TS1-ASO

TS1-ASO is an antisense oligonucleotide (ASO) designed to treat Timothy Syndrome Type 1 (TS1), a rare and severe multisystem disorder caused by a specific gain-of-function mutation (G406R) in exon 8A of the *CACNA1C* gene. This mutation results in the failure of the Cav1.2 calcium channel to inactivate properly, leading to excessive calcium influx and subsequent cardiac arrhythmias, autism, and other neurodevelopmental issues. TS1-ASO targets the *CACNA1C* pre-mRNA to modulate splicing, specifically suppressing the inclusion of the mutant exon 8A and promoting the inclusion of the alternative, wild-type exon 8. By shifting the splicing pattern, the therapy aims to restore normal calcium channel function and alleviate neuropsychiatric symptoms. It is currently being evaluated in a Phase I/II clinical trial sponsored by Stanford University for intrathecal administration in pediatric patients.