Journal
MOVEMENT DISORDERS
Volume 30, Issue 11, Pages 1442-1450Publisher
WILEY
DOI: 10.1002/mds.26354
Keywords
autophagy; gene therapy; LRRK2; mitochondria; neuroprotection
Categories
Funding
- Michael J. Fox Foundation for Parkinson's Research
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Parkinson's UK
- Parkinson Society Canada
- Canadian Health Institutes of Research (CIHR)
- Brain Canada
- Canadian Institutes of Health Research
- Edmond J. Safra Philanthropic Foundation
- Michael J. Fox Foundation
- National Parkinson Foundation
- Tourette Syndrome Association
- W. Garfield Weston Foundation
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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 alpha-synuclein (alpha-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. (c) 2015 International Parkinson and Movement Disorder Society
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