- Investigators will focus on safety for long-term use in non-cancer patients
- Partners aim to design and co-fund a multi-site trial to begin in 2017; trial endpoints would include precise biological measures of drug activity as well as symptomatic response
- Patients and clinicians urged to proceed with caution
NEW YORK, GRAND RAPIDS and LONDON, UNITED KINGDOM -- The Michael J. Fox Foundation for Parkinson's Research (MJFF), Van Andel Research Institute (VARI) and The Cure Parkinson's Trust (CPT) today announced plans to collaborate on the clinical development of nilotinib, a chronic myelogenous leukemia drug that has shown potential in preliminary studies as a treatment for Parkinson's disease. As part of these efforts, the organizations aim to design and co-fund a therapeutic development program including a double-blind, placebo-controlled clinical trial of nilotinib expected to begin in 2017.
"We are enthusiastic about further investigating early clinical results that indicated some level of nilotinib safety and tolerability in Parkinson's patients," said Todd Sherer, PhD, chief executive officer of MJFF, one of three authors of an editorial published today in the Journal of Parkinson's Disease (JPD). Co-authored by Sherer, Patrik Brundin, MD, PhD, director of VARI's Center for Neurodegenerative science and co-editor-in-chief of JPD, and Richard Wyse, MD, director of research and development at CPT, the editorial summarizes the current status of nilotinib for Parkinson's, acknowledging the promise of intriguing clinical and pre-clinical findings but urging caution on the part of patients and clinicians until more research is done.
Collaboration Aims to Verify and Expand on Previous Nilotinib Findings
The goal of the MJFF/VARI/CPT collaboration is to advance nilotinib as a potentially disease-modifying and/or symptomatic Parkinson's treatment by first and foremost expanding on early safety findings and potential side effects in order to better understand the implications of long-term use of nilotinib in non-cancer patients.
The program also will rigorously address early-stage preclinical and clinical findings about the drug. Earlier studies have demonstrated some preliminary data on measures of drug penetration into the brain (as measured in spinal fluid) and exploratory biochemical measures. The MJFF/VARI/CPT study aims to verify and expand on these findings.
Preclinical studies have shown that nilotinib may protect neuronal cells from Parkinson's pathology by inhibiting the activity of a protein known as c-Abl, but additional work is required to understand the relationship between nilotinib dosing and c-Abl activity.
The role of c-Abl as a cancer driver in myelogous leukemia is well known and, as recent work by others in the field has demonstrated, it may also play a role in Parkinson's disease. The study also aims to explore and independently verify nilotinib's potential to treat Parkinson's symptoms.
Patients are encouraged to create a profile on Fox Trial Finder ( www.foxtrialfinder.org ) to be notified if they are a likely match for the planned nilotinib trial or other trials in need of research volunteers.
Patients and Clinicians Urged to Proceed with Caution
There is reason for optimism about the promise of nilotinib in Parkinson's disease, both as a therapy that might reduce symptoms in the short term and potentially even as a disease-modifying treatment (one capable of slowing or stopping Parkinson's progression, something no current treatment can do). Nonetheless, patients and clinicians are urged to wait for further safety data before considering adding the drug to their treatment regimens at this time. There is not yet enough information to assert that it works in Parkinson's and, perhaps most critically, that it is safe to take long-term.
"We are enthusiastic about this partnership, which demonstrates the commitment of those involved to leave no stone unturned in the quest to find better treatments for Parkinson's," said Tom Isaacs, co-founder of The Cure Parkinson's Trust. "It is imperative that we work urgently with the Parkinson's community — my fellow patients as well as drug developers — as we continue vetting nilotinib's potential to address the medical needs of people with Parkinson's in a safe and effective manner."
MJFF, CPT and VARI have long recognized the potential of repositioned drugs — that is, drugs approved to treat other diseases, which have also shown promise in Parkinson's — to significantly cut down on the time and cost of moving new Parkinson's treatments from the lab to clinical care. An investigation of the high-blood-pressure drug isradipine funded by MJFF from 2007–2015 has recently entered Phase III clinical testing. CPT and VARI have partnered since 2014 on their Linked Clinical Trials (LCT) initiative, which is dedicated to funding the development of repositioned medications with potential to slow or reverse Parkinson's disease. Through LCT, The Cure Parkinson's Trust and Van Andel Research Institute have committed to work with The Michael J. Fox Foundation to further explore the possibility of nilotinib as a Parkinson's treatment, and to educate Parkinson's patients and families about the drug.
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About The Michael J. Fox Foundation for Parkinson's Research
As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, industry leaders, government research funders and regulators, clinical trial participants, donors and volunteers. In addition to funding more than $600 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. The Foundation increases the flow of participants into Parkinson's disease clinical trials with its online tools Fox Trial Finder and Fox Insight; sponsors a landmark, international study to find reliable and consistent biomarkers of Parkinson's progression; promotes Parkinson's awareness through high-profile events and outreach; advocates for state and federal policies that support medical research and increased access to health care; and coordinates the involvement of thousands of Team Fox members and grassroots volunteers around the world.
About Van Andel Research Institute
Van Andel Institute (VAI) is an independent biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 360 scientists, educators and staff. Van Andel Research Institute (VARI), the research division of VAI, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson's and other diseases and translating those findings into effective therapies. The Institute's scientists work in on-site laboratories and participate in collaborative partnerships that span the globe.
About The Cure Parkinson's Trust
The Cure Parkinson's Trust was set up in 2005 by four people living with the condition. It has one bold aim – to cure Parkinson's. People living with Parkinson's shape the charity's policies and approach. Its innovative Linked Clinical Trials Programme focuses on drug repurposing, prioritizing potentially disease modifying treatments and moving them forward to clinical trial. Nilotinib has been explored through this programme since 2012This programme has been developed in collaboration with the Van Andel Institute and to date six trials are underway on drugs used in other conditions, and two regenerative medicine trial, of which show the potential to slow, stop or reverse Parkinson's. www.cureparkinsons.org.uk