Could Drugs Used to Fight Cancer Also Slow Alzheimer's?

August 23, 2024
Dennis Thompson HealthDay Reporter

A new type of cancer drug might help treat brain diseases like Alzheimer’s, mouse studies suggest.

The drugs block an enzyme called indoleamine-2,3-dioxygenase 1 (IDO1), researchers reported.

IDO1 inhibitors are being developed as a treatment for cancers like melanoma, leukemia and breast cancer, researchers said. The drugs fight cancer by blocking cancer cells’ ability to evade the immune system.

But the drugs also might be able to treat the early stages of degenerative brain diseases like Alzheimer’s, because the same enzyme has been implicated in problems with the way brain cells are fueled, researchers said.

“Inhibiting this enzyme, particularly with compounds that have been previously investigated in human clinical trials for cancer, could be a big step forward in finding ways to protect our brains from the damage caused by aging and neurodegeneration,” said senior researcher Dr. Katrin Andreasson, a professor of neurology and neurological sciences at the Stanford University School of Medicine.

The IDO1 enzyme breaks down tryptophan, the same molecule in turkey that can make you sleepy, into a compound called kynurenine, researchers explained.

The body’s production of kynurenine plays a critical role in how the brain is fueled using blood sugars, also called glucose, researchers said.

When IDO1 generates too much kynurenine, it interferes with the energy needed to power the brain’s synapses, researchers found in lab mice.

But suppressing IDO1 increased energy flow to the synapses in mice and restored proper brain function, researchers discovered.

“The brain is very dependent on glucose to fuel many processes, so losing the ability to effectively use glucose for metabolism and energy production can trigger metabolic decline and, in particular, cognitive decline,” said researcher Dr. Paras Minhas, a resident at Memorial Sloan Kettering Cancer Center in New York City.

One theory of Alzheimer’s disease holds that the buildup of toxic proteins like amyloid beta and tau disrupts the blood sugar metabolism needed to fuel the healthy brain, researchers said.

Studying mouse models of Alzheimer’s in which amyloid plaques or tau tangles cause brain degeneration, researchers found that blocking IDO1 actually protected brain function against both types of toxic brain proteins.

Researchers think kynurenine becomes over-activated by the buildup of amyloid plagues and tau tangles in the brain.

“We were surprised that these metabolic improvements were so effective at not just preserving healthy synapses, but in actually rescuing behavior,” Andreasson said in a Stanford news release. “The mice performed better in cognitive and memory tests when we gave them drugs that block the kynurenine pathway.”

It’s particularly important that the IDO1 inhibitors worked against the bad effects of both amyloid and tau, Andreasson added.

“We also can’t overlook the fact that we saw this improvement in brain plasticity in mice with both amyloid and tau mice models. These are completely different pathologies, and the drugs appear to work for both,” Andreasson said. “That was really exciting to us.”

The findings were published Aug. 22 in the journal Science.

The next step will be to test IDO1 inhibitors in people with Alzheimer’s disease, researchers said. They are working on clinical trials that could occur in the near future.

“We’re hopeful that IDO1 inhibitors developed for cancer could be repurposed for treatment of Alzheimer’s disease,” Andreasson said.

More information

The Alzheimer’s Association has more about Alzheimer’s disease.

SOURCE: Stanford University, Penn State, news releases, Aug. 22, 2022

Cancer: Misc.Dementia