Skin-Cancer Drug Gives Preliminary Hope of Alzheimer's Treatment, Mouse Study Finds

PET Scan of Brain of a person with Alzheimer's with amyloid plaques showing loss of function in the temporal lobe (image courtesy of Wikipedia)A new study conducted on mice has found that a skin-cancer drug may give hope of providing a future effective treatment for Alzheimer’s dementia. The study found that the drug, bexarotene, successfully cleared away the amyloid plaques in the brain that are characteristic of Alzheimer’s, and reversed the cognitive and other neural decline that accompanied the amyloid plaques in the brains of the mice.

The new study, by Dr. Paige E. Cramer of the Department of Neurosciences, Case Western Reserve University School of Medicine in Cleveland, Ohio and colleagues, was published on February 9, 2012 in the journal Science.

Demonstrating the urgent need for an effective treatment for Alzheimer’s as our population ages, the Wall Street Journal and other news sources report that since publication of the study, there already has been a clamor of thousands of families afflicted with Alzheimer’s seeking access to the skin-cancer drug, even though scientists caution that the drug has not yet been tested or approved for use in treatment of Alzheimer’s in humans.

Alzheimer’s Spread and its Characteristics

According to the 2011 Alzheimer’s Disease Facts and Figures, published by the Alzheimer’s Association, 5.4 million Americans are now living with Alzheimer’s and 15 million Americans are caring for someone with Alzheimer’s, numbers that are growing in epidemic proportions as our population ages. Every 69 seconds someone in the U.S. now develops Alzheimer’s, which is the 6th leading cause of death in the U.S., and the only one among the top 10 causes of death that cannot yet be prevented, cured or even slowed, the Alzheimer’s Association reports. Drugs currently approved for treatment of Alzheimer’s may temporarily slow the progression of memory loss and loss of functions in some people, but none of these medications cures or halts the disease.

As explained by the authors of the new study, “Alzheimer’s disease is associated with impaired clearance of β-amyloid from the brain, a process normally facilitated by [the gene] apolipoprotein E (ApoE).” That is, people who do not suffer from Alzheimer’s appear to have a gene (ApoE) that normally clears away the B-amyloid protein plaque, which builds up in the brains of those for whom the ApoE gene may not be functioning.

The New Study Findings

In the new study, the researchers administered oral doses of the skin-cancer drug bexarotene to mice bred to have amyloid plaques in the brain, characteristic of Alzheimer’s.

Surprisingly, this resulted in an immediate clearing of the amyloid plaques from the brains of the mice, within hours. The researchers found that the “Aβ plaque area was reduced >50% [more than 50%] within just 72 hours.”

“Furthermore,” the researchers reported, “bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function.”

As to how bexarotene may act in this way, the scientists noted that the gene ApoE which appears to clear away the plaques is activated by certain receptors, including a “retinoid X receptor (RXR),” and that bexarotene activates RXR. The authors wrote,

“ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator activated receptor (PPARγ) and liver X receptors (LXR) in coordination with retinoid X receptors (RXR). Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the very rapid reversal of a broad range of Aβ-induced deficits. Oral administration of the RXR agonist, bexarotene, to a murine [in mice] model of Alzheimer’s disease resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner.”

Implications

While this study in mice gives preliminary hope of a future treatment for Alzheimer’s, scientists and doctors stress that it is premature to conclude that bexarotene would be safe or effective as a treatment of Alzheimer’s in humans.

Even though bexarotene could legally be prescribed by doctors “off-label” for Alzheimer’s treatment, because it has already been approved by the U.S. Food and Drug Administration for skin cancer, Alzheimer’s experts urge patients and families to wait until the drug is proved safe and effective for Alzheimer’s by years of clinical trials.

“At this point in time, it would really be unethical for a physician to prescribe the medication and, I think, foolish for the patient to take it,” William Thies, chief medical and scientific officer for the Alzheimer’s Association, told ABC News.

The National Institutes of Health warns that, like other cancer drugs, bexarotene can produce serious side effects in humans, including headaches, hair loss, nausea and depression, as well as increased cholesterol levels and increased triglycerides. Bexarotene may also produce other adverse reactions if combined with other medications, many of which are commonly taken by Alzheimer’s patients.

Other physicians suggest that perhaps the research and regulatory process will move faster for bexarotene’s potential use for Alzheimer’s patients, because the drug already has been approved for other uses.

“[W]e may anticipate that successful studies will translate into a demand for accelerated drug approval as the process moves forward since so much is at stake in the quest for a treatment and cure,” writes Dr. Dan Gold, a board-certified family physician, in an article published in the Great Falls Tribune.

“If this drug is the answer to Alzheimer’s dementia, its discovery eventually could be hailed as one of the foremost medical discoveries of the new century.”

More Information

See related HelpingYouCare™ reports on:

Nearly 15 Million Americans Are Now Caring for Someone With Alzheimer’s Disease – A Number Rapidly Growing

Obama Administration Increases Funding for Alzheimer’s Research & Caregiver Support

Alzheimer’s Spreads in the Brain like a Virus, New Study Finds

Fruits, Vegetables & Fish May Keep Brain from Shrinking, New Study Finds

Regular Exercise Slows Mental Decline With Aging, Studies Find; May Make You Cognitively Younger by 5 to 7 Years

Half of Alzheimer’s Cases Attributable to 7 Risk Factors Preventable by Lifestyle Changes, Study Finds

For more information on Alzheimer’s and dementia, see the HelpingYouCare™ resource pages on Alzheimer’s/ Dementia, including:

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Copyright © 2012 Care-Help LLC, publisher of HelpingYouCare™.

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