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 may be useful for treating neurodegenerative diseases such as Alzheimer’s disease, 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 critical regulator for brain metabolism, known as kynurenine, which regulates the production of lactate, which nourishes the brain’s neurons and keeps synapses healthy.

In the brains of patients with Kynurenine is overactive in Alzheimer’s disease. In a study on mice with Alzheimer’s disease, looking for the opposite effect, the researchers blocked the enzyme IDO1, which produces kynurenine, which allowed them to restore the animals’ brain metabolism and improve, even restore, cognitive function.

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, They can also be used to treat early stages of neurodegenerative diseases – chronic conditions for which there is no preventive treatment.

Details of the study conducted in the city of collaboration with the Salk Institute for Biological Studies and Pennsylvania State University, among others, were published Thursday in the journal Science.

Only in Spain is there Alzheimer’s disease It affects more than 700,000 people over 40 years of age. 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, as a result of progressive and irreversible loss of synapses and neural circuits.

As the disease progresses, symptoms may worsen, ranging from slight memory loss before loss the ability to communicate and respond to the environment.

Modern methods of treating this disease are aimed at control symptoms and slow progression, It acts on the accumulation of amyloid and tau plaques in the brain, but there are no approved methods to combat the onset of the disease.

“Scientists have focused their attention on side effects “what we identified as a problem in brain function,” explains Praveena Prasad, a researcher at the University of Pennsylvania and co-author of the paper.

“Currently available treatments target peptides that are likely the result of a more serious problem “What we can do is treat before these peptides start to form plaques, because if we target brain metabolism, we can not only slow down the progression of the disease, but reverse it,” he points out.

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

“Inhibition of this enzyme, especially by compounds that have already been investigated in cancer clinical trials in humans, could be a big step forward in the search for 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 well known in oncology and there are already drugs at the clinical trial stage to suppress its activity and the production of kynurenine, the team managed to bypass the long work of identifying new drugs and almost immediately begin testing on laboratory mice.

They checked that the drugs improving glucose metabolism in the hippocampus, They corrected poor astrocyte function and improved spatial memory in mice.

Research on patients

Andreasson believes that the connection between neurobiology, oncology and pharmacology could help speed up the commercialization of drugs if they are proven effective in ongoing human clinical trials against cancer.

“We hope that IDO1 inhibitors developed for cancer treatment will be able to be reused in the treatment of Alzheimer’s disease.” 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.