A drug for leukemia and colon cancer might also inhibit the formation of the waxy plaques found in the brains of people with Alzheimer’s disease, a study of animals shows. The drug, imatinib mesylate, which is marketed as Gleevec, is an enzyme suppressor.
In the Oct. 14 Proceedings of the National Academy of Sciences, researchers report that experiments on cultured rat brain cells show that the drug reduces the formation of the peptide called amyloid-beta, which typically forms into the plaques. The drug works by hampering the activity of gamma secretase, an enzyme that cleaves a precursor compound to form amyloid-beta peptide.
When dripped into guinea pigs’ spinal fluid via a small pump implanted under each animal’s skin, imatinib mesylate suppressed the formation of amyloid-beta-peptide plaques in the guinea pigs’ brains, says William J. Netzer of Rockefeller University in New York. The spinal drip was necessary because imatinib mesylate doesn’t pass through the blood-brain barrier. Doctors might someday deliver the drug this way as a treatment for Alzheimer’s disease, Netzer says. Or scientists could develop a version that permeates the blood-brain barrier.
In the animal studies, imatinib mesylate slowed plaque formation without inhibiting gamma secretase’s cleavage of a protein known as Notch. Notch plays a key role in brain and immune system development, but only when cut by an enzyme. Other gamma secretase inhibitors have thwarted Notch cleavage, diminishing their prospects as anti-Alzheimer’s drugs.
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