Attempts to reproduce results did not use proper formulation, researchers say
A preliminary report from scientists at the biotech company Amgen Inc. questions a cancer drug’s ability to fight Alzheimer’s disease. In experiments described February 4 in F1000Research, bexarotene, a drug approved by the FDA to treat lymphoma, didn’t reduce levels of the Alzheimer’s-related amyloid-beta protein.
In the original work, described in Science in 2012 (SN: 3/10/12, p. 5), neuroscientist Gary Landreth of Case Western Reserve University in Cleveland and colleagues showed that bexarotene swiftly clears A-beta from the brains of mice, reducing both the sticky plaques and smaller forms of the protein that circulate in the brain. The mice also showed signs of improved learning and memory. A year after that work appeared, four reports, also in Science, disputed some of those findings.
In tests on rats, the Amgen scientists found that bexarotene didn’t drop levels of plaques or smaller forms of A-beta. The new study didn’t describe behavioral tests. Landreth points out that this study, and previous experiments that failed to find a benefit, used a formulation of the drug that wouldn’t persist at high enough levels in the brain to be useful.
“The controversy with the preclinical data is going to go away in the face of solid clinical trials,” Landreth says. A small clinical trial published online January 29 in Alzheimer’s Research & Therapy found that bexarotene reduced A-beta in the brains of people, but only people without a particular version of the ApoE gene, a known risk factor for Alzheimer’s.
Larger trials would be more informative, says Landreth, who stands by his group’s original findings. “When we published our Science paper, it took us five years and we did the best science we could,” Landreth says. “And I am convinced that we are right.”
S. Wang, P. Wen and S. Wood. Effect of LXR/RXR agonism on brain and CSF Aβ40 levels in rats [version 1; referees: awaiting peer review]. F1000 Research. Published online February 4, 2016. doi: 10.12688/f1000research.7868.1
J. Cummings et al. Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer’s disease. Alzheimer’s Research & Therapy. Published online January 29, 2016. doi: 10.1186/s13195-016-0173-2
L. Sanders. Cancer drug may have Alzheimer’s benefits. Science News. Vol. 181, March 10, 2012, p. 5.