Movement Disorders

Volume 30, Issue 11 p. 1442-1450

Review

Disease-modifying strategies for Parkinson's disease

Lorraine V. Kalia MD, PhD,

Lorraine V. Kalia MD, PhD

Division of Neurology, Department of Medicine, Toronto Western Hospital, University of Toronto, Canada

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada

Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital

Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

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Suneil K. Kalia MD, PhD,

Suneil K. Kalia MD, PhD

Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Canada

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Anthony E. Lang MD,

Corresponding Author

Anthony E. Lang MD

Division of Neurology, Department of Medicine, Toronto Western Hospital, University of Toronto, Canada

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada

Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital

Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

Correspondence to: Dr. Anthony Lang, Movement Disorders Clinic, Toronto Western Hospital, 399 Bathurst Street, McL 7, Toronto, Ontario, M5T 2S8, Canada, E-mail: [email protected]Search for more papers by this author

Lorraine V. Kalia MD, PhD,

Lorraine V. Kalia MD, PhD

Division of Neurology, Department of Medicine, Toronto Western Hospital, University of Toronto, Canada

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada

Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital

Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

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Suneil K. Kalia MD, PhD,

Suneil K. Kalia MD, PhD

Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Canada

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Anthony E. Lang MD,

Corresponding Author

Anthony E. Lang MD

Division of Neurology, Department of Medicine, Toronto Western Hospital, University of Toronto, Canada

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada

Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital

Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

First published: 24 July 2015

https://doi.org/10.1002/mds.26354

Citations: 176

Funding agencies: L.V.K. holds a Canadian Health Institutes of Research (CIHR) Clinician-Scientist Award and receives research support from Michael J. Fox Foundation for Parkinson's Research, Natural Sciences and Engineering Research Council of Canada (NSERC), and Parkinson's UK. S.K.K. receives research support from Michael J. Fox Foundation for Parkinson's Research and Parkinson Society Canada. A.E.L. holds the Jack Clark Chair in Parkinson's Disease Research at the University of Toronto and the Lily Safra Chair in Movement Disorders at the University Health Network, Toronto, Canada and received grants from Brain Canada, Canadian Institutes of Health Research, Edmond J. Safra Philanthropic Foundation, Michael J. Fox Foundation, National Parkinson Foundation, Parkinson Society Canada, Tourette Syndrome Association, and W. Garfield Weston Foundation.

Relevant conflicts of interest/financial disclosures: Nothing to report.

Full financial disclosures and author roles may be found in the online version of this article.

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Abstract

Parkinson's disease (PD) is an increasingly prevalent and progressively disabling neurodegenerative disease. The impact of PD on patients and their families as well as its burden on health care systems could be substantially reduced by disease-modifying therapies that slow the rate of neurodegeneration or stop the disease process. Multiple agents have been studied in clinical trials designed to assess disease modification in PD, but all have failed. Over the last 3 years, clinical trials investigating the potential of adeno-associated virus serotype 2 (AAV)-neuturin, coenzyme Q10, creatine, pramipexole, and pioglitazone reported negative findings or futility. Despite these disappointments, progress has been made by expanding our understanding of molecular pathways involved in PD to reveal new targets, and by developing novel animal models of PD for preclinical studies. Currently, at least eight ongoing clinical trials are testing the promise of isradipine, caffeine, nicotine, glutathione, AAV2-glial cell-line derived neurotrophic factor (GDNF), as well as active and passive immunization against α-synuclein (α-Syn). In this review, we summarize the clinical trials of disease-modifying therapies for PD that were published since 2013 as well as clinical trials currently in progress. We also discuss promising approaches and ongoing challenges in this area of PD research. © 2015 International Parkinson and Movement Disorder Society

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Volume30, Issue11

Special Issue:New Treatments in Parkinson Disease and Movement Disorders

15 September 2015

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