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.
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
News
A Breath Away From a Cure: How Xenon Gas Could Transform Alzheimer’s Treatment
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 [...]
False Memories Under Fire: Surprising Science Behind What We Really Recall
New research challenges the ease of implanting false memories, highlighting flaws in the influential “Lost in the Mall” study. By reexamining the data from a previous study, researchers found that many supposed false memories [...]
Born Different? Cambridge Scientists Uncover Innate Sex Differences in Brains
Cambridge researchers found that sex differences in brain structure exist from birth, with males having more white matter and females more grey matter, highlighting early neurodiversity. Research from the Autism Research Centre at the University [...]
New study shows risk factors for dementia – virus causes deposits in the brain
Research into the causes of Alzheimer's is not yet complete. Now a new study shows that head trauma can activate herpes viruses and promote the disease. Frankfurt am Main – As a neurodegenerative disease, [...]
Are Machines Truly Thinking? Modern AI Systems Have Finally Achieved Turing’s Vision
Modern AI systems have fulfilled Turing’s vision of machines that learn and converse like humans, but challenges remain. A new paper highlights concerns about energy consumption and societal inequality while calling for more robust [...]
The Surprising Link Between Smell, Sound, and Emotions
New research reveals how smell and hearing interact in the brain to drive social behavior, using mouse maternal instincts as a model. Imagine you’re at a dinner party, but you can’t smell the food [...]
Brain cells age at different rates
As our body ages, not only joints, bones and muscles wear out, but also our nervous system. Nerve cells die, are no longer fully replaced, and the brain shrinks. "Aging is the most important risk factor [...]
Long COVID Breakthrough: Spike Proteins Persist in Brain for Years
Researchers have discovered that the SARS-CoV-2 spike protein persists in the brain and skull bone marrow for years after infection, potentially leading to chronic inflammation and neurodegenerative diseases. Researchers from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) have [...]
Water-Resistant Paper Could Revolutionize Packaging and Replace Plastic
A groundbreaking study showcases the creation of sustainable hydrophobic paper, enhanced by cellulose nanofibres and peptides, presenting a biodegradable alternative to petroleum-based materials, with potential uses in packaging and biomedical devices. Researchers aimed to [...]
NIH Scientists Discover Game-Changing Antibodies Against Malaria
Novel antibodies have the potential to pave the way for the next generation of malaria interventions. Researchers at the National Institutes of Health (NIH) have identified a novel class of antibodies that target a previously unexplored region [...]
Surprising Discovery: What If Some Cancer Genes Are Actually Protecting You?
A surprising discovery reveals that a gene previously thought to accelerate esophageal cancer actually helps protect against it initially. This pivotal study could lead to better prediction and prevention strategies tailored to individual genetic [...]
The Cancer Test That Exposes What Conventional Scans Miss
Researchers at UCLA have unveiled startling findings using PSMA-PET imaging that reveal nearly half of patients diagnosed with high-risk prostate cancer might actually have metastases missed by traditional imaging methods. This revelation could profoundly affect future [...]
Pupil size in sleep reveals how memories are processed
Cornell University researchers have found that the pupil is key to understanding how, and when, the brain forms strong, long-lasting memories. By studying mice equipped with brain electrodes and tiny eye-tracking cameras, the researchers [...]
Stanford’s Vaccine Breakthrough Boosts Flu Protection Like Never Before
Stanford Medicine researchers have developed a new method for influenza vaccination that encourages a robust immune response to all four common flu subtypes, potentially increasing the vaccine’s efficacy. In laboratory tests using human tonsil [...]
Water’s Worst Nightmare: The Rise of Superhydrophobic Materials
New materials with near-perfect water repellency offer potential for self-cleaning surfaces in cars and buildings. Scientists from Karlsruhe Institute of Technology (KIT) and the Indian Institute of Technology Guwahati (IITG) have developed a surface [...]
Japanese dentists test drug to help people with missing teeth regrow new ones
Japanese dentists are testing a groundbreaking drug that could enable people with missing teeth to grow new ones, reducing the need for dentures and implants, AFP recently reported. Katsu Takahashi, head of oral surgery at [...]
