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Esther Heerema, MSW

Cancer Drug Reverses Alzheimer’s Symptoms and Decreases Amyloid Beta in Mice

By February 9, 2012

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A drug approved for treatment of skin cancer has been shown to rapidly reverse signs and symptoms of Alzheimer's disease in mice.

Researchers at Case Western Reserve University School of Medicine demonstrated that bexarotene (brand name Targretin) decreased the presence of amyloid beta, the protein that becomes out of control and forms plaque in the brain as Alzheimer's progresses. Bexarotene is approximately 10 years old and is an FDA approved drug for cutaneous T-cell lymphoma.

Levels of amyloid beta protein present in the brain responded quickly to the drug, decreasing notably within 24 hours, and by 75% after two weeks.

Even more importantly, the mice displayed a reversal of the cognitive problems they had exhibited, such as memory problems and impaired social behavior.

The spatial memory of mice was tested by observing their navigation through a maze. Their ability to construct a nest, which requires cognition but also social interaction, improved dramatically. Researchers also noted that the mice's memory for smells improved with the treatment. (As humans, our ability to detect or distinguish between odors often deteriorates as Alzheimer's progresses.) All areas showed notable improvement after just nine days of treatment with bexarotene.

Finally, the study demonstrated effectiveness in both early and later stages of Alzheimer's in the mice. This is important because most medications currently approved to treat Alzheimer's are helpful only in the early stages of the disease.

This drug is clearly effective in mice. What remains to be seen, but is surely hoped for, is its affect on people. Since the medication is already approved by the FDA, it is anticipated that clinical trials in humans will be able to occur relatively soon.

This study was published in the online journal Science.

Comments
February 10, 2012 at 1:20 pm
(1) James Michael Howard says:

Bexarotene may exert Beneficial Effects of Reducing Beta-Amyloid by Increasing Testosterone (James Michael Howard, Fayetteville, Arkansas)

(Science 2012: “ApoE-Directed Therapeutics Rapidly Clear beta-Amyloid and Reverse Deficits in AD Mouse Models,” Cramer, et al., report that “…RXR [retinoid X receptor] activation [by bexarotene] stimulates physiological Aß [beta-amyloid] clearance mechanisms, resulting in the very rapid reversal of a broad range of Aß-induced deficits.”

Bexarotene is a “retinoid x receptor agonist.” Research suggests that stimulation of estradiol and testosterone may involve “retinoid X receptor signaling.” (Endocrinology. 2009 Sep;150(9):4260-9). I could not find any research connecting bexarotene with estradiol or testosterone.

Low testosterone and estradiol have been found in Alzheimer’s disease and have been identified as potential sources of Alzheimer’s disease. Moreover, testosterone and estrogen have been found to reduce beta-amyloid formation (Front Neuroendocrinol. 2009 Jul;30(2):239-58).

I suggest the positive effects that bexarotene produces in reducing beta-amyloid in mice may be due to increases primarily in testosterone and estradiol. Research supports reduced beta-amyloid accumulation in mice caused more bytestosterone than estradiol(Brain Res. 2010 Nov 4;1359:281-90). Alzheimer’s occurs more in women than men.

It is my hypothesis of 1985 that low DHEA may be the cause of Alzheimer’s disease. I think the evolutionary function of the sex hormones is induction of cellular receptors which participate in the absorption and use of DHEA for cellular function. There are indications that DHEA produces positive actions against the effects of beta-amyloid neurotoxicity (Neuropsychiatr Dis Treat. 2008 Feb;4(1):209-18). I could not find any research connecting bexarotene with DHEA.)

February 13, 2012 at 2:25 pm
(2) MIKE says:

Great news,

How do I get some of this for my mom?

February 13, 2012 at 2:44 pm
(3) Esther Heerema says:

Hi Mike,

Thanks for asking. Below is a direct quote from the Alzheimer’s Research Laboratory at Case Western Reserve University School of Medicine where this exciting research was conducted.

“Thank you for your interest in our work, we are touched you have reached out to the Alzheimer’s Research Laboratory. We are excited about our findings, and are hopeful that the work we have done in mice will translate to an effective treatment for those with Alzheimer’s disease. It is very early in the process, and while we are not currently enrolling patients in clinical trials, it is probable that any subsequent clinical trial will be carried out through NIH-sponsored Alzheimer’s Disease Research Centers. For those interested in clinical research today, our recommendation is to connect with the Alzheimer’s Association website, as they have a program in place for connecting people with clinical trials. Here is the link:

http://www.alz.org/research/clinical_trials/find_clinical_trials_trialmatch.asp

Again, our best to you from everyone here at the Alzheimer’s Lab at Case Western Reserve University School of Medicine.”

—Esther here now- I would definitely recommend staying connected to the Alzheimer’s Association website. Their link is very helpful in finding clinical trials.

Also, if I hear anything about the launch of clinical trials for this medication, I will definitely write about it here on this website so you and others can be aware.

All the best to you and your mom.

February 14, 2012 at 12:46 pm
(4) Kaleem says:

Dear Esther,
Great to read this article. Is this drug currently available in any country to be used for dementia- if not- how much time it may take to come to the market for this purpose.

February 14, 2012 at 4:49 pm
(5) Esther Heerema says:

Kaleem,

I would assume (but I can’t say for certain) it’s not available in any other country yet with the purpose of treating dementia since this research is so recent. It needs to be proven effective and safe for humans.

Thanks for checking!
-Esther

February 26, 2012 at 12:20 am
(6) Dr Billy levin says:

The skin and the brain are of common origin from the Ectodermal layer of the developing embryo. Many conditions of brain and skin are linked. ADHD and skin allergies occur together. Antibiotics from the “Terramycin” family used in Acne will have a dramatic effect on brain conditions like injury and anoxia. If it helps the skin, it can help the brain.
Thus it is just possible that a product that helps skin cancer might also help Altzheimers. Vasopressin for Diabetes Insipidus helps Memory. Minomicin prevents brain damage in anoxic births.

June 6, 2012 at 10:50 pm
(7) jennifer says:

The researchers from the Case Western Reserve University in Cleveland, Ohio found that when the mice exhibiting Alzheimer’s symptoms were administered bexarotene, they became smarter almost instantly, and not only did they perform better in tests, but also showed memory retention as well as improved social behavior. studies showed that if the drug worked out to the mice why not on human beings, so the neuroscientists goes with millions of testings for the drug because of it’s side effect.

October 14, 2013 at 8:00 pm
(8) Bill G. says:

Unfortunately the repurposing of drugs already found to be safe for use in humans is painfully slow. While faster then starting from scratch, initial trial information is often abandoned, and trial updates are preformed specifically for any new application. It is this strict adherence to clinical’s that slows the process dramatically.
There is certainly human trial evidence that already in exists.
If oncologists would correlate data from patients who have used bexarotene for the treatment of skin cancer, and also had a secondary diagnosis of Alzheimer’s, any adverse side effects should already documented within their notes.
My point is, that there already exists a wealth of information regarding clinical use of bexarotene, hidden within treatment records that are currently inaccessible.
It is exactly this type of information, hidden within practitioners records, that might speed along the repurposing of promising medications that could ease the suffering of millions, and those that care for them.

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