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

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

Neurology

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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.

Original language	English (US)
Pages (from-to)	440-447
Number of pages	8
Journal	Movement Disorders Clinical Practice
Volume	7
Issue number	4
DOIs	https://doi.org/10.1002/mdc3.12940
State	Published - May 1 2020

Keywords

4RTNI
PSPRS
progressive supranuclear palsy (PSP)
salsalate
young plasma

ASJC Scopus subject areas

Neurology
Clinical Neurology

Access to Document

10.1002/mdc3.12940

Cite this

VandeVrede, L., Dale, M. L., Fields, S., Frank, M., Hare, E., Heuer, H. W., Keith, K., Koestler, M., Ljubenkov, P. A., McDermott, D., Ohanesian, N., Richards, J., Rojas, J. C., Thijssen, E. H., Walsh, C., Wang, P., Wolf, A., Quinn, J. F., Tsai, R., & Boxer, A. L. (2020). Open-Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy. Movement Disorders Clinical Practice, 7(4), 440-447. https://doi.org/10.1002/mdc3.12940

VandeVrede, L, Dale, ML, Fields, S, Frank, M, Hare, E, Heuer, HW, Keith, K, Koestler, M, Ljubenkov, PA, McDermott, D, Ohanesian, N, Richards, J, Rojas, JC, Thijssen, EH, Walsh, C, Wang, P, Wolf, A, Quinn, JF, Tsai, R & Boxer, AL 2020, 'Open-Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy', Movement Disorders Clinical Practice, vol. 7, no. 4, pp. 440-447. https://doi.org/10.1002/mdc3.12940

@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 = "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",

}

TY - JOUR

T1 - Open-Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy

AU - VandeVrede, Lawren

AU - Dale, Marian L.

AU - Fields, Scott

AU - Frank, Megan

AU - Hare, Emma

AU - Heuer, Hilary W.

AU - Keith, Kellie

AU - Koestler, Mary

AU - Ljubenkov, Peter A.

AU - McDermott, Dana

AU - Ohanesian, Noelle

AU - Richards, Jennifer

AU - Rojas, Julio C.

AU - Thijssen, Elisabeth H.

AU - Walsh, Christine

AU - Wang, Ping

AU - Wolf, Amy

AU - Quinn, Joseph F.

AU - Tsai, Richard

AU - Boxer, Adam L.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

KW - 4RTNI

KW - PSPRS

KW - progressive supranuclear palsy (PSP)

KW - salsalate

KW - young plasma

UR - http://www.scopus.com/inward/record.url?scp=85083162941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85083162941&partnerID=8YFLogxK

U2 - 10.1002/mdc3.12940

DO - 10.1002/mdc3.12940

M3 - Article

AN - SCOPUS:85083162941

SN - 2330-1619

VL - 7

SP - 440

EP - 447

JO - Movement Disorders Clinical Practice

JF - Movement Disorders Clinical Practice

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this