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February 13, 2012
Bexarotene for Alzheimer's
Here's another intriguing Alzheimer's result, in a field that could certainly use some. A group at Case Western (no, not the gyre guy) has reported on the effects of the RXR ligand Bexarotene (brand name Targretin) in several different mouse models of the disease. Dosing with the compound seems to quickly lower the levels of the soluble forms of beta-amyloid in the rodents' brains, most likely by increasing the expression of the lipoprotein ApoE. (That one's long been associated with Alzheimer's).
Update: a reader notes that Merck seems to have some interest in a related mechanism, using LXR to upregulate ApoE in Alzheimer's. And this upcoming Keystone Conference is sure to feature a lot of interesting discussion on the topic as well.
Follow-up showed that more than the soluble forms had been cleared, though. A significant amount of the insoluble amyloid plaques had been removed at long time points (several days), and the hypothesis there is some sort of immune reponse (an approach that's been tried for years now through vaccines, with very mixed success). Having a single drug (which has already been approved for some oncology indications) that appears to work rapidly on both the soluble and insoluble forms of amyloid is both dramatic and unexpected.
The Case Western group saw improvement on behavior and memory in the mice as well, as you might well hope. Since this drug has already been through the FDA, you'd hope that the way is clear to trying this same idea out in human patients. That, of course, is where many bright ideas in Alzheimer's have come to grief. If the drug doesn't affect ApoE expression in quite the same way, or if the lipoprotein doesn't act similarly in humans, or if that plaque-clearing mechanism, whatever it is, doesn't kick in or goes awry, then these results could end up just being another wonderful rodent study that didn't translate. But it's absolutely worth finding out, and I hope that we do in short order.
Update: this study is already triggering more interest in the Alzheimer's community than can be contained, which has been the story every time something promising shows up. . .
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