The ongoing pursuit of neuroprotective therapies in Parkinson disease

Journal name:
Nature Reviews Neurology
Volume:
11,
Pages:
25–40
Year published:
DOI:
doi:10.1038/nrneurol.2014.226
Published online

Abstract

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD.

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Affiliations

  1. Sobell Department of Motor Neuroscience, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.

    • Dilan Athauda &
    • Thomas Foltynie

Contributions

D.A. researched data for article. D.A. and T.F. substantially contributed to discussion of content and wrote the article. T.F. reviewed and edited the manuscript before submission.

Competing interests statement

T.F. has received honoraria from Abbvie, Genus, Medtronic, Novartis, St. Jude Medical and Teva. D.A. declares no competing interests.

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  • Dilan Athauda

    Dilan Athauda is a Specialist Registrar in Neurology and a clinical research fellow in the Department of Functional Neurosurgery at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. He graduated from King's College, London, and is currently undertaking his PhD, which focuses on potential disease-modifying treatments in Parkinson disease.

  • Thomas Foltynie

    Thomas Foltynie is Senior Lecturer and Honorary Consultant Neurologist at the Sobell Department of Motor Neuroscience at the UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. He completed his neurology training in Cambridge, UK, where he undertook a PhD in the epidemiology and genetics of Parkinson disease (PD). At Queen Square, he is responsible for the treatment of patients with movement disorders—in particular, PD—who receive advanced treatments, such as deep brain stimulation (DBS), apomorphine and levodopa–carbidopa intestinal treatment. He is the lead clinician at UCL for a multicentre trial of fetal dopaminergic cell transplantation for PD, and for a proposed trial of DBS as a treatment for the cognitive problems associated with advanced PD. He is also leading a trial of DBS for the treatment of patients with severe Tourette syndrome. He has received grants from the Michael J. Fox Foundation, Brain Research Trust, Cure Parkinson's Trust, Parkinson's UK, and European Commission FP7.

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