Mass General - Division of Clinical Research

• Male or female participants aged 50 to 80 years, inclusive, at the time of informed consent. - Diagnosis of possible or probable PSP of the Richardson's Syndrome (PSP-RS) phenotypes according to the Movement Disorders Society's Progressive Supranuclear Palsy (MDS PSP) clinical features criteria. At least 1 (either 1 or both) of the following 2 items must be met: 1. Vertical supranuclear gaze palsy. 2. Slowing of vertical saccades AND postural instability with falls within the first 3 years of PSP symptoms. - Presence of PSP symptoms ≤3 years. - MoCA score ≥23 - Full 28-item PSPRS score ≤40. - Able to ambulate independently or with minimal assistance defined as the ability to take at least 10 steps (stabilization of 1 arm [ie, use of cane]). - Body weight range ≥43 kg/95 lbs to ≤120 kg/265 lbs. - Reside outside a skilled nursing facility or dementia care facility. - Has a caregiver or study partner who will accompany them to the study visits. The caregiver or study partner must be a person who has frequent contact (at least 7 hours per week at 1 time or in different days) with the participant and is able to provide information about the participant's medication and overall condition. Prior to the conduct of any study procedures, the caregiver or study partner must be willing to sign the independent ethics committee (IEC)/institutional review board (IRB) approved informed consent.

Non-PSP- RS Movement Disorders or other central nervous system (CNS) Diseases - Score of 3 on any functional domain in the PSP-CDS. - Participants with known genetic mutation (based on familiar or clinical history). - Evidence of other neurological disorder that could explain signs of PSP (eg, Parkinson's disease, Alzheimer disease, etc.). - Brain magnetic resonance imaging (MRI) within 1 year of screening consistent with: - Primary degenerative diseases other than PSP. Procedures - For the optional substudy only: Contraindication or refusal to undergo 2 lumbar punctures for obtaining CSF. - Contraindication or inability to tolerate MRI for volumetric brain MRI assessments throughout the study.