The drug, nilotinib (known as Tasigna® by Novartis) also led to statistically significant and encouraging changes in toxic proteins linked to disease progression.
Charbel Moussa, MD, PhD, who directs Georgetown’s Laboratory of Dementia and Parkinsonism, conducted the preclinical research that led to the discovery of nilotinib for the treatment of neurodegenerative diseases.
To conduct the clinical study, he partnered with Fernando Pagan, MD, a GUMC associate professor of neurology who directs the Movement Disorders Program at MedStar Georgetown University Hospital.
“To my knowledge, this study represents the first time a therapy appears to reverse – to a greater or lesser degree depending on stage of disease – cognitive and motor decline in patients with these neurodegenerative disorders,” says Pagan. “But it is critical to conduct larger and more comprehensive studies before determining the drug’s true impact.”
The investigators report that one individual confined to a wheelchair was able to walk again and that three others who could not speak were able to hold conversations.
Pagan notes there was no control group for comparison in the study, and that the drug was not compared with a placebo or other medications used to treat Parkinson’s.
But the researchers report that during use of the medication by the participants, production of dopamine increased in many patients, requiring doses of L-dopa and other dopamine-sparing drugs used to treat Parkinson’s to be lowered or stopped.
Stopping nilotinib treatment appears to lead to cognitive and motor decline despite reinstating L-dopa therapies.
The study’s primary objective was to test safety.
“The use of nilotinib in doses much smaller than are used to treat cancer, which is up to 800 mg daily, was well tolerated with no serious side effects,” Pagan explains. “The dose used in this study was 150 and 300 mg daily.”
The researchers also found that the drug penetrates the blood-brain barrier in amounts greater than dopamine drugs.
The observed efficacy in cognition, motor skills and non-motor function improvement (such as constipation) for many patients was the most dramatic result, Pagan notes.
“Study participants with earlier stage disease responded best, as did those diagnosed with Lewy body dementia, often described as a combination of Parkinson’s and Alzheimer’s diseases,” he says.
Alan Hoffman, a professor emeritus of social science education at Georgia State University, was diagnosed with Parkinson’s disease in 1997. He says he participated in several clinical trials with no benefit until he enrolled in Pagan’s study.
“Before the nilotinib, I did almost nothing around the house,” he says. “Now, I empty the garbage, unload the dishwasher, load the washer and the dryer, set the table, even take responsibility for grilling.”
In the three weeks prior to enrolling in the study, Hoffman says he fell eight times, but he only fell once during six months on the study. His speech has improved, as has his thinking.
“My wife says it’s life-changing for her and for my children and grandchildren,” Hoffman says. “To say that nilotinib has made a change in our lives is a huge understatement.”
Moussa, an inventor on a Georgetown University patent application for nilotinib and other similar drugs for neurodegenerative diseases, notes that the research went to clinical trials only two years after his initial discovery.
He first set out to find approved cancer drugs that could penetrate the blood-brain barrier and turn on the “garbage disposal machinery” inside neurons to clear toxic intracellular proteins and prevent their accumulation within, or secretion outside of, brain cells.
“A lot of institutions talk about expediting the translation of research from the lab to the bedside, but it doesn't happen quickly very often,” Moussa says. “This is a solid example of how that is possible and why it is so important.”
Patients Continue Treatment
Hoffman and other patients in the clinical trial can continue taking nilotinib as part of an expanded access study. Georgetown researchers are now planning larger clinical trials with nilotinib for patients with Parkinson’s and other similar diseases including Alzheimer’s disease, likely to begin in 2016.
The phase I study received philanthropic funding and was supported by the Georgetown-Howard Universities Center for Clinical and Translational Science.