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 diseasea 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 patients with Alzheimer’s disease kynurenine is overactivated. In search of the opposite effect, in a study on mice with Alzheimer’s disease, the researchers blocked the enzyme IDO1 producing kynurenine, which allowed the restoration of the animals’ brain metabolism and improve and even restore cognitive functions.

Given these results, they suggest that IDO1 inhibitors are currently being developed to treat many types of cancer, such as melanoma, leukemia and breast cancerthey could It can also be used to treat early stages of neurodegenerative diseases.chronic 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 in the journal Science.

Only in Spain is there Alzheimer’s disease 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 languageas a result of progressive and irreversible loss of synapses and neural circuits.

As the disease progresses symptoms may worsenfrom mild memory loss to loss of the ability to communicate and respond to the environment.

Modern methods of treating this disease are aimed at control symptoms and slow progressionacting on the accumulation of amyloid and tau plaques in the brain, but there are no approved methods for combating the onset of the disease.

“Scientists have focused on the side effects of what we have identified as the problem is how the brain feeds itself“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.

For this, Researchers have been studying kynureninewhich regulates the production of lactate in the brain, which nourishes brain neurons and helps maintain healthy synapses, and the enzyme IDO1.

“Inhibition of this enzyme, especially with compounds that have already been investigated in human clinical trials against cancer, may represent a a big step forward in finding ways to protect our brains damage caused by aging and neurodegeneration,” explains Kathrin 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 in clinical trials, the team was able to avoid the lengthy work of identifying new drugs and start testing on mice laboratory almost immediately.

In them they confirmed that Drugs improve glucose metabolism in the hippocampuscorrected poor astrocyte function and improved spatial memory in mice.

Research on patients

Andreasson believes that the links between neuroscience, oncology and pharmacology can help accelerate the commercialization of drugs if its effectiveness is demonstrated in ongoing human clinical trials against cancer.

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

Next step testing IDO1 inhibitors in humans with Alzheimer’s disease to see if they show similar improvements in cognition and memory.