@article{fd57fd1487de4b308f34490c7634e116,
title = "Open-Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy",
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",
author = "Lawren VandeVrede and Dale, {Marian L.} and Scott Fields and Megan Frank and Emma Hare and Heuer, {Hilary W.} and Kellie Keith and Mary Koestler and Ljubenkov, {Peter A.} and Dana McDermott and Noelle Ohanesian and Jennifer Richards and Rojas, {Julio C.} and Thijssen, {Elisabeth H.} and Christine Walsh and Ping Wang and Amy Wolf and Quinn, {Joseph F.} and Richard Tsai and Boxer, {Adam L.}",
note = "Funding Information: L.V. has received travel support from the Tau Consortium and salary support through a 5T32AG023481 grant. M.L.D. receives medical loan repayment support through the NIH‐NINDS Loan Repayment Program. J.C.R. received funds from the NIH (K23AG059888) and is a site investigator for clinical programs sponsored by Eli‐Lilly. J.F.Q. is reimbursed for DSMB service by VTV Pharmaceuticals and Retrophin. R.T. has received research support from the NIH (K23AG055688) and University of California; has served as a consultant for Grifols, ExpertConnect, and Barclays; and currently works as Associate Medical Director at Denali Therapeutics. A.L.B. receives research support from the NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association. He has served as a consultant for Aeton, AbbVie, Alector, Amgen, Arkuda, Arvinas, Asceneuron, Ionis, Lundbeck, Novartis, Passage BIO, Samumed, Third Rock, Toyama, and UCB and received research support from Avid, Biogen, BMS, C2N, Cortice, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche, and TauRx. Financial Disclosures for previous 12 months: Funding Information: The study was funded by the Tau Consortium and by NIH grant 2R01AG038791. J.C.R. received funds from the NIH and is a site investigator for clinical programs sponsored by Eli‐Lilly. J.F.Q. is reimbursed for DSMB service by VTV Pharmaceuticals and Retrophin. R.T. received research funds from the NIH; has served as a consultant for Grifols, ExpertConnect, and Barclays; and is currently an employee of Denali Therapeutics. A.L.B. received research support from the NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association. He has served as a consultant for Aeton, AbbVie, Alector, Amgen, Arkuda, Arvinas, Asceneuron, Ionis, Lundbeck, Novartis, Passage BIO, Samumed, Third Rock, Toyama, and UCB and received research support from Avid, Biogen, BMS, C2N, Cortice, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche, and TauRx. Financial Sources and Conflicts of Interest: Funding Information: Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Institutional review board approval was obtained at both USCF and OHSU sites. Written informed consent was obtained from all patients and their caregivers. Financial Sources and Conflicts of Interest: The study was funded by the Tau Consortium and by NIH grant 2R01AG038791. J.C.R. received funds from the NIH and is a site investigator for clinical programs sponsored by Eli-Lilly. J.F.Q. is reimbursed for DSMB service by VTV Pharmaceuticals and Retrophin. R.T. received research funds from the NIH; has served as a consultant for Grifols, ExpertConnect, and Barclays; and is currently an employee of Denali Therapeutics. A.L.B. received research support from the NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association. He has served as a consultant for Aeton, AbbVie, Alector, Amgen, Arkuda, Arvinas, Asceneuron, Ionis, Lundbeck, Novartis, Passage BIO, Samumed, Third Rock, Toyama, and UCB and received research support from Avid, Biogen, BMS, C2N, Cortice, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche, and TauRx. Financial Disclosures for previous 12 months: L.V. has received travel support from the Tau Consortium and salary support through a 5T32AG023481 grant. M.L.D. receives medical loan repayment support through the NIH-NINDS Loan Repayment Program. J.C.R. received funds from the NIH (K23AG059888) and is a site investigator for clinical programs sponsored by Eli-Lilly. J.F.Q. is reimbursed for DSMB service by VTV Pharmaceuticals and Retrophin. R.T. has received research support from the NIH (K23AG055688) and University of California; has served as a consultant for Grifols, ExpertConnect, and Barclays; and currently works as Associate Medical Director at Denali Therapeutics. A.L.B. receives research support from the NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association. He has served as a consultant for Aeton, AbbVie, Alector, Amgen, Arkuda, Arvinas, Asceneuron, Ionis, Lundbeck, Novartis, Passage BIO, Samumed, Third Rock, Toyama, and UCB and received research support from Avid, Biogen, BMS, C2N, Cortice, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche, and TauRx. Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",
year = "2020",
month = may,
day = "1",
doi = "10.1002/mdc3.12940",
language = "English (US)",
volume = "7",
pages = "440--447",
journal = "Movement Disorders Clinical Practice",
issn = "2330-1619",
publisher = "John Wiley and Sons Ltd",
number = "4",
}