Open-Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy

Background Progressive supranuclear palsy (PSP) is a neurodegenerative disease without approved therapies, and therapeutics are often tried off-label in the hope of slowing disease progression. Results from these experiences are seldom shared, which limits evidence-based knowledge to guide future treatment decisions. Objectives To describe an open-label experience, including safety/tolerability, and longitudinal changes in biomarkers of disease progression in PSP-Richardson's syndrome (PSP-RS) patients treated with either salsalate or young plasma and compare to natural history data from previous multicenter studies. Methods For 6 months, 10 PSP-RS patients received daily salsalate 2,250 mg, and 5 patients received monthly infusions of four units of young plasma. Every 3 months, clinical severity was assessed with the Progressive Supranuclear Palsy Rating Scale (PSPRS), and MRI was obtained for volumetric measurement of midbrain. A range of exploratory biomarkers, including cerebrospinal fluid levels of neurofilament light chain, were collected at baseline and 6 months. Interventional data were compared to historical PSP-RS patients from the davunetide clinical trial and the 4-Repeat Tauopathy Neuroimaging Initiative. Results Salsalate and young plasma were safe and well tolerated. PSPRS change from baseline (mean +/- standard deviation [SD]) was similar in salsalate (+5.6 +/- 9.6), young plasma (+5.0 +/- 7.1), and historical controls (+5.6 +/- 7.1), and change in midbrain volume (cm(3) +/- SD) did not differ between salsalate (-0.07 +/- 0.03), young plasma (-0.06 +/- 0.03), and historical controls (-0.06 +/- 0.04). No differences were observed between groups on any exploratory endpoint. Conclusions Neither salsalate nor young plasma had a detectable effect on disease progression in PSP-RS. Focused open-label clinical trials incorporating historical clinical, neuropsychological, fluid, and imaging biomarkers provide useful preliminary data about the promise of novel PSP-directed therapies.