Current Perspectives in Autism Spectrum Disorder: From Genes to Therapy

Abstract

Autism spectrum disorder (ASD) is a constellation of neurodevelopmental presentations with high heritability and both phenotypic and genetic heterogeneity. To date, mutations in hundreds of genes have been associated to varying degrees with increased ASD risk. A better understanding of the functions of these genes and whether they fit together in functional groups or impact similar neuronal circuits is needed to develop rational treatment strategies. We will review current areas of emphasis in ASD research, starting from human genetics and exploring how mouse models of human mutations have helped identify specific molecular pathways (protein synthesis and degradation, chromatin remodeling, intracellular signaling), which are linked to alterations in circuit function and cognitive/social behavior. We will conclude by discussing how we can leverage the findings on molecular and cellular alterations found in ASD to develop therapies for neurodevelopmental disorders.

Keywords: animal models; autism spectrum disorder; genetics; therapeutics.

Figure 1.

The complex path from gene identification to therapy development in ASD. Although the ideal path from gene identification to therapy development via animal models appears linear (A), genetic and phenotypic heterogeneity prevents therapeutic advances in ASD and other complex disorders. Possible therapies will need to be customized based on the specific underlying molecular changes for subcategories that are still in the process of being defined (B). Combination approaches (e.g., multiple compounds targeting different mechanisms or endophenotypes) may also be necessary.