SNCA p.A53T allele-specific antisense oligonucleotide

SNCA p.A53T allele-specific antisense oligonucleotide is an allele-specific antisense oligonucleotide (ASO) being developed by Vanda Pharmaceuticals in collaboration with the Hellenic Pasteur Institute for the treatment of Parkinson's disease [VIRTUAL-230]. It is designed as an 18-mer gapmer featuring phosphorothioate (PS) and methoxyethyl (MOE) modifications that selectively target the mutant p.A53T allele of the alpha-synuclein (SNCA) gene. This mutation is a significant risk factor for early-onset autosomal-dominant Parkinson's disease [VIRTUAL-230]. Unlike broad SNCA-targeting therapies that risk depleting essential wild-type alpha-synuclein, this genotype-selective approach achieves selective downregulation of the pathogenic mutant allele while preserving wild-type expression and function. In preclinical studies, including patient-derived induced pluripotent stem cell (iPSC) neuronal models, treatment with this ASO significantly reduced SNCA expression, diminished phosphorylated alpha-synuclein, restored neurite branching, and improved synaptic connectivity [VIRTUAL-230].

Other names

A53T-specific ASOA-53T-specific ASOA 53T-specific ASOSNCA A53T ASO