A53T-specific ASO

A53T-specific ASO is an allele-specific antisense oligonucleotide (ASO) being developed by Vanda Pharmaceuticals for the treatment of Parkinson's disease (PD). It is an 18-mer gapmer featuring phosphorothioate (PS) and methoxyethyl (MOE) modifications, designed to selectively target the p.A53T missense mutation in the SNCA gene. This mutation, first identified by Dr. Polymeropoulos, leads to the production of a pathogenic form of α-synuclein that drives early-onset autosomal dominant PD. Unlike broad SNCA-targeting ASOs that may deplete the essential wild-type α-synuclein pool, this candidate achieves genotype-selective downregulation of the mutant allele while preserving the expression and function of the wild-type protein. Preclinical data in HEL cells and patient-derived induced pluripotent stem cell (iPSC) neuronal models have demonstrated significant reduction in SNCA expression and potential for rescuing PD-relevant phenotypes.

Other names

allele-specific ASO targeting p.A53T SNCAp.A53T SNCA ASO