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August 22, 2024 – 8:00 PM
Science Editorial, Aug 22 (EFE).- 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 Alzheimer’s, a pathology that affects the brain’s metabolism and causes loss of thought, memory and language.
The team, led by Stanford University, 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 enzyme IDO1 that generates kynurenine, which allowed the brain metabolism of the animals to be restored and cognitive function to be improved, even restored.
These results suggest that IDO1 inhibitors currently being developed as treatments for many types of cancer, such as melanoma, leukemia and breast cancer, could also be used to treat the early stages of neurodegenerative diseases, chronic conditions for which there are no 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 the age of 40, and the figure is expected to reach two million by 2050 (13 million in the United States).
Lack of lactate
Alzheimer’s disease affects the parts of the brain that control thought, memory and language, as a result of the progressive and irreversible loss of synapses and neural circuits.
As the disease progresses, symptoms may increase, from mild memory loss to the loss of the 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 identified as a problem in the way the brain feeds itself,” said 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 human cancer clinical trials, could be a major step forward in finding ways to protect our brains from damage caused by aging and neurodegeneration,” said Katrin Andreasson, a professor at Stanford and senior 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.
They found that the drugs improved glucose metabolism in the hippocampus, corrected poor astrocytic performance, and improved spatial memory in mice.
Patient trials
Andreasson believes the connection between neuroscience, oncology and pharmacology could help speed up the commercialisation of drugs if their 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 Alzheimer’s patients to see if they show similar improvements in cognition and memory. EFE
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