Researchers from the University of Pittsburgh Graduate School of Public Health have discovered that an anti-cancer drug reverses Alzheimer’s disease deficits in mice.
The researchers examined previously published studies on the drug bexarotene, which is approved by the FDA for the treatment of cutaneous T cell lymphoma.
The researchers were able to confirm that bexarotene does notably improve cognitive shortcomings in mice expressing gene mutations associated with Alzheimer’s disease, but could not verify the effect on amyloid plaques.
According to the Newsletter of the Memory Disorders Project at Rutgers University, amyloid plaques are sticky buildup which collects outside nerve cells, or neurons. Amyloid plaques are thought to cause the associated memory deficits of Alzheimer’s disease.
Senior author Rada Koldamova, an associate professor in the Pitt Public Health’s Department of Environmental and Occupational Health, said that the researchers think these findings suggest that additional research into bexarotene as a treatment for Alzheimer’s disease is warranted.
Dr. Koldamova and her team were examining mice expressing human Apolipoprotein E4 (APOE4), when a group of a researchers published a study revealing that bexarotene bettered memory and quickly got rid of amyloid plaques from the brains of Alzheimer’s model mice expressing mouse Apolipoprotein E (APOE).
Bexarotene is a compound that mobilizes Retinoic X Receptors (RXR) located throughout the body, including neurons and other brain cells. Once prompted, the receptors bind to DNA and manage the expression of genes that direct numerous biological processes. Higher levels of APOE are one result of RXR activation by bexarotene.
According to co-author Iliya Lefterov, an associate professor in Pitt Public Health’s Department of Environmental and Occupational Health, the researchers were already prepared to repeat the published study to figure out whether they could independently confirm its findings.
While they were not able to locate any evidence that the bexarotene removed the plaques from the brains of Alzheimer’s model mice, they were able to confirm that the mice rapidly regained their lost cognitive skills.
The researchers believe that the drug workers through a different biological process, perhaps by reducing soluble oligomers which are made up of the toxic amyloid beta protein fragments. However, the oligomers are made up of smaller amounts of amyloid beta and are still able to “move.”
“We did find a significant decrease in soluble oligomers,” said Dr. Koldamova in a statement. “It is possible that the oligomers are more dangerous than the plaques in people with Alzheimer’s disease. It also is possible that the improvement of cognitive skills in mice treated with bexarotene is unrelated to amyloid beta and the drug works through a completely different, unknown mechanism.”
According to a news release from the University of Pittsburgh Graduate School of Public Health, mice with the Alzheimer’s gene mutations expressing human APOE3 or APOE4 were able to do as well in cognitive tests as their non-Alzheimer’s peers ten days after starting treatment with the anti-cancer drug.
The study’s findings are described in detail in the journal Science.