Anti-cancer drug could help treat early-stage Alzheimer’s disease

An international team of scientists has discovered that A type of drug developed to treat cancer could be useful in treating neurodegenerative diseases such as Alzheimer’s. a pathology that affects the metabolism of the brain and causes loss of thinking, memory and language.

A team led by Stanford University focused on a key regulator of brain metabolism known as kynurenine pathwaywhich regulates the production of lactate, which nourishes the brain’s neurons and keeps synapses healthy.

In the brains of Alzheimer’s patients, kynurenine is overactive. In a study of mice with Alzheimer’s disease, researchers looked for the opposite effect by blocking lThe enzyme IDO1, which produces kynurenine, which made it possible to restore the animals’ brain metabolism and improve, even restore, cognitive functions.

Given these results, they suggest that IDO1 inhibitors, which are currently being developed to treat many types of cancer such as melanoma, leukemia and breast cancer, could also be used to treat it. treat early stages of neurodegenerative diseaseschronic diseases for which there is no preventive treatment.

Details of the study, which was conducted in collaboration with the Salk Institute for Biological Studies and Pennsylvania State University, were published Thursday in the journal Science. Only in Spain, Alzheimer’s disease affects more than 700,000 people over the age of 40.and this figure is expected to reach two million by 2050 (13 million in the case of the United States).

Lactate deficiency

Alzheimer’s disease affects the parts of the brain that control thinking, memory, and language through a progressive and irreversible loss of synapses and neural circuits. As the disease progresses, symptoms can worsen, from mild memory loss to loss of the ability to communicate and respond to the environment.

Modern treatments for this disease are aimed at controlling symptoms and slowing progression.acting on the accumulation of amyloid and tau plaques in the brain, but there are no approved methods for combating the onset of the disease.

“The scientists focused on the side effects of what we identified as a problem in brain function,” explains Pravina Prasad, a researcher at the University of Pennsylvania and co-author of the paper.

“The treatments available today target peptides that are likely the result of a more serious problem that we can treat before those peptides start to form plaques, because if we target brain metabolism, we can not only slow the progression of the disease, but we can also invest in it,” he notes.

To do this, the researchers examined kynurenine, which regulates the production of lactate in the brain, which feeds brain neurons and helps maintain healthy synapses, and the enzyme IDO1.

“Inhibiting this enzyme, especially with compounds that have already been studied in human clinical trials against cancer, could be a big step forward in finding ways to protect our brains from damage caused by aging and neurodegeneration,” explains Katrin Andreasson, a Stanford professor and lead author of the study.

And since IDO1 is well known in oncology and drugs to suppress its activity and kynurenine production are already undergoing clinical trials, the team was able to bypass the lengthy work of identifying new drugs and almost immediately begin testing on laboratory mice.

During the course of these studies, they found that the drugs improved glucose metabolism in the hippocampus, corrected poor astrocyte function, and improved the spatial memory of mice.

Research on patients

Andreasson believes that the connection between neuroscience, oncology and pharmacology could help speed up the commercialization of drugs if their effectiveness is demonstrated in ongoing human clinical trials against cancer. “We hope that IDO1 inhibitors developed for cancer can be repurposed for the treatment of Alzheimer’s disease,” he emphasizes.

The next step will be to test IDO1 inhibitors in people with Alzheimer’s disease to see if they show similar improvements in cognition and memory.