Pathways to New Treatments for Autism Spectrum Disorder

Two main approaches are being pursued to identify new medication treatments that may benefit children with Autism Spectrum Disorder. The first and most common approach is to evaluate a treatment in the total group of people affected by ASD, usually with a small number excluded due to the presence of a known genetic syndrome. This strategy is challenged by the lack of support for common genetic or environmental risk factors that contribute substantially to risk in the entire group of children with ASD. Therefore, treatment studies in the overall group of children with ASD are largely tied to brain systems and pathways that may modulate social function or repetitive behavior but that are not necessarily implicated in autism risk. The second approach is almost the exact opposite, to study a medication for ASD-related symptoms in a defined genetic syndrome that confers substantial risk of ASD but comprises <2% of individuals with ASD. Since animal models are providing an understanding of the underlying neurobiology that leads to autism-related symptoms in these populations, treatments targeted the root cause of these syndromes is possible. Transformative treatments, though possibly not “cures,” seem most likely to emerge from the second approach, but in a small group of children. In contrast, if the first approach is successful, we can expect a treatment that benefits a larger group of children, but likely benefits them less.  With emerging knowledge of brain systems and intersections with genetic data, we can hope for a third approach that is somewhere in the middle, with a treatment being studied in a larger subgroup of individuals with ASD that share a common biomarker. This could result from extension outward from treatments studies in rare genetic syndromes, or it could result from identification of subgroups that benefit from treatments studied in ASD as a whole. I will discuss current challenges and opportunities as we seek new treatments in autism, including specific examples of each approach.