Targeted therapies for fragile X syndrome: current state and future direction of clinical trials in humans

Author(s): Christoph Kamm

Fragile X syndrome (FXS) is the most common monogenetic and testable cause of intellectual disability and autism spectrum disorders. FXS is caused by a ‘full mutation’ (>200 CGG repeats) in the FMR1 gene. The phenotypic features of FXS are highly variable, frequently include autistic features or other behavioral abnormalities, and may comprise a distinctive appearance. In recent years, considerable progress has been reached in our understanding of the molecular pathophysiology and the impairment of neurobiological processes underlying the manifestation of FXS, to a large extent derived from work on animal models, especially on FMR1- knockout mice. These discoveries have led to the initiation of clinical trials with novel targeted drug treatments in humans with FXS. This review provides an overview of selected promising therapeutic targets and the current state of these clinical trials.