A drug that's already approved for treating leukemia appears to dramatically reduce symptoms in people who have Parkinson's disease with dementia, or a related condition called Lewy body dementia.
A pilot study of 12 patients given small doses of nilotinib found that movement and mental function improved in all of the 11 people who completed the six-month trial, researchers reported Saturday at the Society for Neuroscience meeting in Chicago.
And for several patients the improvements were dramatic, says Fernando Pagan, an author of the study and director of the Movement Disorders Program at Georgetown University Medical Center. One woman regained the ability to feed herself, one man was able to stop using a walker, and three previously nonverbal patients began speaking again, Pagan says.
"After 25 years in Parkinson's disease research, this is the most excited I've ever been," Pagan says.
If the drug's effectiveness is confirmed in larger, placebo-controlled studies, nilotinib could become the first treatment to interrupt a process that kills brain cells in Parkinson's and other neurodegenerative diseases, including Alzheimer's.
One of the patients in the pilot study was Alan Hoffman, 74, who lives with his wife, Nancy, in Northern Virginia.
Hoffman was diagnosed with Parkinson's in 1997. At first, he had trouble moving his arms. Over time, walking became more difficult and his speech became slurred. And by 2007, the disease had begun to affect his thinking.
"I knew I'd dropped off in my ability to read," Hoffman says. "People would keep giving me books and I'd have read the first chapter of about 10 of them. I had no ability to focus on it."
"He had more and more difficulty making sense," Nancy Hoffman says. He also became less active, less able to have conversations, and eventually stopped doing even household chores, she says.
But after a few weeks on nilotinib, Hoffman "improved in every way," his wife says. "He began loading the dishwasher, loading the clothes in the dryer, things he had not done in a long time."
Even more surprising, Hoffman's scores on cognitive tests began to improve. At home, Nancy Hoffman says her husband was making sense again and regained his ability to focus. "He actually read the David McCullough book on the Wright brothers and started reading the paper from beginning to end," she says.
The idea of using nilotinib to treat people like Alan Hoffman came from Charbel Moussa, an assistant professor of neurology at Georgetown University and an author of the study.
Moussa knew that in people who have Parkinson's disease with dementia or a related condition called Lewy body dementia, toxic proteins build up in certain brain cells, eventually killing them. Moussa thought nilotinib might be able to reverse this process.
His reasoning was that nilotinib activates a system in cells that works like a garbage disposal — it clears out unwanted proteins. Also, Moussa had shown that while cancer cells tend to die when exposed to nilotinib, brain cells actually become healthier.
So Moussa had his lab try the drug on brain cells in a petri dish. "And we found that, surprisingly, with a very little amount of the drug we can clear all these proteins that are supposed to be neurotoxic," he says.
Next, Moussa had his team give the drug to transgenic mice that were almost completely paralyzed from Parkinson's disease. The treatment "rescued" the animals, he says, allowing them to move almost as well as healthy mice.
Moussa's mice got the attention of Pagan from Georgetown's Movement Disorders Program. "When Dr. Moussa showed them to me," Pagan says, "it looked like, hey, this is type of drug that we've been looking for because it goes to the root of the problem."
The pilot study was designed to determine whether nilotinib was safe for Parkinson's patients and to determine how much drug from the capsules they were taking was reaching their brains. "But we also saw efficacy, which is really unheard of in a safety study," Pagan says.
The study found that levels of toxic proteins in blood and spinal fluid decreased once patients began taking nilotinib. Also, tests showed that the symptoms of Parkinson's including tremor and "freezing" decreased. And during the study patients were able to use lower doses of Parkinson's drugs, suggesting that the brain cells that produce dopamine were working better.
But there are some caveats, Pagan says. For one thing, the study was small, not designed to measure effectiveness, and included no patients taking a placebo.
Also, nilotinib is very expensive. The cost of providing it to leukemia patients is thousands of dollars a month.
And finally, Parkinson's and dementia patients would have to keep taking nilotinib indefinitely or their symptoms would continue to get worse.
Alan Hoffman was OK for about three weeks after the study ended and he stopped taking the drug. Since then, "There's (been) a pretty big change," his wife says. "He does have more problems with his speech, and he has more problems with cognition and more problems with mobility."
The Hoffmans hope to get more nilotinib from the drug's maker, Novartis, through a special program for people who improve during experiments like this one.
Meanwhile, the Georgetown team plans to try nilotinib in patients with another brain disease that involves toxic proteins: Alzheimer's.
DAVID GREENE, HOST:
Now a small study with potentially big implications. The study was presented over the weekend at the Society for Neuroscience meeting in Chicago, and it has people who work with Parkinson's very excited. A cancer drug appears to help patients with Parkinson's and also a related form of dementia. NPR's Jon Hamilton reports on the preliminary but pretty dramatic results.
JON HAMILTON, BYLINE: In people with Parkinson's disease, toxic proteins build up in certain brain cells, eventually killing those neurons. Several years ago, a researcher named Charbel Moussa at Georgetown University Medical Center got an idea. He thought a drug already approved for cancer might be able to reverse this buildup of toxins in brain cells. Moussa says the drug activates a system in cells that works like a garbage disposal. It clears out unwanted proteins.
CHARBEL MOUSSA: And we found that surprisingly with a very little amount of the drug, we can clear all these proteins that are supposed to be neurotoxic.
HAMILTON: But that was in cells growing in petri dishes. So Moussa had his team try the drug on transgenic mice that developed Parkinson's disease.
MOUSSA: When we tested the transgenic mice for behavioral outcomes, we saw that the mice, which were almost completely paralyzed, they were rescued.
HAMILTON: They were moving like healthy mice again. That got the attention of Fernando Pagan, the neurologist in charge of Georgetown's Movement Disorders Program.
FERNANDO PAGAN: When I saw these mice when Dr. Moussa showed them to me, it looked like, hey, this is the type of drug that we've been looking for because it goes to the root of the problem.
HAMILTON: The drug is nilotinib, a new and very costly treatment for leukemia. Nilotinib kills cancer cells, but brain cells thrive on low doses of the drug. Pagan wondered whether nilotinib would be safe for patients with Parkinson's and a form of dementia that often accompanies the disease. So for six months, he gave tiny amounts of the drug to a dozen patients, including this man.
ALAN HOFFMAN: I'm Alan Hoffman, and I'm 64 years old - 74. And I have a Ph.D. from Michigan State University in social science education - taught there for 27 years.
HAMILTON: Now Hoffman lives in northern Virginia with his wife, Nancy. He was diagnosed with Parkinson's in 1997. By 2007, the disease had begun to affect his thinking. Nancy Hoffman says things got really bad during a trip to London.
NANCY HOFFMAN: He had more and more difficulty making sense, and he was being pretty belligerent. And I said something to him that I later cried my eyes out over doing, but I said, Alan, you have dementia.
HAMILTON: That was something Alan already suspected.
A. HOFFMAN: I knew I had dropped off. You know, people would keep giving me books and I'd have read the first chapter of about 10 of them. I had no ability to focus on it.
HAMILTON: The Hoffman's tried experimental drugs and deep brain stimulation. The treatments helped, but didn't halt the disease. Eventually, the couple came to Fernando Pagan at Georgetown, and he offered Alan a chance to enroll in the study of nilotinib. Pagan shows me a video taken at the beginning of the study. Alan is walking down a corridor as part of a timed test.
PAGAN: You can see he's slow. There's a decreased arm swing there on the right. He's a little bit wobbly when he walks.
HAMILTON: And his posture is twisted by a muscle problem called dystonia. Next, Pagan shows a video of Hoffman taking the same test after two months on nilotinib.
PAGAN: Here, he went from 15 seconds originally to eight seconds - much straighter, less dystonia and no longer using a cane.
HAMILTON: Alan Hoffman remembers that day.
A. HOFFMAN: That was a shock to everybody. I mean, I didn't expect to do it. And I was walking like a normal human being.
HAMILTON: Even more surprising, Hoffman's scores on cognitive tests began to improve. The study ended in August, but Nancy Hoffman remembers that while her husband was on the drug he did things he hadn't done in years.
N. HOFFMAN: He actually read the David McCullough book on the Wright brothers and started reading the paper from beginning to end.
HAMILTON: Pagan says everyone in the study improved, though the amount varied. Levels of toxic proteins in their blood and spinal fluid decreased, and they were able to function on lower doses of Parkinson's drugs. After the study ended, Alan Hoffman says he was OK for about three weeks.
A. HOFFMAN: The last couple of weeks has been scary. I mean...
N. HOFFMAN: There's a pretty big change. He does have more problems with his speech and he has more problems with cognition and more problems with mobility.
HAMILTON: The Hoffmans hope to get more nilotinib through a program for people who improve during experiments like this one. Meanwhile, the Georgetown team plans to try nilotinib in patients with another brain disease that involves toxic proteins - Alzheimer's. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.