Most current treatments aimed at preventing Alzheimer’s disease concentrate on amyloid plaques and tau tangles that build up in the brain. However, recent research has introduced a groundbreaking method: the use of Xenon gas. According to the study, inhaling Xenon gas helped to reduce neuroinflammation, lessen brain shrinkage, and enhance protective states of neurons in mouse models of Alzheimer’s disease. A phase 1 clinical trial for this treatment in healthy individuals is set to commence in early 2025.
Today, many treatments for Alzheimer’s disease target the amyloid plaques and tau tangles that form in the brain, but exciting new research from Mass General Brigham and Washington University School of Medicine in St. Louis highlights a new and noteworthy approach: inhaling Xenon gas. This study found that using Xenon gas decreased neuroinflammation, minimized brain atrophy, and promoted protective neuron conditions in mouse models of Alzheimer’s disease. The findings are available in Science Translational Medicine, and a phase 1 clinical trial involving healthy participants will start in early 2025.
“This is a remarkable discovery showing that simply inhaling an inert gas can have major neuroprotective benefits,” stated Oleg Butovsky, PhD, the senior and co-corresponding author from the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH), part of the Mass General Brigham healthcare system. “A significant challenge in Alzheimer’s research is creating medications that effectively cross the blood-brain barrier – but Xenon gas can do this. We are eager to see the results of this innovative method in human trials.”
“It’s exciting that in both animal models demonstrating different aspects of Alzheimer’s – one showing amyloid buildup and the other tau buildup – Xenon exhibited protective effects in both cases,” remarked David M. Holtzman, MD, another senior and co-corresponding author from Washington University School of Medicine in St. Louis.
The exact causes of Alzheimer’s disease remain unclear; there is no known cure, and better treatment options are urgently needed. The disease is marked by the accumulation of proteins in the brain, such as tau and amyloid, which disrupt communication between nerve cells and contribute to progressive neurological decline and ultimately cell death. Microglia, the primary immune cells in the brain, act as ‘first responders’ to disturbances, playing a vital role in brain function throughout development. Dysregulation of microglia is a significant factor in Alzheimer’s. Previously, Butovsky’s laboratory developed a method to examine how microglia react to neurodegeneration and established that a specific type of microglia can be adjusted in a way that protects against Alzheimer’s damage.
In their research, mouse models of Alzheimer’s disease were exposed to Xenon gas, which has been utilized in human medicine as an anesthetic and neuroprotectant for traumatic brain injuries. The team discovered that inhaling Xenon gas minimized brain atrophy, lowered neuroinflammation, and enhanced nesting behavior in these mouse models. It also encouraged a protective microglial response linked to clearing amyloid and improving cognitive function. Overall, these findings underscore the potential of Xenon inhalation as a therapeutic strategy that may modify microglial activity and slow down neurodegeneration associated with Alzheimer’s disease.
The clinical trial at Brigham and Women’s Hospital will initially only recruit healthy volunteers and is scheduled to start in the coming months.
As early stages of the clinical trial begin to assess safety and dosage, the research group plans to delve deeper into how Xenon gas exerts its effects, as well as explore its potential to treat other conditions, including multiple sclerosis, amyotrophic lateral sclerosis, and various eye diseases involving neuronal loss. The team is also working on improving techniques for the effective use of Xenon gas and exploring recycling options.
“If the clinical trial yields positive results, the potential applications for Xenon gas are vast,” shared co-author Howard Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at BWH and the principal investigator for the upcoming trial. “This could pave the way for new treatments that assist patients suffering from neurological disorders.”
Authorship includes Butovsky and Weiner, along with Mass General Brigham contributors Wesley Brandao, Zhuoran Yin, Kilian L. Kleemann, Madison Carpenter, Ana Durao, Jen-Li Barry, Caroline Baufeld, Dilansu Guneykaya, Xiaoming Zhang, Neta Rosenzweig, Kristen M. Pitts, Michael Aronchik, Taha Yahya, Tian Cao, Marcelo Kenzo Takahashi, Rajesh Krishnan, as well as others including Nimansha Jain, Xin Bao, Javier R. Serrano, Eric Tycksen, Alexandra Litvinchuk, Hong Jiang, Hayk Davtyan, Jason D. Ulrich, Mathew Blurton-Jones, Ilya Ilin, and David M. Holtzman.
Disclosures: Butovsky, Ilin, Weiner, Yin, and Brandao are co-inventors of patent no. 17/914,061 (held by Brigham and Women’s Hospital and General Biophysics) for using Xenon (Xe) in treating neurodegenerative diseases. Butovsky is a co-founder and scientific advisory board member of Glial Therapeutics and GliaX; collaborates with GSK and Regulus Therapeutics; receives research funding from Sanofi and GSK; and consults for/has received compensation from UCB, Camp4, Ono Pharma USA, and General Biophysics. Holtzman co-founded C2N Diagnostics and is part of the advisory board for Denali, Genentech, and Cajal Neurosciences, besides consulting for Asteroid Therapeutics. Blurton-Jones co-founded NovoGlia Inc. and Ilin is the founder and CEO of General Biophysics LLC.
Funding: This study received financial support from the National Institutes of Health (NIH) through multiple grants including STTR R41AG073059, R01 AG051812, R01 AG054672, R01 NS088137, R01 AG075509, RF1 NS090934, P30 AG066519, and U19 AG06970101; the Cure Alzheimer Fund; the Massachusetts Center for Alzheimer Therapeutic Science (MassCATS); the BrightFocus Foundation (grant 2020A016806); an Alzheimer’s Association research fellowship (AARF-21-846786); the National Multiple Sclerosis Society (FG-2108-38372); and the Department of Defense (W81XWH-22-1-0945).
