Publication date: Mar 13, 2019
Laboratory analysis from the first arm of a phase II clinical trial testing the use of nilotinib in patients with Parkinson’s disease demonstrates precisely how the agent increases levels of dopamine in the brains of study participants, says a research team at Georgetown University Medical Center.
In the journal Pharmacology Research Perspectives, investigators report that a single low dose of the leukemia drug, nilotinib (Tasigna by Novartis), reduces levels of a toxic protein that prevents the brain from utilizing dopamine that is stored in tiny vesicles, or pockets, in brain areas that may control movement.
The researchers say nilotinib appears to rev up the ability of immune cells within the brain to reduce the constant flow of the misshapen alpha-synuclein protein produced by damaged neurons, allowing normal alpha-synuclein to facilitate release of stored dopamine.
This is unprecedented for any drug now used to treat Parkinson’s disease,” says the study’s senior author, Charbel Moussa, MBBS, Ph. D., director of the Laboratory for Dementia and Parkinsonism, and scientific and clinical research director of the Translational Neurotherapeutics Program at Georgetown University Medical Center.
Researchers examined levels of dopamine breakdown products, 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the CSF that bathes the brain and spinal cord of patients, after nilotinib or placebo.
After a single dose of nilotinib, they found DOPAC and HVA were elevated in patients who received nilotinib compared to placebo, suggesting the brain was utilizing substantially more dopamine.
In preclinical studies, Moussa says nilotinib appears to trigger brain cells (including immune cells and neurons) to attack the misfolded protein that is being produced, allowing normal alpha-synuclein to access and release dopamine from storage vesicles.
Fernando Pagan, MD, principal investigator of the clinical trial and first author of the paper says the scientific evaluation of nilotinib’s effect suggest it can reduce toxic alpha-synuclein and brain inflammation, while protecting dopamine and dopamine-secreting neurons.