Cancer Drug Nilotinib Shows Promise for Parkinson's Patients

A drug used to fight chronic myeloid leukemia might also relieve symptoms of Parkinson's disease, a new study finds.

In a phase 2 clinical trial, researchers found that the drug nilotinib (brand name: Tasigna) increased production of dopamine and halted decline in motor function. It was well-tolerated by most participants.

"We found that nilotinib is reasonably safe using doses 25% to 50% lower than the cancer dose," said lead researcher Dr. Charbel Moussa, an associate professor of neurology at Georgetown University in Washington, D.C.

"We also discovered that nilotinib increases the level of a brain chemical called dopamine that is lost or reduced in Parkinson's disease," he said.

Nilotinib also lowers levels of toxic proteins that lead to the slow death of dopamine neurons in the brain, Moussa said.

"After one year of treatment, the nilotinib group was stable and did not decline on both motor and non-motor clinical scales," he said.

Patients in the trial continued to take their regular medication, which may have affected how well nilotinib worked, Moussa said. It now needs to be studied independently for at least year, he added.

"These data are a green light to study nilotinib in a larger phase 3 trial to finally validate its clinical effects," Moussa said.

Parkinson's disease is a brain disorder that leads to shaking, stiffness and difficulty with walking, balance and coordination.

It occurs when nerve cells in a brain area that controls movement die. When they die, less dopamine is made, which causes the Parkinson's symptoms.

For the research, 75 Parkinson's patients were assigned to take either a placebo, 150 milligrams (mg.) of nilotinib, or 300 mg. of nilotinib. The study was double-blind, which meant neither patients nor scientists knew which medication was given.

Patients continued the regimen for 12 months, followed by three months in which they took neither placebo nor nilotinib.

In all, 88% finished the trial. Of those taking nilotinib, nine quit before the trial ended, two because of severe side effects, researchers said.

The drug carries a U.S. Food and Drug Administration (FDA) black-box warning, because it has been linked to sudden death at higher doses due to blocking of Abl tyrosine kinase, a protein needed for cellular function. Moussa said this doesn't appear to occur at the lower doses given in the trial.

His team also found that patients taking nilotinib had lower levels of two toxic proteins common in people with Parkinson's. Alpha-synuclein was reduced 20% and tau, 30%.

At the same time, levels of dopamine metabolites increased more than 50%. This suggests that getting rid of these toxic proteins increases effectiveness of the patient's dopamine.

Some patients taking nilotinib reported having better motor function and improved quality of life, researchers said.

They reported their findings online Dec. 16 in the journal JAMA Neurology.

But the co-author of an editorial published with the study said he doesn't think the findings warrant a phase 3 trial. He considers the drug too toxic for Parkinson's patients.

"The data does not support future demonstration of clinical efficacy and the changes in biomarkers are questionable," said Dr. Alberto Espay, a professor of neurology at the University of Cincinnati Gardner Center for Parkinson's Disease and Movement Disorders. "This attempt to repurpose nilotinib for the treatment of Parkinson's appears futile."

Another recent trial of nilotinib for treatment of Parkinson's disease (NILO-PD) found no clinically meaningful benefit for patients.

Espay pointed out that in this current trial, those who took the 300 mg. dose experienced a worsening in activities of daily living, as well as motor and mental function.

"The implication is that the justification for a phase 3 trial is tenuous at best, and with the recent announcement of the negative competing trial NILO-PD, to be discouraged," he said.

Funding for the trial came from a variety of sources. Georgetown University holds the patent for use of nilotinib to treat certain neurodegenerative diseases.

Novartis, the maker of nilotinib, provided the drug and the placebo for free.

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