Researchers at Case Western University have found that an FDA approved cancer drug, bexarotene, appears to reverse Alzheimer’s symptoms in mice by removing the buildup of amyloid plaque in the brain. The research holds the promise of a significant breakthrough in finding a better treatment for Alzheimer’s disease which affects about 5.4 million Americans.
The study drug bexarotene has been used in the treatment of certain cancers for more than a decade and has a good safety and side-effect profile, which researchers hope will help speed the transition to clinical trials of the drug for Alzheimer’s.
How the Drug Works
One of the hallmarks of Alzheimer’s disease is the buildup of “sticky” protein pieces called beta-amyloid into clumps called plaques. These plaques accumulate around nerve cells which blocks cell signaling at nerve synapses and damage the cell itself. They may also activate immune system cells that respond by attacking and devouring damaged cells.
The body's inability to clear amyloid beta from the brain is a major factor in the development of Alzheimer's disease. Previous research showed that the main cholesterol carrier in the brain, apolipoprotein E (ApeE), plays an important role in clearing amyloid beta proteins.
In this study, the researchers found that bexarotene increased ApoE expression, and the elevated levels of ApoE increase clearance of amyloid beta from the brain. Bexarotene stimulates retinoid X receptors (RXR), which are proteins that control the production of ApoE.
Within six hours of receiving bexarotene, soluble amyloid levels in the mice fell by 25 percent and the effect lasted for three days. This decrease was associated with rapid improvement in a wide number of behaviors in mice with Alzheimer's.
In addition, bexarotene treatment also rapidly stimulated the removal of amyloid plaques from the brain, the researchers said.
More Research Needed
While the promise of a therapy for Alzheimer's disease is exciting, senior author of the study Gary Landreth, PhD expressed cautious optimism, "We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans. We are at an early state in translating this basic science discovery into a treatment." Let’s all keep our fingers crossed!
Learn more about Case Western’s research and the study findings in this video.
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