Parkinson’s Patients Sought for Phase 2a Trial Testing Repurposed Therapy Nilotinib

Parkinson’s Patients Sought for Phase 2a Trial Testing Repurposed Therapy Nilotinib

A new Phase 2a clinical trial, funded by The Michael J. Fox Foundation (MJFF), is now recruiting Parkinson’s disease patients to test the safety and tolerability of nilotinib, an approved treatment for chronic myelogenous leukemia (CML) that is now being repurposed for Parkinson’s disease.

Nilotinib, marketed as Tasigna for CML, is a tyrosine kinase inhibitor that blocks the c-Abl protein in leukemia cells with an abnormal chromosome, called the Philadelphia chromosome, stopping them from growing. But studies suggest that c-Abl also is involved in cellular pathways associated with Parkinson’s disease, suggesting that nilotinib could hold promise for this neurodegenerative disease.

The trial aims to enroll a total of 75 people with moderate-to-advanced Parkinson’s and will be conducted in a maximum of 25 clinical sites across the United States. Patients willing to participate are encouraged to visit the Fox Trial Finder to view a list of recruiting sites and eligibility criteria.

Participants will be randomized to daily doses of nilotinib or placebo for a period of six months. They will be closely monitored during the trial period and for an additional eight weeks after all treatments ceased.

The results will allow researchers to evaluate both nilotinib’s safety and tolerability, and to determine the therapy’s maximum tolerated dose.

The effectiveness of nilotinib for halting Parkinson’s symptoms and/or disease progression will be determined via a comprehensive analysis that includes complete motor, cognitive, and biological (i.e., blood and spinal fluid) tests.

If researchers find conclusive proof of nilotinib’s safety, a second trial is set up to include s60 participants with early Parkinson’s disease to test nilotinib for a period of 12 months at the highest tolerated daily dose. The trial also will include a placebo control group.

Principal investigator Tanya Simuni, MD, professor of neurology and head of the division of movement disorders at Northwestern University Feinberg School of Medicine, is leading the trial. It is set up with the collaboration of the Parkinson Study Group, which is the largest non-profit scientific network of Parkinson’s disease centers in North America.

Nilotinib, developed by Novartis, is an example of drugs that are being repurposed (aka “repositioned”) for Parkinson’s disease. This strategy has several advantages, as approved drugs for another condition are already known to be safe in humans. As a result, repurposed drugs usually can skip Phase 1 clinical testing, but still need to go through Phase 2 and Phase 3 trials to determine its effectiveness in other disease settings.

“Repurposing is a promising path to new Parkinson’s treatments, but we must demonstrate the safety and efficacy of therapies specifically for PD,” Todd Sherer, PhD, CEO at MJFF, said in a press release. “As part of our no-stone-unturned approach, The Michael J. Fox Foundation pursues every avenue, including repurposing, to accelerate breakthroughs for patients who urgently need them.”


  1. I note that one of the goals of this clinical trial is “to determine the therapy’s maximum tolerated dose”. I suggest that the goal should be to determine the maximally effective dose of nilotinib for the slowing or reversing of Parkinson disease (PD). The theoretical mechanism of action, as confirmed in murine studies, is the autophagic clearance of alpha-synuclein from the cytoplasm of CNS neurons, which occurs at low concentrations of nilotinib. At higher concentrations, autophagic apoptosis is triggered, a desired result in cancer chemotherapy, but not in PD. As a PD patient myself, I would want to stay well below the dose of nilotinib that causes intolerance due to the death of more neurons. We should aim to learn the maximally effective dose, as measured by clinical improvement of PD, rather than the maximum tolerated dose, which may be the dose at which neuronal apoptosis is triggered. Aiming to learn the maximally effective dose of nilotinib, rather than the maximally tolerated dose, should also minimize other side-effects of this therapy, including torsade des pointes and leucopenia.

  2. Gary Rafaloff says:

    As I’m sure you know, Phase 2 trials are designed to measure safety and dose as primary outcomes. Efficacy is normally only studied as a secondary outcome, which is the case with the NILO-PD trial.

    • I agree, but the point I intended to convey is that nilotinib has dose-dependent adverse effects which, at the high end of the dose range used for treating leukemia, may cause paradoxical progression of Parkinson disease (PD). Because I have high hopes for major clinical benefits for low-dose nilotinib, including the slowing or reversal of PD brain pathology, I am worried that Phase 2 may end up being terminated early if the “maximum tolerated dose” is pursued too aggressively.

  3. Pearl Fu says:

    I wrote a long comment. It disappeared when you printed and I gave the wrong email address. Have to rush to be in the event. Want to participate in a trial to conquer Parkinson’s ailment. I have had 17 years. Forced myself to be active and exercise seven days a week at the YMCA, physical therapy, yoga, water exercise, walking, with DVD. I write a monthly column in the senior news magazine, giving tips on how to overcome stress. Be happy and try all content new techniques. Have many fans. Hope you can use me in a trial in Roanoke Virginia. I no longer drive, but love to promote and be on the screen. Have a degree in performing arts and music from the former Peabody Conservatory of music which is now Johns Hopkins University,

  4. Frank Mundo says:

    Michael J. Fox has sat on testing of nilotinib for MORE than TWO YEARS since initial (positive) clinical tests (completed and published mid 2015). The situation really calls into question whether or not MJFF is the appropriate funding foundation into which to direct funds. With the great promise of this drug for treatment of PD, its a real tragedy that arguments about “control and who gets the credit” have stood as obstacles to getting moving on Clinical Tests . . . so desperately needed by people (like me) who suffer with the disease.

  5. I share Frank Mundo’s impatience for a treatment that halts or reverses the pathological CNS damage caused by PD. Professor Charbel Moussa, chair of Neurodegenerative Disease research at Georgetown Medical School, proposed that low-dose nilotinib could stimulate autophagic clearance of alpha-synuclein overload from CNS neurons, and thereby halt or reverse the progression of PD. His group first confirmed this theory in Parkinsonian mice, and they conducted the phase-1 open-label pilot study which produced dramatic and credible anecdotes of disease reversal in humans with advanced PD.

    Donations to Georgetown Medical School, can be earmarked for the Phase II clinical study of nilotinib to treat PD, run by Dr. Moussa and Dr. Pagan. If their work confirms the first effective disease-modifying treatment for PD and related diseases, Moussa and colleagues will surely be awarded the Nobel Prize, regardless of how many others joined their efforts later.

    Like you, I am desperate for a curative treatment before I lose too many more neurons; it makes sense for us to contribute directly to the work of Moussa and Pagan, who may be so close to the threshold of success. But, if our hopes for nilotinib meet with unexpected disappointment, Fox and the other endowed foundations will continue the fundamental work of laying the groundwork for future breakthroughs in PD research.

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