Chemotherapy drug reverses Alzheimer’s symptoms in mice
Axitinib, a common chemotherapy drug, restored memory and cognitive function in mouse models, representing a potential Alzheimer’s treatment.
Researchers from the University of British Columbia (UBC), Canada, have discovered that the anticancer drug, Axitinib, can restore memory and cognitive function in the brains of mice. The team hope that the drug could be repurposed to treat Alzheimer’s disease in the future.
Potential Alzheimer’s treatments have shown promise in animal models before, but failed in clinical trials. Typically, these strategies target tau or beta-amyloid, but the researchers chose a different approach. They left the traditional targets alone and instead focused on curbing angiogenesis.
“The vast majority of clinical trials have either directly or indirectly targeted beta-amyloid or tau,” explained senior author Professor Wilf Jefferies. “A great deal of effort appears to have been directed toward the wrong targets for reversing Alzheimer’s disease.”
Jefferie’s prior work had shown that the proliferation of blood vessels compromises the blood-brain barrier in patients with Alzheimer’s disease. This barrier is believed to protect the brain from infection because foreign molecules cannot easily cross it. Since cancerous tumours 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.
In the study, published in EBioMedicine, Axitinib was shown to inhibit the growth of new blood vessels in the brain, a feature shared by both cancer tumours and Alzheimer’s disease, but this hallmark represents a new target for Alzheimer’s therapies.
“Axitinib, the anticancer drug we used, blocks a receptor in the brain called a tyrosine kinase receptor, which is partly responsible for spurring blood vessel formation,” explained Dr Chaahat Singh, the paper’s first author. “It stops abnormal blood vessels from growing, which then prevents many downstream effects.” By using Axitinib for one month, the researchers dramatically reduced blood vessel growth, restored the blood-brain barrier and most significantly, helped mice perform better on cognitive tests.
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The treatment has only been applied to mice so clinical trials will be needed to assess the effectiveness of this treatment in patients 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 elders.
However, the team are still hopeful the drug could be used in humans. “Researchers including myself have been disappointed in observing numerous clinical trials for Alzheimer’s disease fail to reach their clinical endpoints,” said 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.”
Alzheimer's disease (AD)
University of British Columbia (UBC)