This is a Phase 2, double-blind, placebo-controlled, multi-center, Phase II, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and efficacy of Ya-101 in subjects with multiple system atrophy.

The purpose of the study is to evaluate 2 doses of YA-101 compared to placebo in MSA patients, including: 1) safety and tolerability, 2) pharmacokinetics, and 3) potential efficacy of YA-101.

Inclusion Criteria:

1. Able to understand the process of the clinical trial and give informed consent for the participation of the study.
2. Diagnosis of MSA according to MDS clinical criteria (Wenning et al, 2022), including subjects with MSA of either subtype (MSA-P or MSA-C).
3. Males or non-pregnant, non-lactating females with no child-bearing potential, or agree to use 2 forms of contraception.
4. Able to take oral medications.
5. Able to ambulate without the assistance of another person.

Exclusion Criteria:

1. Positive urine test for drugs of abuse and/or alcohol test both at screening and Day 1.
2. Evidence of renal impairment or hepatic impairment.
3. Subject with a Mini-Mental State Examination (MMSE) score of 24 or lower.
4. Medical history includes severe systemic diseases such as cardiopulmonary failure, severe liver or kidney disease, and uncontrolled diabetes; significant central nervous system disorders like stroke, encephalitis, and epilepsy and severe head trauma; peptic ulcer in one year prior to screening.
5. Positive results for active viral infections, including human immunodeficiency virus (HIV), hepatitis B, and hepatitis C.