Tasigna (nilotinib), an approved leukemia medication being tested as a repurposed treatment for Parkinson’s disease, was found to be safe and increased the levels of dopamine in the brain of patients with Parkinson’s disease, a Phase 2 trial shows.
The findings were reported in a study, “Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial,” and published in JAMA Neurology.
Tasigna, developed by Novartis, is approved by the U.S. Food and Drug Administration and the European Medicines Agency to treat adults with chronic myeloid leukemia, a type of blood cancer that typically affects older adults.
The medicine blocks the activity of a protein called BCR-ABL, which is known to support cancer development. But this protein is also intimately linked to several mechanisms in the brain, such as oxidative stress (cellular damage as a consequence of high levels of oxidant molecules) and alpha-synuclein-induced neurodegeneration, which play critical roles in Parkinson’s and other brain disorders.
For that reason, researchers wondered if Tasigna could be repurposed to treat Parkinson’s disease. Drug repurposing refers to the process of testing a medication with established safety in conditions other than those for which it was originally intended.
A pilot study in 12 individuals with Parkinson’s disease dementia and dementia with Lewy bodies suggested that this therapy could effectively treat Parkinson’s motor and non-motor symptoms, while also increasing dopamine metabolism (its use in the brain) and lowering alpha‐synuclein levels.
Subsequently, researchers in the new study sought to investigate the safety, tolerability, and pharmacokinetic properties of Tasigna in a placebo-controlled, Phase 2 trial (NCT02954978) carried out at Georgetown University Medical Center (GUMC). Pharmacokinetics refers to how a drug is absorbed, distributed, metabolized, and eliminated from the body.
The study enrolled 75 patients with moderate-to-severe Parkinson’s disease who were randomly assigned to receive one of two oral doses of Tasigna (150 or 300 mg daily), or a placebo, for a period of one year, followed by a washout period of three months, in which they stopped taking the medication or the placebo.
The mean dose of levodopa at enrollment was similar between groups.
Earlier findings from the study showed that treatment with a single low dose of Tasigna improved the brain’s ability to use dopamine stored in small vesicles in specific brain regions of Parkinson’s patients by reducing inflammation and the levels of toxic alpha-synuclein.
Most of the patients enrolled (88%) completed the study. A total of nine patients withdrew from the study, including two who had been assigned to the placebo, three who had been assigned to receive the lowest dose of Tasigna, and four who had been assigned to receive the highest dose of the medication. From these, two withdrew from the study due to serious adverse events.
Tasigna was considered reasonably safe and well-tolerated, with most adverse events being mild or moderate in severity. The most common non-serious adverse events included falls, and musculoskeletal, respiratory, and skin conditions. Gastrointestinal and heart problems were less common.
In a secondary exploratory analysis of biomarkers, the investigators found that patients treated with Tasigna experienced a reduction in the levels of two toxic proteins that are considered hallmarks of Parkinson’s disease: a 20% decrease in alpha-synuclein and 30% reduction in tau.
In addition, they discovered that those taking Tasigna had an increase of more than 50% in the levels of dopamine (the brain chemical missing in those with Parkinson’s disease), suggesting that reducing the levels of toxic proteins could help the brain to use dopamine more effectively.
Those taking Tasigna performed better on motor tests and tended to have better scores in the PDQ-39 questionnaire (a measure of quality of life) compared to those treated with the placebo.
“We see that subjects on nilotinib performed better overall on motor testing and had a better quality-of-life measurement during the study than the placebo group. These are important observations suggesting that nilotinib stabilized the disease — a potential disease modifying effect that we haven’t observed with any other agents,” Fernando Pagan, MD, medical director of the GUMC Translational Neurotherapeutics Program and principal investigator of the study, said in a press release.
“These clinical findings need confirmation through larger studies with more diverse populations,” added Pagan, who also directs the Movement Disorders Clinic at MedStar Georgetown University Hospital.