Cancer Drug Prevents Build-up of Toxic Brain Protein in Parkinson's Mouse Model

Researchers at Georgetown University Medical Center have used tiny doses of a leukemia drug to halt accumulation of alpha-synuclein in the brains of mice. This finding provides the basis for clinical trials to study the effects in humans.

When nilotinib is used to treat chronic myelogenous leukemia (CML), it forces cancer cells into autophagy — a biological process that leads to death of tumor cells in cancer. This process is also considered important in clearing away toxic buildup of proteins like alpha-synuclein, the main protein that forms into Lewy bodies.

Using mice whose brains had been altered to resemble Parkinson’s disease, researchers studied the effects of the drug nilotinib. Treated mice showed improved clearance of toxic accumulation of alpha-synuclein from the inside of brain cells. The study also showed that movement and functionality in the treated mice was greatly improved, compared with untreated mice. Testing drugs in animal models of disorders like Parkinson’s and LBD is an important step in identifying compounds which later may be tried in humans.

"This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell,” said Charbel E-H Moussa, MB, PhD, the study’s senior investigator at Georgetown University. “By clearing intracellular proteins, the drug prevents their accumulation in pathological inclusions called Lewy bodies and/or tangles, and also prevents amyloid secretion into the extracellular space between neurons, so proteins do not form toxic clumps or plaques in the brain"

“This is an active area of research in neurodegenerative diseases and this new report offers promising preliminary data in animal models of Parkinson’s disease,” says John Duda, MD, a member of LBDA’s Scientific Advisory Council. “It is important to note that there is no guarantee it will be effective in humans, so more research is needed. For the time being, it would be premature to view nilotinib as a treatment option for dementia or movement disorders.

The research was published online May 10 in the journal Human Molecular Genetics. The study was supported by a National Institute of Health grant (NIA 30378) as well as Georgetown University funding. Moussa is listed on a provisional patent application to use nilotinib and bosutinib as a therapeutic approach in neurodegenerative diseases.