From Silicon Investor; leukemia drugs tested for halting accumulations of proteins in brains
Cancer Drug Prevents Build-up of Toxic Brain Protein
Published: May 10, 2013. by Georgetown University Medical Center
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.
• External link to Georgetown University Medical Center
• More news from Georgetown University Medical Center
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 malfunct
That's interesting, but it does seem like a rather blunt and indirect approach. I'd prefer to target the underlying reason that the proteins are accumulating in the first place. If the metal imbalance is causing the proteins to clump and form plaques, target the metal imbalance.
While I hope every attempt to treat these ND diseases succeeds, this seems like a 'throw it against the wall and see if it sticks' attempt. You have a known drug with known safety profile, so let's find some other applications for it. Interesting, but I wouldn't bet the farm on it. PBT2 on the other hand is the product of several decades of basic research into the mechanism of AD development.
Maybe as the years go by, we'll find that a combination of drugs are used to treat AD and other ND diseases. An initial course of treatment to clear away the plaques if needed, PBT2 to keep the AB from forming plaques again, and drugs to slow down the production of AB in the first place. But for right now, I'd be thrilled if PBT2 showed some impressive results.