with neurodegenerative diseases have found a new lease on life, thanks to a drug used for leukemia, according to findings presented this week at Neuroscience 2015 in Chicago, IL.
The drug, nilotinib, improved and even reversed impaired cognition, motor skills and non-motor function in patients withParkinson’s disease and Lewy body dementia, in a small phase 1 clinical trial.
It also significantly changed biomarkers, the toxic proteins linked to disease progression, accord to Dr. Charbel Moussa, PhD, and Dr. Fernando Pagan, PhD, both of Georgetown University Medical Center in Washington (GUMC), who conducted the preclinical research.
They gave nilotinib, a treatment for chronic myelogenousleukemia (CML), to 11-12 patients, increasing the dose from 150 to 300 mg a day over 6 months.
Previous studies have shown that the onset of dementia causes an increase in Tau and p-Tau in cerebrospinal fluid (CSF); and that as Parkinson’s worsens, it causes a decrease in α-synuclein and Abeta 40/42 in CSF.
In this study, Tau and p-Tau decreased significantly, suggesting the clearance of toxic proteins in the brain, while alpha-synuclein, amyloid beta-40/42 rose.
Dopamine production increased in some patients to the extent that their usual dopamine-sparing drugs prescribed for Parkinson’s (L-dopa therapies), could be lowered or stopped. Nilotinib appears to penetrate the blood-brain barrier in amounts greater than dopamine drugs.
Life-changing improvements experienced
All patients experienced benefits, and 10 of them reported meaningful clinical improvements, but the most dramatic was in observable behavior.
Most patients experienced an improvement in cognition, motor skills and non-motor function improvement (such as constipation). One individual confined to a wheelchair was able to walk again; three others who could not talk were able to hold conversations.
On stopping the nilotinib treatment, despite restarting their L-dopa therapies, patients again underwent cognitive and motor decline.
Alan Hoffman, PhD, who participated in the study, had fallen eight times in the 6 weeks before the trial, but during the 6 months of the study, fell only once. He says that his speech and thinking are improved.
He adds:
“Before the nilotinib, I did almost nothing around the house. Now, I empty the garbage, unload the dishwasher, load the washer and the dryer, set the table, even take responsibility for grilling. My wife says it’s life-changing for her and for my children and grandchildren. To say that nilotinib has made a change in our lives is a huge understatement.”
Participants with earlier stages of the disease responded best, as did those diagnosed with Lewy body dementia, often described as a combination of Parkinson’s and Alzheimer’s disease
Nilotinib in cancer and in Parkinson’s
Comparing the use of nilotinib in cancer and Parkinson’s, Dr. Moussa explains that in higher doses, the drug forces cancer cells into autophagy, a biological process that leads to the death oftumor cells.
Fast facts about Parkinson’s
Up to 1 million people in the US have Parkinson’s
Men are 1.5 times more likely to develop it than women
Prevalence increases with age, but 4% of people develop symptoms before age 50.
In smaller, daily doses, nilotinib turns on autophagy for 4-8 hours, long enough to clean out the cells without causing cell death. Then proteins that build up again will be cleared when the drug is given the next day.
In cancer treatment, doses of up to 800 mg a day cause serious side effects. In this treatment, the doses were far smaller, and the drug was well tolerated with no serious side effects, suggesting safe usage.
Limitations to the study include the fact that there was no control group for comparison, and that nilotinib was not compared with a placebo or other medications used to treat Parkinson’s.
The participants can continue taking nilotinib in an expanded study. Larger clinical trials for patients with Parkinson’s and other similar diseases, including Alzheimer’s, are planned for 2016.
Novartis, who provided the drug (Tasigna®), say the cost for the treatment of CML is about $10,360 a month for 800 mg daily. The dose used in this study was 150 and 300 mg daily.