Reversing Alzheimer’s symptoms in mice with axitinib treatment

Written by Ryan Gilroy (Future Science Group)

Alzheimer's and axitinib

Axitinib restored memory and cognitive function in mice that display symptoms of Alzheimer’s disease.

University of British Columbia (Canada) researchers demonstrated restoration of both memory and cognitive function in mice that display symptoms of Alzheimer’s disease by treatment with axitinib, a common chemotherapy drug.

“We are really very excited, because these findings suggest we can repurpose approved anti-cancer drugs for use as treatments for Alzheimer’s disease,” commented senior author Wilf Jefferies. “It could shorten the clinical development by years.”

Potential Alzheimer’s treatments have shown promise in animal models before but failed in clinical trials. Typically, these strategies target tau protein or the protein fragment beta-amyloid, but the researchers chose a different approach. They left the traditional targets alone and instead focused on preventing angiogenesis, a new target for Alzheimer’s therapies.

“Other than some controversial recent results, there’s been a paucity of success in these clinical trials. So, a great deal of effort appears to have been directed toward the wrong targets for reversing Alzheimer’s disease,” Jefferies observed.

Their previous work had shown that the proliferation of blood vessels compromises the blood-brain barrier in individuals with Alzheimer’s disease. Since cancerous tumors also rely on new blood vessel growth to survive and thrive, the researchers reasoned that a proven anticancer drug might halt the process in Alzheimer’s.

“Axitinib, the anti-cancer drug we used, blocks a receptor in the brain called a tyrosine kinase receptor, which is partly responsible for spurring blood vessel formation,” explained lead author Chaahat Singh. “It stops abnormal blood vessels from growing, which then prevents many downstream effects.”

By using axitinib for just one month, the researchers dramatically reduced blood vessel growth, restored the blood-brain barrier and most significantly, helped mice perform better on cognitive tests.

The treatment has only been applied to mice thus far. Clinical trials will be needed to assess the effectiveness of this treatment in humans with Alzheimer’s disease, as well as consideration for the long-term use of anticancer drugs in people living with Alzheimer’s, who are mostly elderly. If axitinib does work well in humans, repurposing an already-approved drug could more rapidly advance its use for Alzheimer’s.

“Researchers including myself have been disappointed in observing numerous clinical trials for Alzheimer’s disease fail to reach their clinical endpoints,” concluded Jefferies. “The therapeutic approach we discovered has an opportunity to revise the clinical treatment of Alzheimer’s patients, which I think is absolutely needed at this point for the field to advance.”