Bexarotene for Alzheimer’s Disease?

Posted by Mark Abramowicz, M.D.

A startling article in the March 23rd issue of Science reported that, in a mouse model of human Alzheimer’s disease, the oral retinoid analog bexarotene (Targretin) reduced beta-amyloid plaques by more than 50% within 72 hours and rapidly reversed the cognitive, social and olfactory deficits of the mice.

Bexarotene has been marketed in the US since 2000 for treatment of cutaneous T-cell lymphoma. Its main adverse effects have been hyperlipidemia and hypothyroidism, both of which are treatable with other drugs. More serious toxicities such as hepatitis and pancreatitis have occurred uncommonly.

Bexarotene has a mechanism of action that makes it a plausible candidate for treatment of Alzheimer’s: retinoid X receptors are involved in the normal clearance of beta-amyloid, which is impaired in these patients.

FDA-approved treatments for Alzheimer’s (4 acetylcholinesterase inhibitors and the NMDA receptor-antagonist memantine), last reviewed in Treatment Guidelines from The Medical Letter in 2010, have had only marginal clinical effects, and none have slowed, let alone reversed, the neurodegenerative process.

The authors of the article in Science called for the initiation of controlled trials, which undoubtedly will be done, but we probably will not have to wait long for some preliminary reports of bexarotene’s use in humans with Alzheimer’s disease.

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