, Volume 11, Issue 1, pp 6–23 | Cite as

Pathogenesis-Targeted, Disease-Modifying Therapies in Parkinson Disease

  • Amaal AlDakheel
  • Lorraine V. Kalia
  • Anthony E. Lang


Parkinson disease is an inexorably progressive neurodegenerative disorder. Multiple attempts have been made to establish therapies for Parkinson disease which provide neuroprotection or disease modification—two related, but not identical, concepts. However, to date, none of these attempts have succeeded. Many challenges exist in this field of research, including a complex multisystem disorder that includes dopaminergic and non-dopaminergic features; poorly understood and clearly multifaceted disease pathogenic mechanisms; a lack of reliable animal models; an absence of effective biomarkers of disease state, progression, and target engagement; and the confounding effects of potent symptomatic therapy. In this article, we will review previous, ongoing, and potential future trials designed to alter the progressive course of the disease from the perspective of the targeted underlying pathogenic mechanisms.

Key Words

Clinical trials disease modification neuroprotection Parkinson disease pathogenesis 



LVK is supported by a Canadian Institutes of Health Research Clinician-Scientist Award. AEL holds the Jack Clark Chair in Parkinson’s Disease Research at the University of Toronto. The authors have no real or perceived conflicts of interest. Full conflict of interest disclosures are available in the electronic supplementary material for this article.

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Disclosure forms provided by the authors are available with the online version of this article.

Since the review and acceptance of this manuscript, the NINDS has stopped the NET‐PD long‐term study of creatine for treatment of early stage PD. According to the NET‐PD website, an interim analysis revealed evidence for futility. Continued follow‐up of subjects was not expected to demonstrate a statistically significant difference between creatine and placebo. Hence, the study’s Data Safety Monitoring Board recommended termination of the study.

Supplementary material

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2013

Authors and Affiliations

  • Amaal AlDakheel
    • 1
  • Lorraine V. Kalia
    • 1
  • Anthony E. Lang
    • 2
  1. 1.Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s DiseaseToronto Western Hospital, University Health NetworkTorontoCanada
  2. 2.Movement Disorders UnitToronto Western HospitalTorontoCanada

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