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

Lawren VandeVrede; Marian L Dale; Scott Fields; Megan Frank; Emma Hare; Hilary W Heuer; Kellie Keith; Mary Koestler; Peter A Ljubenkov; Dana McDermott; Noelle Ohanesian; Jennifer Richards; Julio C Rojas; Elisabeth H Thijssen; Christine Walsh; Ping Wang; Amy Wolf; Joseph F Quinn; Richard Tsai; Adam L Boxer

doi:10.1002/mdc3.12940

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

Mov Disord Clin Pract. 2020 Apr 10;7(4):440-447. doi: 10.1002/mdc3.12940. eCollection 2020 May.

Authors

Lawren VandeVrede¹, Marian L Dale², Scott Fields³, Megan Frank¹, Emma Hare¹, Hilary W Heuer¹, Kellie Keith², Mary Koestler¹, Peter A Ljubenkov¹, Dana McDermott¹, Noelle Ohanesian¹, Jennifer Richards¹, Julio C Rojas¹, Elisabeth H Thijssen^{1

4}, Christine Walsh¹, Ping Wang¹, Amy Wolf¹, Joseph F Quinn², Richard Tsai¹, Adam L Boxer¹

Affiliations

¹ Memory and Aging Center, Department of Neurology University of California San Francisco California USA.
² OHSU Parkinson Center and Movement Disorder Program, Department of Neurology Oregon Health and Science University Portland, Oregon USA.
³ Department of Pharmaceutical Services University of California San Francisco California USA.
⁴ Neurochemistry Laboratory, Department of Clinical Chemistry VU University Medical Center Amsterdam The Netherlands.

Abstract

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 (cm³ ± 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.

Keywords: 4RTNI; PSPRS; progressive supranuclear palsy (PSP); salsalate; young plasma.

Abstract

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