You may have heard the exciting news about a drug being studied that shows promise in treating social withdrawal behaviors in children with Fragile-X and potentially autism. We wanted to find out more information about this drug arbaclofen (or STX209) and its effects on Fragile-X, so we sat down with Bryan King, M.D. and Director of Seattle Children’s Autism Center and Department of Child and Adolescent Psychiatry. Dr. King has been consulting with the pharmaceutical company that designed this drug and leading its trial at Seattle Children’s.

theautismblog: What is the relationship between Fragile-X Syndrome (FXS) and autism?

Dr. King: Fragile X Syndrome is a disorder associated with a specific gene defect. The product of the gene is a critical regulator of brain activity, and children with this disorder typically have significant cognitive and behavioral difficulties. In some studies, as many as 40% of individuals with FXS have an autism spectrum disorder. Since the underlying brain processes are being uncovered in FXS, and because of the overlap with autism, drugs that target FXS are of tremendous interest.

theautismblog: How was Seattle Children’s involved in this study?

Dr. King: We have been involved since the very beginning with Seaside Therapeutics, who initially came to us for advice on how to study arbaclofen when they had identified it as a drug of interest based on their work with animals. This initial study in humans is very significant from the standpoint of its proof of the concept that we can exploit our understanding of the genetic pathways that predispose to autism and related conditions. At Seattle Children’s Hospital, we were among the dozen or so sites that were able to study arbaclofen in this trial in FXS.

theautismblog: How does STX209 work?

Dr. King: In FXS, the absence of a specific protein (downstream from the genetic problem) creates a situation where the necessary balance between brain excitation and brain inhibition is disturbed. Specifically, the brakes or inhibition of certain pathways are deficient, and that leads to over-stimulation and over-excitation. It would be similar to getting a car that only had an accelerator (no brake pedal). What STX209 does is enhance the ability of a secondary pathway to try to create more balance -perhaps like strengthening the parking brake so that it might be used to slow down in the absence of a functioning brake pedal.

theautismblog: What effect did STX209 have on the participants?

Dr. King: In this study, STX209 (arbaclofen) did not have a significant effect on the behaviors that we were initially expecting to see a benefit. Specifically, we had anticipated that it would help to reduce behaviors like aggression and irritability and related behavior problems. However, and perhaps more importantly, there was a significant and positive effect seen on social withdrawal and isolation and related behaviors.

theautismblog: Did the participants experience similar results across the board or did some participants respond more than others?

Dr. King: In every clinical trial there is a range of outcomes, and some participants do very well while others do not seem to benefit -even with the same treatment. In this study, we saw some children who did very well. One, for example, seemed to experience significant improvement in his ability to use language and who as a result also improved in his ability to manage some of his frustration and behavioral outbursts.

theautismblog: How were the participants assessed?

Dr. King: The participants were assessed on a regular schedule throughout the study duration using clinical interviews, observation and rating scales.

theautismblog: It sounds like the results were very positive, with minimal side effects. What stage is this research in and how long until the FDA could approve STX209 for FSX treatment?

Dr. King: We are now participating in the next round of studies with STX209, both in FXS and also in autism. Our primary focus has shifted away from behaviors of irritability and is now directed at the areas of improvement we saw in this initial study. It could still be quite a while before the FDA approves STX209 -the preliminary results need to be replicated of course. But we are all quite optimistic about our collective experience with this drug thus far.

theautismblog: Could this become a treatment for children with autism, but not necessarily FXS?

Dr. King: It is very likely that if approval is given for the use of this drug, it will be for an indication targeting a range of behaviors in FXS (and autism) rather than specifically for FXS. But as the article highlights, this is an exciting time for research in these disorders because of the recognition that what may work in a specific subset of individuals whose autism is associated with a known genetic condition may actually have applicability for autism more broadly.

Read the research article