Cancer drug might fight Alzheimer's - Biomedicine - imatinib mesylate, or Gleevec - Brief Article

Science News, Nov 1, 2003

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. 1 Proceedings of the National Academy of Sciences, researchers report that experiments on cultured rat brain ceils 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 bloodbrain 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.--N.S.