hASO2

hASO2 is an antisense oligonucleotide (ASO) designed to target and reduce the expression of the human *SNCA* gene, which encodes the α-synuclein (aSyn) protein. Developed by Ionis Pharmaceuticals in collaboration with Biogen, hASO2 functions as a RNase H-dependent gapmer that binds to *SNCA* mRNA, leading to its degradation and a subsequent decrease in α-synuclein protein levels. This approach aims to address the underlying pathology of Parkinson's disease and other synucleinopathies, where the accumulation of α-synuclein aggregates is a hallmark. Preclinical studies in rodent and non-human primate models have demonstrated that hASO2 can reduce established α-synuclein pathology and prevent dopaminergic dysfunction. The clinical candidate corresponding to hASO2, known as BIIB094 (ION-822), was evaluated in Phase 1 trials but was discontinued in early 2024.

Other names

SNCA ASOalpha-synuclein antisense oligonucleotide