Friday, April 8, 2016

New CHOP Research Study Tests Brain’s Response to Single Dose of Arbaclofen (STX209)

Many in the autism community are familiar with the trial drug STX209, also called arbaclofen, which affects a chemical system called GABA. In 2010, clinical trials were launched to evaluate whether arbaclofen might become the first medication to treat core symptoms of social communication impairment and repetitive behavior in autism spectrum disorder (ASD).

Among a small subset of participants in these early clinical trials, the drug showed promise for treating secondary outcomes- namely, some of the social symptoms that accompany autism spectrum disorder (ASD) and fragile X syndrome (FXS).

In order to declare a medication trial a success, drug developers need to be able to predict what the drug will do and then show that it performs as promised. While a small set of patients did see improvements- particularly in the area of social withdrawal- researchers weren’t able to predict which children would see positive treatment effects or what those positive effects would be. This is a common challenge in studying ASD, since symptoms can vary so widely in their expression. As a result, in 2013, the drug’s manufacturer discontinued a clinical trial of the drug, citing a lack of funding and unproven efficacy for the drug’s primary outcomes in treating ASD and FSX.

For the families whose children did display social and behavioral improvements during the drug trial, it was disappointing to receive the news that the study was discontinued and that the manufacturer could no longer afford to keep manufacturing the drug.

Researchers remain interested in finding ways to test the effects of the very limited quantities of arbaclofen that remain. To that end, CHOP was recently approved to conduct a brain imaging study that will use magnetoencephalography (MEG) and magnetic resonance Imaging (MRI) to determine whether a single dose of Arbaclofen results in any changes in brain activity in boys aged 14-17 with ASD. Whereas the initial studies just looked at behavioral outcomes, the CHOP research team is trying to explore the brain’s response to the drug. Funding for the new study comes from Clinical Research Associates, a subsidiary of the Simons Foundation.

“The study will allow us to look at a very specific mechanism of STX209,” said the study’s lead investigator, Timothy Roberts, PhD, Oberkircher Family Chair in Pediatric Radiology at The Children's Hospital of Philadelphia. “By testing the effects of the drug in single doses, we will be able to determine if it does indeed have a fast effect on changing brain activity, and if those changes in brain activity depend on the dose of the medication.” Roberts followed up; “Moreover, by examining the intricacies of brain activity with MEG before administering each dose, we hope to find biologically-based signs that predict whose brain might respond and whose might not, and thus provide a stratification basis for inclusion in any future trials.”

Incremental findings like this could help the scientific community determine whether there is a case for resuming clinical trials focused on arbaclofen.

More information about the study and how to participate is available here.

For more about the history of the arbaclofen trials and recent studies of the drug in animal models, check out this podcast from the Autism Science Foundation.