Seeking progress in disease modification in Parkinson disease

Codrin Lungu¹, Jesse M Cedarbaum², Ted M Dawson³, E Ray Dorsey⁴, Carlos Faraco⁵, Howard J Federoff⁶, Brian Fiske⁷, Robert Fox⁸, Andrew M Goldfine⁹, Karl Kieburtz⁴, Eric A Macklin¹⁰, Helen Matthews¹¹, Gary Rafaloff¹², Rachel Saunders-Pullman¹³, Nina F Schor¹⁴, Michael A Schwarzschild¹⁰, Beth-Anne Sieber¹⁵, Tanya Simuni¹⁶, Dalton J Surmeier¹⁶, Amir Tamiz¹⁷, Milton H Werner¹⁸, Clinton B Wright⁵, Richard Wyse¹¹

Affiliations

¹ Division of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 6001 Executive Blvd, #2188, Rockville, MD, 20852, USA. Electronic address: lunguci@ninds.nih.gov.
² Coeruleus Clinical Sciences LLC, Woodbridge, CT, USA.
³ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ University of Rochester Medical Center, Rochester, NY, USA.
⁵ Division of Clinical Research, NINDS, NIH, Bethesda, MD, USA.
⁶ University of California, Irvine, Irvine, CA, USA.
⁷ The Michael J Fox Foundation for Parkinson's Research, New York, NY, USA.
⁸ Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ GlaxoSmithKline, Upper Providence, PA, USA.
¹⁰ Massachusetts General Hospital, Boston, MA, USA.
¹¹ The Cure Parkinson's Trust, London, UK.
¹² Patient Research Advocate, New York, NY, USA.
¹³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ NINDS, NIH, Bethesda, MD, USA.
¹⁵ Division of Neuroscience, NINDS, NIH, Bethesda, MD, USA.
¹⁶ Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁷ Division of Translational Research, NINDS, NIH, Bethesda, MD, USA.
¹⁸ Inhibikase Therapeutics, Inc, Atlanta, GA, USA.

PMID: 34561166
PMCID: PMC11770554
DOI: 10.1016/j.parkreldis.2021.09.006

Review

Seeking progress in disease modification in Parkinson disease

Codrin Lungu et al. Parkinsonism Relat Disord. 2021 Sep.

. 2021 Sep:90:134-141.

doi: 10.1016/j.parkreldis.2021.09.006. Epub 2021 Sep 10.

Authors

Affiliations

¹ Division of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 6001 Executive Blvd, #2188, Rockville, MD, 20852, USA. Electronic address: lunguci@ninds.nih.gov.
² Coeruleus Clinical Sciences LLC, Woodbridge, CT, USA.
³ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ University of Rochester Medical Center, Rochester, NY, USA.
⁵ Division of Clinical Research, NINDS, NIH, Bethesda, MD, USA.
⁶ University of California, Irvine, Irvine, CA, USA.
⁷ The Michael J Fox Foundation for Parkinson's Research, New York, NY, USA.
⁸ Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ GlaxoSmithKline, Upper Providence, PA, USA.
¹⁰ Massachusetts General Hospital, Boston, MA, USA.
¹¹ The Cure Parkinson's Trust, London, UK.
¹² Patient Research Advocate, New York, NY, USA.
¹³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ NINDS, NIH, Bethesda, MD, USA.
¹⁵ Division of Neuroscience, NINDS, NIH, Bethesda, MD, USA.
¹⁶ Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁷ Division of Translational Research, NINDS, NIH, Bethesda, MD, USA.
¹⁸ Inhibikase Therapeutics, Inc, Atlanta, GA, USA.

PMID: 34561166
PMCID: PMC11770554
DOI: 10.1016/j.parkreldis.2021.09.006

Abstract

Objective: Disease modification in Parkinson disease (PD) has remained an elusive goal, in spite of large investments over several decades. Following a large meeting of experts, this review article discusses the state of the science, possible reasons for past PD trials' failures to demonstrate disease-modifying benefit, and potential solutions.

Methods: The National Institute of Neurological Disorders and Stroke (NINDS) convened a meeting including leaders in the field and representatives of key stakeholder groups to discuss drug therapy with the goal of disease modification in PD.

Results: Important lessons can be learned from previous attempts, as well as from other fields. The selection process for therapeutic targets and agents differs among various organizations committed to therapeutic development. The areas identified as critical to target in future research include the development of relevant biomarkers, refinements of the targeted patient populations, considerations of novel trial designs, and improving collaborations between all stakeholders.

Conclusions: We identify potential barriers to progress in disease modification for Parkinson's and propose a set of research priorities that may improve the likelihood of success.

Keywords: Clinical trial; Disease modification; Parkinson; Pharmacotherapy.

Published by Elsevier Ltd.

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Figures

**Fig. 1.**
Biomarker types and staged applications.

**Fig. 2.**
Collaboration model for PD drug development.

See this image and copyright information in PMC

References

1. Collaborators GBDPsD, Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016, Lancet Neurol. 17 (11) (2018. Nov) 939–953. - PMC - PubMed
1. Olanow CW, Wunderle KB, Kieburtz K, Milestones in movement disorders clinical trials: advances and landmark studies, Mov. Disord. 26 (6) (2011. May) 1003–1014. - PubMed
1. Simuni T, Fiske B, Merchant K, et al., Nilotinib IN patients with advanced parkinsons disease: a randomized phase 2A study (NILO-PD), JAMA Neurol. 78 (3) (2021) 312–320, 10.1001/jamaneurol.2020.4725. - DOI - PMC - PubMed
1. Pagan FL, Hebron ML, Wilmarth B, et al., Nilotinib effects on safety, tolerability, and potential biomarkers in Parkinson disease: a phase 2 randomized clinical trial, JAMA neurology 77 (3) (2020. Mar 1) 309–317. - PMC - PubMed
1. Parkinson Study Group S-PDIIII, Isradipine versus placebo in early Parkinson disease: a randomized trial, Ann. Intern. Med. 172 (9) (2020. May 5) 591–598. - PMC - PubMed

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Seeking progress in disease modification in Parkinson disease

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Seeking progress in disease modification in Parkinson disease

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