In preclinical studies, significant and dose-dependent reductions of mHTT and improvement in motor function were observed in vivo in the disease mouse models of HD [68] and also in vitro in HD patient cell models.[70,71] The Phase 1/2a clinical trial of VO659 is a multi-center, open-label basket study designed to assess the safety and tolerability of multiple ascending doses of VO659 administered intrathecally in participants with early manifest HD or mild to moderate SCA1 or SCA3 (NCT05822908). Here, ATXN3 is linked to Huntington disease.