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Cancer drug prevents build-up of toxic brain protein
Date:5/9/2013

WASHINGTON Researchers at Georgetown University Medical Center have used tiny doses of a leukemia drug to halt accumulation of toxic proteins linked to Parkinson's disease in the brains of mice. This finding provides the basis to plan a clinical trial in humans to study the effects.

They say their study, published online May 10 in Human Molecular Genetics, offers a unique and exciting strategy to treat neurodegenerative diseases that feature abnormal buildup of proteins in Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington disease and Lewy body dementia, among others.

"This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell. 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," says the study's senior investigator, neuroscientist Charbel E-H Moussa, MB, PhD. Moussa heads the laboratory of dementia and Parkinsonism at Georgetown.

When the drug, 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.

"The doses used to treat CML are high enough that the drug pushes cells to chew up their own internal organelles, causing self-cannibalization and cell death," Moussa says. "We reasoned that small doses for these mice, an equivalent to one percent of the dose used in humans would turn on just enough autophagy in neurons that the cells would clear malfunctioning proteins, and nothing else."

Moussa, who has long sought a way to force neurons to clean up their garbage, came up with the idea of using cancer drugs that push autophagy in tumors to help diseased brains. "No one ha
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Contact: Karen Mallet
km463@georgetown.edu
Georgetown University Medical Center
Source:Eurekalert

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