Science: Mouse Studies Offer Alzheimer’s and Cancer Therapy Insights

Two mouse studies published this week suggest innovative approaches for treating two of the developed world’s most troubling diseases. One study tests a potential therapy using an FDA-approved cancer drug to treat Alzheimer’s, while the other examines how a few days of fasting may delay tumor growth and improve chemotherapy.

The first study, in the 9 February edition of Science Express, deals with the build-up of protein fragments called amyloid-beta, a key feature of Alzheimer’s disease. All human brains produce amyloid-beta, but in healthy individuals, enzymes break the fragments down with help from a protein called ApoE.

Paige Cramer of Case Western Reserve University School of Medicine and colleagues knew that a drug called bexarotene activates a protein that helps switch on the ApoE gene, and they hypothesized that the drug might therefore enhance the clearance of amyloid-beta in the brain. They gave the drug to mice engineered to have an Alzheimer’s-like condition and observed that levels of the amyloid-beta fragments in the mice’s brains dropped substantially within just a few days.

The mice also showed improvements in their cognitive and social behavior, as well as their sense of smell. Bexarotene, also known as Targretin, is currently approved by the U.S. Food and Drug Administration to treat a form of skin cancer.

 

Brain tissue from mice with an Alzheimerís-like disease, with amyloid-beta plaques stained red. The image on the left shows tissue from a mouse treated with a placebo; the image on the right shows tissue from a mouse treated with bexarotone for 14 days, displaying far fewer areas of amyloid plaque. [Image © Science/AAAS]

Brain tissue from mice with an Alzheimerís-like disease, with amyloid-beta plaques stained red. The image on the left shows tissue from a mouse treated with a placebo; the image on the right shows tissue from a mouse treated with bexarotone for 14 days, displaying far fewer areas of amyloid plaque.
[Image © Science/AAAS]

The second study, in the 8 February Science Translational Medicine, indicates that fasting prior to chemotherapy treatment may protect animals—and possibly humans—against the side effects of treatment.

 

Changhan Lee of the University of Southern California in Los Angeles and colleagues report that fasting for two days in the absence of other treatments can delay the progression of different types of cancer in mice. In some cases, fasting may be just as effective as toxic chemotherapy drugs at slowing down the tumors.

However, the combination of fasting and chemotherapy appears to be more effective than either alone at helping healthy cells resist damage from chemotherapeutic drugs. In fact, the researchers found that combined fasting and chemotherapy promoted long-term, cancer-free survival in up to 40% of mice with nerve tissue tumors called neuroblastomas.

 


Valter Longo discusses the effects fasting may have on healthy and cancerous cells during chemotherapy

[Video courtesy of Valter Longo, USC Davis School of Gerontology]

Although clinical trials testing the effects of fasting in cancer treatment are still in early stages, these studies suggest that fasting cycles have the potential to boost the efficacy of chemotherapy. The results are particularly relevant for advanced-stage patients for whom standard treatment is ineffective.

Links

Read the abstract, “ApoE-directed Therapeutics Rapidly Clear Beta-amyloid and Reverse Deficits in AD Mouse Models,” by Paige Cramer and colleagues.

Read the abstract, “Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy,” by Changhan Lee and colleagues.