The landmark approval by the FDA of the orally administered splicing modifier Evrysdi™ (risdiplam) for the treatment of SMA, ushered in a new era of thinking around the use of splicing modulation for the treatment of unmet medical needs. PTC Therapeutics has developed technologies to uncover splicing modifiers for additional applications, including the treatment of Huntington’s Disease. Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by expansion of CAG trinucleotide repeats in the HTT gene. Consequently, the mutant protein is ubiquitously expressed and drives pathogenesis of HD through a toxic gain-of-function mechanism. We have identified small molecules that lower <i>HTT</i> expression by promoting the inclusion of a pseudoexon that contains a premature termination codon. The resulting mRNA is rapidly degraded leading to a reduction in HTT protein levels.

Landscape beyond SMA: Expanding splicing modulation for the treatment of genetic disorders

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.