A breakthrough study highlights Xenon gas as a potential game-changer in treating Alzheimer’s disease, demonstrating its ability to mitigate brain damage and improve cognitive functions in mouse models. A forthcoming clinical trial aims to test its efficacy in humans.
Most current treatments for Alzheimer’s disease focus on addressing amyloid plaques and tau tangles in the brain. However, researchers from Mass General Brigham and Washington University School of Medicine in St. Louis have identified a groundbreaking alternative: Xenon gas.
Their study demonstrated that inhaling Xenon gas reduced neuroinflammation, minimized brain atrophy, and promoted protective neuronal states in mouse models of Alzheimer’s disease. These findings, published today (January 15) in Science Translational Medicine, have paved the way for a phase 1 clinical trial in healthy volunteers, set to begin in early 2025.
Groundbreaking Research and Clinical Trials
“It is a very novel discovery showing that simply inhaling an inert gas can have such a profound neuroprotective effect,” said senior and co-corresponding author Oleg Butovsky, PhD, of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. “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.”
“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 and co-corresponding author David M. Holtzman, MD, from Washington University School of Medicine in St. Louis.
The Science Behind Xenon’s Effects
The exact causes of Alzheimer’s disease remain unclear, and there is currently no cure. More effective treatments are urgently needed. Alzheimer’s is marked by the buildup of proteins in the brain, such as tau and amyloid, which disrupt nerve cell communication. Over time, this leads to progressive brain damage, neuronal loss, and ultimately, death.
Microglia, the brain’s primary immune cells, act as the brain’s first line of defense, responding to any disruptions and playing a crucial role in maintaining brain function throughout life. However, when microglia become dysregulated, they contribute significantly to the progression of Alzheimer’s disease. Research from Dr. Butovsky’s lab has developed a method to study microglial responses to neurodegeneration, revealing that certain microglial phenotypes can be modulated to provide protective effects against Alzheimer’s.
Promising Preclinical Outcomes with Xenon
In this study, mouse models of Alzheimer’s disease were treated with Xenon gas that has been used in human medicine as an anesthetic and as a neuroprotectant for treating brain injuries. Xenon gas penetrates the blood-brain barrier, passing from the bloodstream directly into the fluid surrounding the brain. The team found that Xenon gas inhalation reduced brain atrophy and neuroinflammation and improved nest-building behaviors in the Alzheimer’s disease mouse models. It also induced and increased a protective microglial response that is associated with clearing amyloid and improving cognition. Together, these findings identify the promising potential of Xenon inhalation as a therapeutic approach that could modify microglial activity and reduce neurodegeneration in Alzheimer’s disease.
Future Directions and Clinical Potential
The clinical trial at Brigham and Women’s Hospital, which will initially only enroll healthy volunteers, is set to begin in the next few months.
As early phases of the clinical trial get underway to establish safety and dosage, the research team plans to continue to study the mechanisms by which Xenon gas achieves its effects in addition to its potential for treating other diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and eye diseases that involve the loss of neurons. The team is also devising technologies to help use Xenon gas more efficiently as well as potentially recycle it.
“If the clinical trial goes well, the opportunities for the use of Xenon gas are great,” said co-author Howard Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at BWH and principal investigator of the upcoming clinical trial. “It could open the door to new treatments for helping patients with neurologic diseases.”
Reference: “Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy” by Wesley Brandao, Nimansha Jain, Zhuoran Yin, Kilian L. Kleemann, Madison Carpenter, Xin Bao, Javier R. Serrano, Eric Tycksen, Ana Durao, Jen-Li Barry, Caroline Baufeld, Dilansu Guneykaya, Xiaoming Zhang, Alexandra Litvinchuk, Hong Jiang, Neta Rosenzweig, Kristen M. Pitts, Michael Aronchik, Taha Yahya, Tian Cao, Marcelo Kenzo Takahashi, Rajesh Krishnan, Hayk Davtyan, Jason D. Ulrich, Mathew Blurton-Jones, Ilya Ilin, Howard L. Weiner, David M. Holtzman and Oleg Butovsky, 15 January 2025, Science Translational Medicine.
DOI: 10.1126/scitranslmed.adk3690
Authorship: In addition to Butovsky and Weiner, Mass General Brigham authors include 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, Additional authors include 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 on patent no. 17/914,061 (held by Brigham and Women’s Hospital and General Biophysics) for using Xe to treat neurodegenerative diseases. Butovsky is co-founder and is on the scientific advisory board of Glial Therapeutics and GliaX; collaborates with GSK and Regulus Therapeutics; has research funding from Sanofi, GSK; and consults for/has received honoraria from UCB, Camp4, Ono Pharma USA, General Biophysics. Holtzman co-founded and is on the scientific advisory board of C2N Diagnostics. Holtzman is on the scientific advisory board of Denali, Genentech, and Cajal Neurosciences and consults for Asteroid Therapeutics. Blurton-Jones co-founded and is on the scientific advisory board of NovoGlia Inc. Ilin is the founder and CEO of General Biophysics LLC.
Funding: This study was funded by National Institutes of Health (NIH) (STTR R41AG073059, R01 AG051812 R01 AG054672, R01 NS088137 R01 AG075509, RF1 NS090934, P30 AG066519, U19 AG06970101); Cure Alzheimer Fund; Massachusetts Center for Alzheimer Therapeutic Science (MassCATS); BrightFocus Foundation 2020A016806; Alzheimer’s Association research fellowship AARF-21-846786; National Multiple
Sclerosis Society FG-2108-38372; Department of Defense W81XWH-22-1-0945
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16 Comments
This sounds a bit like huffing as it was called back in the 90’s. I think it too reduced inflammation in the brain albeit recreationally.
Where do I volunteer?
Pls contact us for trial.
How do we sign up?
Joseph & Victoria
This is great news. I’m 64 and worry about about dementia.
Sorry about the ozone hole though 🫣
Whoops, feon caused the ozone hole. I don’t know about zenon.
Perhaps I need that treatment sooner than I thought.
Freon
Xenon
How do we sign up to participate in the study. My wife was diagnosed with early onset Alzheimer’s in 2020. You mentioned the study would involve not healthy people, would my wife’s diagnosis disqualify her from the study?
If xenon is truly inert, how does it work? Do other ‘inert’ gases also work the same way”
As far as I know, the reasons xenon would work on the brain isn’t known to science, but it blocks glutamate receptors in the brain, an NMDA and AMPA antagonist like other anesthetics. It reportedly causes a powerfully joyful narcosis. It may be addictive, or the intoxication and joy can lead to carelessly increasing the dose. The cost to purify a dose of xenon from the air is very high, and it isn’t generally available as a therapy. There was a Xenon Clinic in Prague (Czechia), but unfortunately its two proprietors kept dying of asphyxia, however joyfully.
I have no personal experience with it, but to me it sounds very similar to nitrous oxide laughing gas, and they probably works the same way at a much lower cost. I did a quick search, and found “Neuroprotection by nitrous oxide: facts and evidence” (Crit Care Med, 2008 September), so sounds like it might be an available replacement. If you’re interested in someone’s personal experience, Season 3 Episode 3 of Hamilton’s Pharmacopoeia covered it, “Xenon – The Perfect Anesthetic”. I think it might be on youtube. It was a great series from the heyday of VICE, scientific and entertaining and a little goofy, presented by Errol Morris’ son.
Where do I sign up ?
I can’t say how it would work, but I can tell you that xenon is a noble gas – element #54, on the right hand side of the periodic table, the electron shells are full. Therefore it can’t bond with any other atoms.
It has “attachment issues”.
Please post links to studies (when available) elucidating the mechanisms of action, thanks.
Can Xenon bars be far behind?
Can it help with possible wernickes Korsokoff syndrome.Dementia?!
If xenon can treat Alzheimer’s,an hopefully multiple sclerosis etc,where can I sign my dad up.i do have a question if these gases xenon can penetrate the brain blood barrier to heal then what in our air an environment has caused these diseases,there’s a link ….thku