Alzheimer’s disease may have met its match.
Neuroscientists at Case Western Reserve University School of Medicine in Cleveland are reporting a huge breakthrough in the effort of finding a cure for Alzheimer's, their findings published in the journal Science.
According to the Case Western researchers, using the cancer treatment drug Bexarotene on mice appears to quickly reverse the pathological, cognitive and memory deficits caused by the onset of Alzheimer's. Bexarotene has been approved for the treatment of cancer by the U.S. Food and Drug Administration for more than a decade.
Alzheimer's occurs in large part from the body's inability to clear amyloid beta protein from the brain, researchers said. In 2008, Case Western researcher Gary Landreth, PhD, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins.
In this new study, Landreth and his colleagues chose to explore the effectiveness of bexarotene for increasing ApoE expression. The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain.
In particular, the researchers were struck by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of Alzheimer's disease. The treatment correlated with rapid improvement in a broad range of behaviors in three different mouse models of Alzheimer's.
Landreth did stress that despite the exciting nature of the results, the treatment has not yet been tested in humans. “Our next objective is to ascertain if it acts similarly in humans,” he said. “We are at an early stage in translating this basic science discovery into a treatment."
The mouse models did prove effective, however. One example of the improved behaviors involved the typical nesting instinct of the mice. When mice with Alzheimer’s encountered material suited for nesting—in this study, tissue paper—they did nothing to create a space to nest. This reaction demonstrated that they had lost the ability to associate the tissue paper with the opportunity to nest.
Just 72 hours after the bexarotene treatment, however, the mice began to use the paper to make nests. Administration of the drug also improved the ability of the mice to sense and respond to odors.
Bexarotene treatment also worked quickly to stimulate the removal of amyloid plaques from the brain, researchers said.
Bexarotene has a “good safety and side-effect profile,” said the Case Western researchers, who also hope these attributes will help speed the transition to clinical trials of the drug.