Cancer drug may offer hope for Parkinson's and dementia patients

September 11, 2016

ROCHESTER – A local doctor is helping to treat a patient with Lewy body dementia, using an off-use drug recently tested on dementia patients, and he and the husband of the patient say there is no reason why the ongoing controversy between research organizations and the lack of support from insurance companies should stand in the way of the drug helping patients now, instead of years from now.

A small pre-clinical trial done in 2015 at Georgetown University showed remarkable results in using the FDA-approved leukemia drug nilotinib to treat patients with late stage Parkinson’s disease and dementia. The results of the trial showed marked improvement in both the cognitive and mobility capabilities of the patients.

In a press release from Georgetown University, researchers indicated that further and more controlled clinical trials needed to be completed before they would recommend nilotinib as being safe to treat dementia and Parkinson’s patients.

After much research, Dr. Terry Bennett agreed to prescribe nilotinib to treat Salem resident Madeline Carano, at the request of her husband of 65 years, Don Carano. Both say the results of the study are too compelling to wait because by the time the trials are completed years will be lost to patients who need help now.\

Carano is so devoted to his wife and her care that he is paying out-of-pocket, a significant amount of money monthly to treat his wife, under Bennett’s supervision. He has signed a hold-harmless document with Bennett.

“Why are we not doing an accelerated program to get this job done?” asked Bennett. “The results of this FDA-approved drug are incredible. Dementia patients are making too much of a tau protein and this drug basically dissolves them. It is so effective, that people’s conditions are reversing back to an earlier stage where they functioned well while they take nilotinib. Take them off it and they regress.”

In fact, Bennett is so excited by the treatment that he is hoping more patients seek him out so he can prove the treatment is effective. He said the effects take about four months to see improvements.

Madeline Carano has been taking the drug for about one month. Don Carano said he not only had to find a doctor who would prescribe nilotinib, he had to find a pharmacy that would fill the prescription as an off-use drug. The retired businessman so believes he will help his wife he has framed the prescription from Bennett.

“I was in financial services for 42 years and I have the resources to afford this, and I am paying market price,” Carano said. “I think it is shameful that this is not being made available and that insurance companies are not willing to cover it.”

Bennett agrees.

“Why are they holding hostage a drug that could help millions of people?” said Bennett. “I think it's a battle over money, who will ultimately end up holding the patent for this. Georgetown, the Michael J. Fox Foundation and the insurance companies are controlling this.”

Carano said he searched the United States, Canada and England, looking for a doctor to work with before finding Bennett.

“All I heard was negatives,” Carano said. “Well, I did more research and asked doctors treating leukemia with the drug how many of their patients had dementia. The answer is none. I challenge doctors to look at that themselves.”

Carano has spoken to two of the people involved in the Georgetown University trial.

“One woman, 89, did not communicate and had been in bed for three years,” said Carano. “Within six months, she was out of bed, talking in sentences and knew her relatives again. A man, a former professor is out of his wheelchair. He reads, grills and even drives to the grocery store. Why would I not want this for my wife? I have been told there is a risk of sudden death, 5-6 percent. We are talking about elderly patients. People die. Why not try it? I do not believe this poses a significant risk or I would never have pursued it.”

Dr. Charbel Moussa, who directs Georgetown’s Laboratory of Dementia and Parkinson’s, conducted the preclinical research of nilotinib (Tasigna by Novartis), an FDA-approved drug for leukemia, assisted by Dr. Fernando Pagan, associate professor of neurology, who directs the movement disorders program at MedStar Georgetown University Hospital. In the press release, they reported that the drug improved cognition, motor skills and non-motor function in patients with Parkinson’s disease and Lewy body dementia and led to statistically significant and encouraging changes in toxic proteins linked to disease progression (biomarkers). The complete data was presented at Neuroscience 2015, the annual meeting of the Society for Neuroscience, in Chicago on Oct. 17, 2015.

“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,” Pagan said. “But it is critical to conduct larger and more comprehensive studies before determining the drug’s true impact.”

Investigators reported that the six-month, dose-escalating study of nilotinib produced benefit for all study patients who completed the trial (11 of 12), with 10 patients reporting meaningful clinical improvements. Patients also showed positive changes in relevant cerebrospinal fluid biomarkers of Parkinson’s.

The researchers say the nilotinib trial was not compared to a control group, nor was it compared with a placebo or other medications used to treat Parkinson’s in the study. However, the researchers said that during nilotinib use 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. Researchers say that use of nilotinib, in doses much smaller than are used to treat cancer (which is up to 800 milligrams daily), was well tolerated with no serious side effects. In addition, researchers found that the drug penetrates the blood-brain barrier in amounts greater than dopamine drugs.

But the observed efficacy in cognition, motor skills and non-motor function improvement (such as constipation) for many patients was the most dramatic result, Pagan said. The investigators report that one individual who was using a wheelchair was able to walk again; three others who could not talk were able to hold conversations.

“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,” Pagan says.

According to the release, Alan Hoffman, Ph.D., a retired professor of social science education at Georgia State University, was diagnosed with Parkinson’s disease in 1997 and has participated in several clinical trials with no benefit, he says, until he enrolled in Pagan’s study.

“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,” he says.

In the three weeks before enrolling in the study, Hoffman says he fell eight times, but 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 said. “To say that nilotinib has made a change in our lives is a huge understatement.”

Moussa and other Georgetown researchers are now planning larger clinical trials with nilotinib for patients with Parkinson’s and other similar diseases including Alzheimer’s disease.

Representatives from the Michael J. Fox Foundation for Parkinson’s Research approached GU about helping to fund the continued research. Disputes between the two groups have stalled trials and the MJF Foundation staff members say they will conduct their own trials.

According to Novartis, the cost of nilotinib for the treatment of CML is about $10,360 a month for 800 milligrams daily. The dose used in this study was 150 and 300 milligrams daily.

Pagan reported having no personal financial interests related to the study. The phase I study received philanthropic funding and was supported by the Georgetown-Howard Universities Center for Clinical and Translational Science.

“How can you be a doctor, know what this drug can do and never write another prescription?”’ said Carano. “My wife was never sick, until this, and raised six children. She was a beautiful woman and she will be again. I want to get her back. Muhammad Ali was a world treasure. I believe this could have been used and he would still be here. Every day we delay this treatment hurts so many more people.”

Carano and Bennett have agreed to allow the progress of his wife to be followed and they believe there will be positive outcomes to report, beginning in a few months.

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