Researchers at the Georgetown University Medical Center reported nilotinib (Tasigna® by Novartis), a treatment for chronic myelogenous leukemia (CML), successfully treated Parkinson’s disease and Lewy body dementia patients in a Phase I trial. The complete results were presented during the annual meeting of the society of Neuroscience, Neuroscience 2015, held in Chicago on October 17.
The six-month trial was completed by 11 of the 12 patients that initiated treatment with nilotinib, all reporting positive outcomes and 10 of them reporting significant clinical improvement. Disease biomarkers in the cerebrospinal fluid were also evaluated and positive changes were found for alpha-synuclein (α-synuclein), amyloid beta-40/42 (Abeta-40/42), dopamime and tau protein, a sign of toxic protein clearance from the brain. Dopamine production increased in several patients, and discontinuation of nilotinib led to deterioration of cognitive and motor skills even with L-dopa therapies. Moreover, the daily dose administered in the trial (150 to 300 mg daily), was much lower than that used for leukemia treatment and was well-tolerated with no serious side effects. Results on observed cognitive, motor, and non-motor function were considered impressive: one patient confined to a wheelchair was able to walk again and three other patients with speech impairments regained their speech capacity.
Dr. Charbel Moussa, MD, director of Georgetown’s Laboratory of Dementia and Parkinsonism, selected nilotinib for the Parkinson’s trial after conducting a preclinical search of an anti-cancer drug that would penetrate the blood-brain barrier and restore the recycling activity of neurons, this way preventing accumulation of waste proteins and formation of toxic structures intracellularly or extracellularly. “When used in higher doses for CML, nilotinib forces cancer cells into autophagy — a biological process that leads to the death of tumor cells. The dose used in CML treatment is significantly higher than what we used in our Parkinson’s study,” Dr. Moussa explained. “It appears that in smaller doses once a day, nilotinib turns on autophagy for about four to eight hours — long enough to clean out the cells without causing cell death. Then proteins that build up again will be cleared when the drug is given again the next day.”
The researchers’ future plans include larger clinical trials with Parkinson’s and other neurodegenerative disease patients, such as Alzheimer’s. Importantly, this study was not conducted with a control group, placebo, or patients using other Parkinson’s disease medication, so results need further validation.