Review

Neurotherapeutics

, Volume 11, Issue 1, pp 6-23

Pathogenesis-Targeted, Disease-Modifying Therapies in Parkinson Disease

  • Amaal AlDakheelAffiliated withMorton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University Health Network
  • , Lorraine V. KaliaAffiliated withMorton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University Health Network
  • , Anthony E. LangAffiliated withMovement Disorders Unit, Toronto Western Hospital Email author 

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Abstract

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