The gas xenon, like the other noble, or inert, gases, is known for doing very little. The class of elements, because of its molecular structure, don’t typically interact with many chemicals.
But a new mouse study shows one possible use case for xenon — as a treatment for Alzheimer’s disease. The paper, published Wednesday in Science Translational Medicine, shows the potential of inhaled xenon to activate the brain’s immune cells, called microglia, to break down plaques that are a hallmark of Alzheimer’s as well as reduce inflammation in the brain. While the study was conducted in mice, it has already inspired a Phase 1 clinical trial, which is currently recruiting patients and set to start this year.
Most approaches to treating Alzheimer’s have focused on targeting beta-amyloid plaques that build up in the brain. Three drugs have been approved in recent years, but those treatments have not panned out to be as effective as researchers hoped, including one, Aduhelm, that was withdrawn from the market. Some researchers have turned to other targets, like microglia, as potential alternatives.
The new study “offers a ray of hope in this direction, providing a scaffold on which microglial-focusing clinical studies can hinge to offer a new approach to treatment,” said Ifeoluwa Awogbindin, a neuroimmunologist at the University of Victoria in Canada, who was not part of the new study.
Physicians have long used xenon in other ways: as an anesthetic and to treat brain damage that results from a lack of oxygen. Some studies had previously shown that xenon could protect neurons exposed to a toxic solution in mouse cell cultures. Patrick Pierre Michel, a cell biologist at the Paris Brain Institute who conducted those studies, said the new results are promising and, given the earlier findings, unsurprising.
The new study takes cell culture research a step further. The team, from Washington University in St. Louis and Brigham and Women’s Hospital in Boston, used a set of different mouse models representing different characteristics of Alzheimer’s disease to show that xenon changes the behavior of microglia, an immune cell that can be found in the spinal cord and the brain. During the course of Alzheimer’s, microglia have been shown to lose their ability to break down beta-amyloid proteins that accumulate between neurons and harm the brain. But the new study shows xenon helped microglia regain that ability and also reduced inflammation that often accompanies Alzheimer’s.
In two mouse models that express proteins that are hallmarks of Alzheimer’s, tau and beta-amyloid, mice exposed to xenon had lower levels of the two proteins. In mice with APOE4 — a genetic variant that elevates a person’s risk of Alzheimer’s — animals treated with xenon did better at tests of cognition and had less deterioration in the brain.
“It’s a really out-of-the box approach,” said Oleg Butovsky, a neuroimmunologist at Harvard University, and one of the authors of the new study. Based on the results, he said the researchers have gotten approval from the Food and Drug Administration and their institutional review boards to begin a Phase 1 trial to test the safety of the gas in healthy volunteers.
If the treatment worked in humans, it could serve as a relatively simple way to treat the disease — as it would just require an inhalation device.
“Everything in the paper is beautiful, but the final verdict will be after a Phase 2 clinical trial. If it reaches its end point with a positive effect on biomarkers and cognition, this is going to be very big,” Butovsky said.