The enzyme gamma secretase is a trickster. It can be found throughout the body and, depending on where it is or how it's used, can be a hero or a villain. Block the enzyme completely and you might end up developing cancer. But when gamma secretase is found in the brain, the enzyme is responsible for final production of amyloid beta. Those who follow Alzheimer's disease research will recognize amyloid beta as a leading culprit in the formation of plaques and in neuronal death. Researchers at Temple University think they've found a way to outsmart gamma secretase and reduce its amyloid beta production, yet not block the enzyme completely. And they've found it in a drug that's already on the market to treat asthma.
Writing in the American Journal of Pathology, the researchers describe how they use the drug Zileuton, which inhibits the enzyme 5-lipoxygenase to treat asthma. Turns out, though, that 5-lipoxygenase also controls the activation of that old enzyme enigma gamma secretase. In the study led by Temple associate professor Domenico Pratico, a transgenic mouse model of Alzheimer's disease was given Zileuton, resulting in a 50 percent reduction of gamma secretase's production of amyloid beta and buildup of amyloid plaques in the brain.
Pratico said in a release that Zileuton appears to be an ideal solution to the problem of controlling gamma secretase without actually blocking it since the drug only modulates the protein expression levels, which keeps some of its vital functions intact while blocking many of its bad effects. Pratico is also hopeful for a speedy approval process of this potential Alzheimer's treatment.
"This drug is already on the market and, most importantly, is already FDA-approved, so you don't need to go through an intense drug discovery process," Pratico said in a statement. "So we could quickly begin a clinical trial to determine if there is a new application for this drug against a disease where there is currently nothing."
- take a look at Temple University's release
- and learn more about the drug Zileuton
Special Report: Making sense of the Alzheimer's drug pipeline