Inhaling the inert gas xenon could protect against neurodegeneration and offset some of the key features of Alzheimer’s disease, preclinical studies suggest.
The findings in mice reveal a novel therapeutic application for this noble gas, which has been used as an anesthetic in humans since the mid-20th century and as a neuroprotectant for treating brain injuries.
The results have led to a phase I clinical trial in healthy human volunteers, set to begin this year.
Breathing in the chemical element modified the activity of microglia immune cells that play a key role in brain development among the mouse models of Alzheimer’s disease, leading to a protective response.
Xenon also reduced inflammation and brain atrophy and improved nest-building behavior in the animals, according to the findings published in Science Translational Medicine.
“It is a very novel discovery showing that simply inhaling an inert gas can have such a profound neuroprotective effect,” said senior researcher Oleg Butovsky, PhD, from Brigham and Women’s Hospital and Harvard Medical School.
“One of the main limitations in the field of Alzheimer’s disease research and treatment is that it is extremely difficult to design medications that can pass the blood-brain barrier—but Xenon gas does. We look forward to seeing this novel approach tested in humans.”
Although defective microglia contribute to the onset of Alzheimer’s disease, there are currently no clinically available therapies that can yet modulate these cells.
In the quest for such a treatment, Butovsky and colleagues examined the impact of the heavy gas xenon in several mouse models of early- and late-stage Alzheimer’s disease.
They found that microglia were triggered into transitioning into a unique, intermediate activation state through boosted signaling of interferon (IFN)-γ, a key cytokine involved in immune response.
This activation state allowed the microglia to break down harmful proteins and diminished their proinflammatory action.
Xenon induced microglial phagocytosis and reduced the spread of amyloid plaques— enhancing amyloid plaque compaction in the brain—as well as decreasing the number of disease-linked, dystrophic neurites.
In one of the mouse models with abnormal tau protein deposits in the brain, xenon gas inhalation alleviated brain atrophy and neuroinflammation and resulted in better nest-building behaviors.
In another mouse model involving amyloidosis, in which there are abnormal deposits of amyloid protein, xenon acted upon CD8+ cells in a way that boosted IFN-γ signaling, with IFN-γ blockade impacting this effect.
The authors noted that the three classical hallmarks of Alzheimer’s disease are β-amyloid peptide deposition, tau tangles, and microglial activation.
“It is exciting that in both animal models that model different aspects of Alzheimer’s disease, amyloid pathology in one model and tau pathology in another model, that xenon had protective effects in both situations,” said senior author David M. Holtzman, MD, from the Washington University School of Medicine in St. Louis.
