Leukemia Drug Provides Benefits in PD, Researchers Find

Samantha DiGrande

Parkinson disease (PD) is the second-most common neurodegenerative disorder that causes both motor and nonmotor symptoms. PD is also characterized by the loss of dopamine-producing neurons, which contributes to motor dysfunction.

A recently published study looked to evaluate the effect of a single dose of nilotinib (Tasigna) in patients with PD. While nilotinib is FDA-approved for the treatment of adult patients with chronic myeloid leukemia and not PD, the drug is able to penetrate the blood-brain barrier and reduce inflammation as well as lower levels of a toxic protein that prevents the brain from utilizing dopamine stored in vessels in areas of the brain that may control movement. Nilotinib can also increase dopamine levels and in a 12-patient pilot study, it appeared to improve the motor and cognitive outcomes of patients with PD and dementia. 

In the analysis of 1 arm of a phase 2 clinical trial published in Pharmacology Research & Perspectives, researchers found that a single low dose of nilotinib increased levels of dopamine in the brains of study participants. The authors discovered that nilotinib appeared to increase the ability of immune cells within the brain to reduce the flow of “misshapen” alpha-synuclein protein produced by damaged neurons, allowing normal alpha-synuclein to release stored dopamine.

“We detect the drug in the brain producing multiple effects, including improving dopamine metabolism–reducing both inflammation and toxic alpha-synuclein. This is unprecedented for any drug now used to treat Parkinson’s disease,” said study author Charbel Moussa, MBBS, PhD, director, Laboratory for Dementia and Parkinsonism, in a statement.

In order to analyze the effects of the drug within PD patients, the authors examined the levels of certain dopamine breakdown products within the brain after niliotinib or placebo were administered. Specifically, 3,4-Dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) found in the cerebral spinal fluid (CSF) were evaluated.

Without nilotinib treatment, DOPAC and HVA were seen at low levels in the CSF of all patients, which suggests that a low level of dopamine is being used in the brain. After a single dose of nilotinib, the researchers found that DOPAC and HVA were elevated in patients who received the treatment.

“When the drug is used, levels of these breakdown molecules quickly rise. This is what we also found in our preclinical studies and proof of concept clinical trial,” said Moussa. 

Though final conclusions cannot be made until the results of the full trial are completed, researchers were hopeful about the intermediary results. “This is exciting because this kind of potential treatment for Parkinson’s could increase use of a patient’s own dopamine instead of using or increasing drugs that mimic dopamine,” he said. 

Pagan F, Hebron M, Wilmarth B, et al. Pharmacokinetics and pharmacodynamics of a single dose of nilotinib in individuals with Parkinson’s disease [published March 12, 2019]. Br Pharm Soc. doi:10.1002/prp2.470.
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