Targeted cancer therapy reverses symptoms of Alzheimer’s disease in mice


A drug commonly used to treat cancer can restore memory and cognitive function in mice that show symptoms of Alzheimer’s disease, according to new research from UBC.

The drug, Axitinib, inhibits the growth of new blood vessels in the brain, a characteristic shared by both cancerous tumors and Alzheimer’s disease, but this characteristic represents a new target for Alzheimer’s disease therapies.

Mice with Alzheimer’s disease who underwent the therapy not only showed reduced blood vessels and other markers of Alzheimer’s disease in their brains, but also performed remarkably well in tests designed to measure learning and memory.

“We’re really, really excited because these results suggest that we can reuse approved cancer drugs for use as treatments for Alzheimer’s disease,” said Professor Wilf Jefferies, lead author of the study and lead researcher at the Center. for Blood Research, Vancouver Prostate Center. and Michael Smith Laboratories. “It could shorten clinical development by several years.”

Alzheimer’s disease is estimated to affect 50 million people worldwide. The condition is characterized by cognitive decline, memory loss, and dysfunctional changes in the brain.

Potential treatments for Alzheimer’s disease have shown promise in animal models before, but have failed in clinical trials. Typically, these strategies target a protein called tau or a fragment of a protein called beta-amyloid, but UBC researchers chose a different approach. They left the traditional targets aside and instead focused on fighting angiogenesis: the growth of new blood vessels.

“The vast majority of clinical trials have directly or indirectly targeted beta-amyloid or tau protein,” said Professor Jefferies. “Other than a few controversial recent results, there has been little success in these clinical trials. Thus, a lot of effort seems to have been directed towards the wrong targets to reverse Alzheimer’s disease.

Preparing the ground for the present study, the early pioneering work of Professor Jefferies had shown that the proliferation of blood vessels compromises the blood-brain barrier in patients with Alzheimer’s disease. This barrier, made up largely of blood vessels, is believed to protect the brain from infections because foreign molecules cannot easily pass through it.

Since cancerous tumors also depend on the growth of new blood vessels to survive and thrive, the researchers felt that a proven cancer drug could stop the Alzheimer’s disease process.

“Axitinib, the anticancer drug we used, blocks a receptor in the brain called the tyrosine kinase receptor, which is partly responsible for the formation of blood vessels,” explained Dr. Chaahat Singh, the first author of the article and postdoctoral researcher working with Professor Jefferies. “It prevents the growth of abnormal blood vessels, which then prevents many downstream effects.”

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

In a typical test, a mouse is trained to achieve a reward through a maze. A healthy mouse can find its way back to the reward, while an animal with symptoms of Alzheimer’s disease cannot.

So far, the treatment has only been applied to mice. Clinical trials will be needed to evaluate the effectiveness of this treatment in patients with Alzheimer’s disease, as well as the consideration of the long-term use of anticancer drugs in people living with Alzheimer’s disease. , who are mostly elderly.

Still, researchers are optimistic. If Axitinib works well in humans, reuse of an already approved drug could advance its use for Alzheimer’s disease more quickly.

“Researchers, including myself, have been disappointed to see that many clinical trials in Alzheimer’s disease fail to meet their clinical goals,” said Professor Jefferies. “The therapeutic approach we have discovered provides an opportunity to revise the clinical treatment of Alzheimer’s patients, which I think is absolutely necessary at this point for the field to move forward. “

Reference: Singh CSB, Choi KB, Munro L, Wang HY, Pfeifer CG, Jefferies WA. Reversing the pathology in a preclinical model of Alzheimer’s disease by hacking cerebrovascular neoangiogenesis with advanced anticancer treatments. EBioMedicine. 2021; 71. doi: 10.1016 / j.ebiom.2021.103503

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