Twelve Years of Drug Prioritization to Help Accelerate Disease Modification Trials in Parkinson's Disease: The International Linked Clinical Trials Initiative

Richard K Wyse¹, Tom Isaacs¹, Roger A Barker², Mark R Cookson³, Ted M Dawson⁴, David Devos⁵, David T Dexter⁶, Joy Duffen¹, Howard Federoff⁷, Brian Fiske⁸, Thomas Foltynie⁹, Susan Fox¹⁰, J Timothy Greenamyre¹¹, Karl Kieburtz¹², Jeffrey H Kordower¹³, Dimitri Krainc¹⁴, Helen Matthews¹, Darren J Moore¹⁵, Leah Mursaleen¹, Michael A Schwarzschild¹⁶, Simon R W Stott¹, David Sulzer¹⁷, Per Svenningsson¹⁸, Caroline M Tanner¹⁹, Camille Carroll²⁰, David K Simon²¹, Patrik Brundin²²

Affiliations

¹ Cure Parkinson's, London, UK.
² Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
³ Cell Biology and Gene Expression Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁴ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Medical Pharmacology and Neurology, University of Lille, CHU Lille, Lille Neurosciences and Cognition Inserm UMR-S-U1172, Lille, France.
⁶ Parkinson's UK, London, UK.
⁷ Henry and Susan Samueli College of Health Sciences, University of California, Irvine CA, USA.
⁸ Research Programs, The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
⁹ Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
¹⁰ Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Neurology, Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
¹² Department of Neurology Center for Health and Technology, University of Rochester, Rochester, NY, USA.
¹³ ASU-Banner Neurodegenerative Disease Research Center and School of Life Sciences, Arizona State University, Tempe, AZ, USA.
¹⁴ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁵ Van Andel Institute, Grand Rapids, MI, USA.
¹⁶ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
¹⁷ Department of Neurology, Columbia University, New York, NY, USA.
¹⁸ Karolinska Institute, Stockholm, Sweden.
¹⁹ Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁰ Translational and Clinical Research Institute, Newcastle University, Newcastle, UK.
²¹ Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
²² Neuroscience and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland.

PMID: 38578902
PMCID: PMC11191436
DOI: 10.3233/JPD-230363

Review

Twelve Years of Drug Prioritization to Help Accelerate Disease Modification Trials in Parkinson's Disease: The International Linked Clinical Trials Initiative

Richard K Wyse et al. J Parkinsons Dis. 2024.

. 2024;14(4):657-666.

doi: 10.3233/JPD-230363.

Authors

Affiliations

¹ Cure Parkinson's, London, UK.
² Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
³ Cell Biology and Gene Expression Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁴ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Medical Pharmacology and Neurology, University of Lille, CHU Lille, Lille Neurosciences and Cognition Inserm UMR-S-U1172, Lille, France.
⁶ Parkinson's UK, London, UK.
⁷ Henry and Susan Samueli College of Health Sciences, University of California, Irvine CA, USA.
⁸ Research Programs, The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
⁹ Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
¹⁰ Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Neurology, Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
¹² Department of Neurology Center for Health and Technology, University of Rochester, Rochester, NY, USA.
¹³ ASU-Banner Neurodegenerative Disease Research Center and School of Life Sciences, Arizona State University, Tempe, AZ, USA.
¹⁴ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁵ Van Andel Institute, Grand Rapids, MI, USA.
¹⁶ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
¹⁷ Department of Neurology, Columbia University, New York, NY, USA.
¹⁸ Karolinska Institute, Stockholm, Sweden.
¹⁹ Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁰ Translational and Clinical Research Institute, Newcastle University, Newcastle, UK.
²¹ Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
²² Neuroscience and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland.

PMID: 38578902
PMCID: PMC11191436
DOI: 10.3233/JPD-230363

Abstract

In 2011, the UK medical research charity Cure Parkinson's set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson's disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.

Keywords: Clinical trials; Parkinson’s disease; disease modification; drug repurposing; neuroprotection.

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Conflict of interest statement

Patrik Brundin, Roger Barker, Camille Carroll, Mark Cookson, Jeffrey Kordower, Ted Dawson, Howard Federoff, Tom Foltynie, Timothy Greenamyre, Dimitri Krainc, Darren Moore, David L Sulzer, and Caroline Tanner are all Editorial Board Members of this journal, but were not involved in the peer-review process nor had access to any information regarding its peer-review.

References

1. Bloem BR, Okun MS, Klein C (2021) Parkinson’s disease. Lancet 397, 2284–2303. - PubMed
1. GBD 2016 Parkinson’s Disease Collaborators (2018) 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, 939–953. - PMC - PubMed
1. Ray Dorsey E, Elbaz A, Nichols E, Abd-Allah F, Abdelalim A, Adsuar JC, Ansha MG, Brayne C, Choi JYJ, Collado-Mateo D, Dahodwala N, Do HP, Edessa D, Endres M, Fereshtehnejad SM, Foreman KJ, Gankpe FG, Gupta R, Hankey GJ, Hay SI, Hegazy MI, Hibstu DT, Kasaeian A, Khader Y, Khalil I, Khang YH, Kim YJ, Kokubo Y, Logroscino G, Massano J, Ibrahim NM, Mohammed MA, Mohammadi A, Moradi-Lakeh M, Naghavi M, Nguyen BT, Nirayo YL, Ogbo FA, Owolabi MO, Pereira DM, Postma MJ, Qorbani M, Rahman MA, Roba KT, Safari H, Safiri S, Satpathy M, Sawhney M, Shafieesabet A, Shiferaw MS, Smith M, Szoeke CEI, Tabarés-Seisdedos R, Truong NT, Ukwaja KN, Venketasubramanian N, Villafaina S, Weldegwergs KG, Westerman R, Wijeratne T, Winkler AS, Xuan BT, Yonemoto N, Feigin VL, Vos T, Murray CJL (2018) 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, 939–953. - PMC - PubMed
1. Savica R, Grossardt BR, Bower JH, Eric Ahlskog J, Rocca WA (2016) Time trends in the incidence of Parkinson disease. JAMA Neurol 73, 981–989. - PMC - PubMed
1. World Health Organization (2022) Parkinson disease: A public health approach. World Health Organization. https://www.who.int/publications/i/item/9789240050983.

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Twelve Years of Drug Prioritization to Help Accelerate Disease Modification Trials in Parkinson's Disease: The International Linked Clinical Trials Initiative

Affiliations

Twelve Years of Drug Prioritization to Help Accelerate Disease Modification Trials in Parkinson's Disease: The International Linked Clinical Trials Initiative

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Full Text Sources

Medical

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