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Linked Clinical Trials Initiative

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Overview

The Linked Clinical Trials (LCT) initiative identifies potential new therapies for Parkinson’s disease from drugs approved to treat other conditions and that have demonstrated neuroprotective effects in preclinical experiments. By using drugs that already have passed rigorous safety and toxicology trials, LCT aims to significantly cut the amount of time it takes for a potential treatment to move from the laboratory to clinical trials and, ultimately, to the patient. This approach also can reduce the cost of bringing new Parkinson’s disease treatments to fruition.

The expense of clinical trials seriously hampers translation from the lab to the clinic. More than 90 percent of drugs fail during development (Brundin et al 2013). Those that do pass early trials face a long road before they can be used to treat patients—it can take more than a decade and more than $1 billion to move a drug from development to the market.

This is where LCT comes in. A program spearheaded by Parkinson’s research charity The Cure Parkinson’s Trust in collaboration with Van Andel Research Institute (VARI), LCT is made up of leading Parkinson’s disease experts from around the world. Members form a committee that prioritizes promising new therapies for clinical trials in hopes of shortening the time it takes to get new treatments to patients. It is chaired by Patrik Brundin, M.D., Ph.D., VARI’s associate director of research and director of the Center for Neurodegenerative Science.

Clinical trials

The Linked Clinical Trials committee meets in person annually to examine dozens of potential therapeutics and selects those that have the highest likelihood of successfully treating Parkinson’s disease. The drugs listed below are currently in clinical trials and have been chosen by the committee based on drug safety, the drug’s ability to pass through the blood-brain barrier, mode of action, ability to measure the drug’s effectiveness, and demonstrated success in preclinical models (Brundin et al 2013).  

Ambroxol

One of the latest trials to get underway focuses on the respiratory drug ambroxol. Work conducted by the trial’s principal investigator, Anthony Schapira, M.D., D.Sc., demonstrated that ambroxol improves the function of a protein that plays a key role in cellular “trash removal” processes. Recent evidence suggests these processes are linked to neurodegenerative disease onset and progression. The proof-of-concept trial is based at Royal Free Hospital in London, UK, and includes a cross section of people with Parkinson’s, including those with inherited forms of the disease.

Simvastatin

Simvastatin treats high cholesterol but could have applications in Parkinson’s disease due to its anti-inflammatory properties. Simvastatin’s effects in Parkinson’s are the subject of a clinical trial that is underway across 21 centers in the United Kingdom and is led by University of Plymouth.

Exenatide

Exenatide is a type 2 diabetes drug that has shown great promise as a neuroprotective agent in laboratory experiments. Parkinson’s patients given exenatide for one year continued to show improvements compared to the control group a year after discontinuing treatment. Trials are ongoing at University College London. Other trials using exentide are planned to explore different stages and aspects of Parkinson’s.

Liraglutide

Liraglutide belongs to a class of drugs called GLP-1 agonists and prompts the release of insulin, thereby lowering glucose levels in the blood when bound to its receptor. Recent laboratory findings suggest that when liraglutide activates these receptors in the brain, the drug provides protection against degenerative damage to key brain cells, specifically those affected in Parkinson’s disease.

A trial is now underway at Cedars-Sinai Los Angeles led by Michele Tagliati, M.D.

For more information on these trials and other prioritized drugs in the pipeline, please visit The Cure Parkinson’s Trust here. Please note, although Van Andel Research Institute is involved in clinical trials, the Institute does not treat patients and does not conduct trials onsite. Information about additional clinical trials beyond those supported by the Linked Clinical Trials initiative can be found at Clinical Trials.gov.

Linked Clinical Trials committee

Linked Clinical Trial committee members hail from some of the leading research organizations in the world and bring with them a vast range of experience studying all facets of Parkinson’s disease. Committee members meet annually to evaluate potential treatments that may be repositioned to treat Parkinson’s disease. 

Team Members

Patrik Brundin, M.D., Ph.D. (Committee chair)
Associate Director of Research
Director, Center for Neurodegenerative Science
Jay Van Andel Endowed Chair in Parkinson’s Research
Van Andel Research Institute, Grand Rapids, USA

Roger Barker, MBBS, MRCP, Ph.D.
Professor of Clinical Neuroscience
University of Cambridge, Cambridge, U.K.

Flint Beal, M.D.
University Professor, Professor of Neuroscience, Professor of Neurology
Cornell University, Ithaca, USA

Ted Dawson, M.D., Ph.D.
Leonard and Madlyn Abramson Professor of Neurodegenerative Diseases
Johns Hopkins University, Baltimore, USA

Jeffrey Conn, Ph.D.
Lee E. Limbard Professor of Pharmacology
Director, Vanderbilt Center for Neuroscience Drug Discovery
Vanderbilt University, Nashville, USA

Howard Federoff, M.D., Ph.D.
Executive Vice President for Health Sciences
Executive Dean, School of Medicine
Georgetown University, Washington, D.C., USA

Karl Kieburtz, M.D., MPH
Robert J. Joynt Professor in Neurology
Director of Clinical and Translational Science Institute, University of Rochester Medical Center
University of Rochester, Rochester, USA

Dimitri Krainc, M.D.
Chair, Department of Neurology
Director, Center for Rare Neurological Diseases
Aaron Montgomery Ward Professor
Northwestern University Feinberg School of Medicine, Chicago, USA

Andrew Lees, M.D., F.R.C.P., FMedSci
Professor of Neurology, The National Hospital for Neurology and Neurosurgery, Queen’s Square
Emeritus Director, Reta Lila Weston Institute of Neurological Sciences, University College London Institute of Neurology
University College London, U.K.

Mark Mattson, Ph.D.
Senior Investigator
Chief, Laboratory of Neurosciences
Chief, Cellular and Molecular Sciences Section
Director of the Molecular Neurobiology Lab, Massachusetts General Institute for Neurodegenerative Disease
National Institut on Aging, Balitmore, USA

Michael Schwarzschild, M.D., Ph.D.
Professor of Neurology, Harvard Medical School
Director of the Molecular Neurobiology Lab, Massachusetts General Institute for Neurodegenerative Disease
Massachusetts General Hospital and Harvard University, Boston, USA

David Simon, M.D., Ph.D.
Director, Parkinson’s Disease and Movement Disorders and the National Parkinson Foundation Center for Excellence, Beth Israel Deaconess Medical Center
Associate Professor of Neurology, Harvard Medical School, Boston, USA

David Sulzer, Ph.D.
Professor
Departments of Psychiatry, Pharmacology, and Neurology
Columbia University Medical Center, New York, USA

Caroline Tanner, M.D., Ph.D., F.A.A.N.
Director, Parkinson’s Disease Research Education and Clinical Center, San Francisco Veterans Affairs Medical Center
Professor of Neurology, University of California, San Francisco, USA

John Trojanowski, M.D.
William Maul Measey-Truman G. Schnabel Professor of Geriatric Medicine and Gerontology
University of Pennsylvania, Philadelphia, USA

Richard Wyse, M.D.
Director of Research and Development
The Cure Parkinson’s Trust, UK

Related publications

Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Kahan J, Ell P, Whitton P, Wyse R, Isaacs T, Lees A, Limousin P, Foltynie T. 2014. Motor and cognitive advantages persist 12 months after exendatide exposure in Parkinson’s disease. J Parkinson’s Dis 4(3):337–344.   

McNeill A, Magalhaes J, Shen C, Chau KY, Hughes D, Mehta A, Foltynie T, Cooper MJ, Abramov AY, Gegg M, Schapira AHV. 2014. Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells. Brain 137(5):1481–1495.

Brundin P, Barker R, Conn PJ, Dawson TM, Kieburtz K, Lees AJ, Schwarzschild M, Tanner CM, Isaacs T, Duffen J, Matthews H, Wyse RKH. 2013. Linked Clinical Trials—The development of new clinical learning studies in Parkinson’s disease using screening of multiple prospective new treatments. J Parkinson’s Dis 3:231-239.

Schapira AHV, Gegg ME. 2013. Glucocerebrosidase in the pathogenesis and treatment of Parkinson’s disease. Proc Natl Acad Sci U S A 110(9):3214–3215.

Dodson MW, Guo Ming. 2007. Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson’s disease. Curr Opin Neurobiol 17(3):331–337.

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