An international team of scientists has discovered that A type of drug developed to treat cancer could be useful for treating neurodegenerative diseases such as Alzheimera pathology that affects the brain’s metabolism and causes loss of thought, memory and language.
The team, led by the Stanford Universityhas focused on a critical regulator of brain metabolism known as the kynurenine pathway, which regulates the production of lactate, which nourishes brain neurons and keeps synapses healthy.
In the brains of Alzheimer’s patients, kynurenine is overactivated. Seeking the opposite effect, in a trial with mice with Alzheimer’s, researchers blocked the IDO1 enzyme which generates kynurenine, which allowed the animals’ brain metabolism to be restored and cognitive function to be improved and even restored.
In view of these results, they suggest that IDO1 inhibitors currently being developed as a treatment for many types of cancer, such as melanoma, leukemia and breast cancer, They could also be used to treat the early stages of neurodegenerative diseases.chronic ailments that lack preventive treatments.
Details of the study, which was conducted in collaboration with the Salk Institute for Biological Studies and Pennsylvania State University, among others, were published Thursday in the journal Science.
In Spain alone, Alzheimer’s affects more than 700,000 people over 40 years of age.and by 2050 the figure is expected to reach two million, and 13 million in the case of the United States.
Lack of lactate
Alzheimer’s disease affects the parts of the brain that control thinking, memory and languageas a result of the progressive and irreversible loss of synapses and neuronal circuits.
As the disease progresses, Symptoms may progress from mild memory loss to loss of ability to communicate and respond to the environment..
Current treatments for the disease focus on controlling symptoms and slowing progression by targeting the buildup of amyloid and tau plaques in the brain, but there are no approved treatments to combat the onset of the disease.
“Scientists have focused on the side effects of what we identify as a problem in the way the brain feeds itself“explains Praveena Prasad, a researcher at Penn State and co-author of the paper.
“Currently available therapies remove peptides that are likely the result of a larger problem that we can treat before those peptides start forming plaques because if we act on the brain’s metabolism, we can not only slow the progression of the disease, but reverse it,” he says.
To do this, the researchers investigated kynurenine, which regulates the production of lactate in the brain – which nourishes brain neurons and helps keep synapses healthy – and the enzyme IDO1.
“Inhibiting this enzyme, especially with compounds that have already been investigated in clinical trials against cancer in humans, could be a major step forward in the search for ways to protect our brains from damage caused by aging and neurodegeneration.”explains Katrin Andreasson, a professor at Stanford and lead author of the study.
And because IDO1 is well known in oncology and there are already drugs in clinical trials to suppress its activity and kynurenine production, the team was able to bypass the lengthy work of identifying new drugs and begin testing in laboratory mice almost immediately.
In them they found that The drugs improved glucose metabolism in the hippocampuscorrected poor astrocytic performance and improved spatial memory in mice.
Patient trials
Andreasson believes that the connection between neuroscience, oncology and pharmacology could help accelerate the commercialization of drugs if its efficacy is demonstrated in ongoing human clinical trials against cancer.
“We are hopeful that IDO1 inhibitors developed for cancer can be repurposed for the treatment of Alzheimer’s,” he said.
The next step is to test IDO1 inhibitors in human patients with Alzheimer’s. to see if they show similar improvements in cognition and memory.