Adult participants with spinocerebellar ataxia type 2 (SCA2) who carry ≥33 cytosine, adenine, guanine (CAG) repeats in the ATXN2 gene, and who have met all protocol eligibility criteria will be randomized to receive a single dose of ARO-ATXN2 or placebo and be evaluated for safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters.

Inclusion Criteria:

• Non-pregnant, non-lactating
• Diagnosis of symptomatic SCA2 and ≥33 CAG repeats in the ATXN2 gene based on source verifiable medical records or genetic testing at Screening
• Scale of Assessment and Rating of Ataxia (SARA) score ≤14
• Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later

Exclusion Criteria:

• Uncontrolled hypertension (blood pressure >160/100 mmHg)
• History of having received stem cell therapy
• Clinically significant cardiac, liver, or renal disease
• Human immunodeficiency virus (HIV) infection (seropositive at Screening)
• Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening
• Intellectual disability or significant behavioral neuropsychiatric manifestation
• Any contraindications to lumbar puncture, including INR >1.4, platelet count <100,000, and use of anticoagulant or antiplatelet medications that cannot be safely interrupted
• Presence of an implanted shunt for drainage of CSF or an implanted central nervous system (CNS) catheter

Note: Additional inclusion/exclusion criteria may apply per protocol.