Leukemia drug nilotinib safe, shows promise against Alzheimer's disease

May 29 (UPI) -- The leukemia drug nilotinib, which shows promise in reducing the effects of Alzheimer's disease, is safe and has minimal side effects when used at low doses, according to a small clinical trial published Friday in the journal Annals of Neurology.

The drug, known commercially as Tasigna, appears to reverse some of the effects of Alzheimer's disease brain based on earlier research, the authors said.


"The results of this exploratory study repurposing nilotinib are encouraging," Howard Fillit, founding executive director and chief science officer at the Alzheimer's Drug Discovery Foundation, which funded the research, said in a statement.

Nearly 6 million Americans have Alzheimer's disease, a form of dementia, according to the Alzheimer's Association. No cure exists, although drug therapy might slow disease progression in some people.

Nilotinib was approved by the U.S. Food and Drug Administration to treat chronic myeloid leukemia, a slow-progressing cancer that typically strikes older adults, in 2007.


The study published Friday was a Phase II clinical trial -- the second step in the process to confirm the safety and effectiveness of experimental drugs and medical devices. Phase III trials, which have more participants, still are needed before the drug can be marketed as an approved treatment for Alzheimer's.

The rationale for studying nilotinib in Alzheimer's disease is based on laboratory and clinical research conducted by the Georgetown Translational Neurotherapeutics Program, according to the study authors.

This research found that nilotinib helps clear accumulated beta-amyloid plaques and Tau tangles in neurons in the brain -- both of which are signs of Alzheimer's, the authors said.

Nilotinib, which comes in capsule form, appears to penetrate the blood-brain barrier and turn on the "garbage disposal" machinery inside neurons -- called autophagy -- to get rid of the Tau, beta-amyloid and other toxic proteins, the researchers said.

For the new Phase II study, 37 people with mild dementia due to Alzheimer's were given either a placebo or nilotinib daily for 12 months. Those on nilotinib received 150 milligrams of the drug daily for 26 weeks, followed by a 300 mg daily dose for another 26 weeks.


In general, nilotinib was safe and well-tolerated, the researchers found, although some participants experienced mood swings -- agitation and irritation -- while on the 300 mg dose.

The drug carries an FDA "black-box warning" because of cardiovascular issues that might lead to sudden death in cancer patients -- who typically receive 600 mg daily -- but no such incidents were reported in this study.

"The increase in mood swings with 300 mg nilotinib is associated with dose-dependent increases of brain dopamine, suggesting that 150 mg nilotinib is the optimal dosage to investigate in a future Alzheimer study," Charbel Moussa, director of the Georgetown program, said in a statement.

Magnetic resonance imaging of study participants' brains also revealed that those treated with the drug experienced reduced beta-amyloid levels after both six and 12 months, with fewer Tau tangles in the spinal fluid.

"This is the first oral treatment found to lower amyloid burden in the brain," Dr. R. Scott Turner, director of Georgetown's Memory Disorders Program, said in a statement.

While this also has been found with several anti-amyloid antibodies, these treatments cannot be given orally. Phase III trials of the drug for Alzheimer's disease are being planned, Turner said.

"[Our] study found that [nilotinib] is safe and well-tolerated, as we anticipated, and that it may have disease-modifying benefits," he said.


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