Cancer drug nilotinib could treat Parkinson's disease and restore movement in patients, finds study
A leukemia drug called nilotinib has shown promise in treating Parkinson's disease. The drug, also sold as Tasigna, recently passed its second clinical test that lasted 15 months.
Parkinson’s disease, a type of movement disorder, is the second most common neurodegenerative disease after Alzheimer’s. About 1% of the population at age 60 and 4% by age 80 have the disease. Patients show symptoms like tremors, rigidity, and difficulty walking in the early stages and develop brain decline in later stages.
The Georgetown trial, which included 75 patients with moderately advanced disease, responded well to the drug, according to the results published in JAMA Neurology. "Determining the safety of nilotinib in people with Parkinson's was our primary objective," explains Georgetown neurology associate professor Charbel Moussa, the senior author of the study, and director of the GUMC Translational Neurotherapeutics Program.
The drug shows potential in restoring movement in Parkinson's patients, as it replenished their levels of a brain chemical called dopamine, say researchers.
Patients with greater loss of cells that produce dopamine show symptoms of Parkinson's. These symptoms, however, can be controlled by certain medications.
For instance, levodopa, the most commonly used drug, gets converted into dopamine in the body. But too much of this chemical is associated with nausea and other side effects.
Other drugs such as pramipexole (Mirapex) mimic dopamine, tricking the brain into thinking that it has received the chemical. Still, there is no treatment for Parkinson's and researchers are on a hunt to find the ideal medication.
"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 periodically increasing drugs that mimic dopamine," says Moussa.
Further, these patients had lower levels of toxic proteins in the brain towards the end of the study. The drug could be achieving this feat by boosting the immune cells' ability of clearing the levels of toxic proteins produced from damaged brain cells. When patients take nilotinib, "You turn on the garbage disposal daily and you're able to get rid of that accumulation and hopefully see better function," Dr Fernando Pagan, MD, medical director of the GUMC Translational Neurotherapeutics Program and principal investigator of this study told NPR.
Of the 75 patients in the Georgetown trial, 88% of the participants completed the study. For 12 months, these patients were either given placebo or nilotinib. And in the next three months, participants did not receive either placebo or nilotinib.
The team evaluated the performance of the drug at six, 12 and 15 months. These results were then compared to the patient's health condition before the trial began.
Towards the end of the study, the team recorded low levels of toxic proteins found in the brains of Parkinson's patients — alpha-synuclein (20%) and tau (30%) — in those who took the drug.
Participants also showed an increase in their brain's dopamine reserves. "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," says Pagan.
Concerns over the trials
Another clinical trial, dubbed NiloPD, evaluating the same drug earlier this month found no such benefits. "These results are disappointing for both the patient and researcher communities. However, there are a number of other drugs in clinical development with better effects," Tatyana Simuni, from Northwestern University Feinberg School of Medicine, who was involved in this study, told MEA WorldWide (MEAWW).
"Both are phase II studies that enrolled 75 patients and both showed nilotinib is safe," Moussa told MEAWW, highlighting the similarities between the two studies.
But, there are differences, Moussa adds. "Our trial studied nilotinib for 15 months and the NiloPD trial studied drug effects for only 6 months. NiloPD has a very sloppy design and fails to properly measure desired outcomes. They have made several fatal design errors!" Moussa told MEAWW.
However, not all experts agree with the success of the Georgetown trial. It is not clear from the study whether the dopamine changes were caused by nilotinib or something else, Dr Joel Perlmutter, who directs the movement disorders program at Washington University School of Medicine in St Louis told NPR.
He adds that he is also concerned about the side effects, including heart problems, which were more frequent in people who got the drug than those who got a placebo. Nilotinib is known to cause heart problems in some leukemia patients.
All these doubts will be laid to rest during phase 3 of the studies. "Only phase III trials should draw final conclusions about clinical effects," Moussa told MEAWW.