title: Disease-modifying strategies for Parkinson's disease.
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.
authors.affiliation: 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.
authors.forename: Lorraine V
authors.initials: LV
authors.lastname: Kalia
authors.affiliation: Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.|Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Canada.
authors.forename: Suneil K
authors.initials: SK
authors.lastname: Kalia
authors.affiliation: 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.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*
chemical_list: D000978:Antiparkinson Agents
keywords: LRRK2; autophagy; gene therapy; mitochondria; neuroprotection