Cancer Drug Holds New Potential in Treating Alzheimer’s Disease: Animal Study

IDO1 inhibitors show promise in reversing Alzheimer’s by restoring glucose metabolism and protecting neurons.

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Researchers from Stanford University found that drugs originally developed for cancer treatment, known as IDO1 inhibitors, could restore memory function and improve brain metabolism in preclinical trials, according to a new study published in the journal Science.

This class of drugs “wake up immune cells in cancer” and restore glucose metabolism in the brain by targeting a process known as the kynurenine pathway, Katrin Andreasson, the study’s senior author and a professor of neurology and neurological sciences at Stanford University School of Medicine, told The Epoch Times.

“This helps neurons function better, leading to healthier cells that can better resist the progression of Alzheimer’s diseases,” she added.

Potential Alzheimer’s Treatment

Current treatments for Alzheimer’s focus on managing symptoms or slowing progression, but indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors were shown to rescue Alzheimer’s-like symptoms in mice.

Alzheimer’s disease is characterized by a decline in cognitive function, often accompanied by reduced glucose metabolism in the brain. This decreased energy supply can impair neuronal function and contribute to the buildup of harmful proteins that form plaques and tangles.

The buildup of harmful proteins in the brain increases IDO1, a type of protein, which then produces a metabolite that disrupt glucose metabolism in the brain.

The cancer drug works by inhibiting the enzyme IDO1.

This improved the survival of neurons, which are brain cells that store and transmit messages, subsequently rescuing spatial memory and learning, in mice. It also restored glucose metabolism in the hippocampus, the brain area often first affected in Alzheimer’s.

This restoration enables neurons to become healthier and function better, helping them resist the progression of various pathologies.

Improving the energy metabolism of neurons may help delay the onset of Alzheimer’s in mouse models, Melanie McReynolds, a biochemist specializing in metabolic decline and aging, and co-author of the paper, said in an interview with The Epoch Times.

A New Approach to Fighting Alzheimer’s

Current Alzheimer’s treatments focus on symptoms management and slowing disease progression by targeting the build-up of harmful proteins in the brain.

The more recently approved drugs are antibodies that try to clear amyloid, the harmful proteins that build up in the brain, Andreasson said. Yet these drugs have had “a minimal effect on cognition.” IDO1 inhibitors target an entirely different mechanism which may offer patients an alternative treatment, she said.

The study found that while the drug didn’t lower the overall amount of harmful substances in the brain, it did help reduce the buildup of  amyloid proteins in the hippocampus, a key region affected in Alzheimer’s disease.

“We were pretty surprised ... at the magnitude of the reduction,” Andreasson said.

Healthier neurons generate less harmful proteins that clump together and cause them to die, which is central to the pathology of Alzheimer’s.

“People can have amyloid and actually be cognitively normal, but once the tau starts to spread, then that’s, that’s a very serious inflection point,” Andreasson said. If IDO1 inhibition can prevent this process and delay the onset of Alzheimer’s by even five years, it could significantly reduce the number of people who develop the disease, she added.

Challenges and Promises

Recent studies have raised concerns about the suitability of animal models for evaluating potential Alzheimer’s treatments.

A study published in Stem Cell Reports suggests that animal models may not be well-suited for evaluating potential Alzheimer’s treatments. An animal study published in the journals Animals did not show beneficial effects in clinical trials despite showing promising results during pre-clinical trials with animals.

Andreasson acknowledges the limitations of mouse models, noting that while they don’t capture the full complexity of Alzheimer’s in humans, they do enable investigation of harmful brain changes and potential treatments.

The researchers said they believed that the drug would be beneficial at any stage of the disease process. “I would hope that this mechanism would be relevant at early, middle, and late stages,” Andreasson said. “After all—your neurons—they do need energy no matter what state they’re in. So it seems intuitively that this could be something that could straddle from before to mid to late,” she added.

McReynolds added that blocking IDO1 enzymes showed protective benefits to both the tau and amyloid models, suggesting potential applications for various neurological disorders, including Parkinson’s to dementia.

For future studies, Andreasson outlined two main directions: closely examining astrocyte function in healthy people compared to those with neurodegenerative diseases, and investigating whether IDO1 inhibitors could treat Alzheimer’s in humans.

Meanwhile, McReynolds said that her lab focuses on understanding how metabolic balance is maintained or disrupted in aging and disease. Her main goal, she said, is to promote healthier aging by exploring the links between stress, metabolism, and disease, noting that stress-driven metabolic disruptions contribute to unhealthy aging and may be connected to conditions like Alzheimer’s.