in treating the key symptom of social withdrawal in people with Fragile X syndrome, the most common known inherited cause of autism with intellectual disability, according to a recent clinical trial.
The drug, known as arbaclofen or STX209, is a derivative of the FDA-approved drug, baclofen, which is primarily used to treat muscle spasticity in conditions like cerebral palsy and is being studied as a treatment for alcoholism and other addictions.
The new study, published in Science Translational Medicine, hints that arbaclofen could be the first drug to treat symptoms of Fragile X and other autism spectrum disorders, and even other conditions involving social avoidance. This is an important trial, says Eric Hollander, director of the autism and obsessive compulsive spectrum disorder program at Montefiore/Albert Einstein School of Medicine in New York, who was not associated with the study. It should be of interest to the entire field of neurodevelopmental disorders, he says.
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Fragile X syndrome is caused by a defect in the FMR1 gene, located on the X chromosome. It is the most common inherited cause of intellectual disability, particularly in boys, who are harder hit because they have only one X chromosome. In addition to intellectual disability, it causes autistic symptoms like avoidance of eye contact, repetitive behavior and speech and language delays.
In previous studies of mice that are missing the FMR1 gene and show autistic symptoms like repetitive behavior and social avoidance, arbaclofen has been able to treat these problems. The drug works by acting on the brains GABA-B receptors and decreasing elevated activity of a neurotransmitter called glutamate; it is the absence of or problems with the FMR1 gene that causes excess glutamate in Fragile X.
In studies of mice and flies, administering arbaclofen as late as adulthood was sufficient to reverse social deficits. That finding is significant, since problems with FMR1 are likely to alter the development of the brain from birth. Whether the same effect would be found in humans is unknown, however, especially given that we undergo a longer period of brain development than do mice or flies.
Its not a cure-all, says lead author Dr. Elizabeth Berry-Kravis of Rush University Medical Center in Chicago, the lead author of the study. But this is first example of a moderately large clinical trial that took a drug that was developed on the basis of research in mice and fly models of Fragile X, and theoretically corrects the deficit at the neuronal level.
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The double-blinded six-week-long trial, which included 63 people with Fragile X ranging in age from 6 to 39, compared the effects of arbaclofen to placebo; it was originally designed to determine whether the experimental drug would reduced irritability. It was no more effective than placebo at doing that, but it did result in overall improvements in problem behaviors and social avoidance, according to the parents and caregivers of the patients.
Read more:
First Drug that Could Treat Social Withdrawal in Autism