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
Unlocking hidden soil microbes for new antibiotics
Most bacteria cannot be cultured in the lab-and that's been bad news for medicine. Many of our frontline antibiotics originated from microbes, yet as antibiotic resistance spreads and drug pipelines run dry, the soil [...]
By working together, cells can extend their senses beyond their direct environment
The story of the princess and the pea evokes an image of a highly sensitive young royal woman so refined, she can sense a pea under a stack of mattresses. When it comes to [...]
Overworked Brain Cells May Hold the Key to Parkinson’s
Scientists at Gladstone Institutes uncovered a surprising reason why dopamine-producing neurons, crucial for smooth body movements, die in Parkinson’s disease. In mice, when these neurons were kept overactive for weeks, they began to falter, [...]
Old tires find new life: Rubber particles strengthen superhydrophobic coatings against corrosion
Development of highly robust superhydrophobic anti-corrosion coating using recycled tire rubber particles. Superhydrophobic materials offer a strategy for developing marine anti-corrosion materials due to their low solid-liquid contact area and low surface energy. However, [...]
This implant could soon allow you to read minds
Mind reading: Long a science fiction fantasy, today an increasingly concrete scientific goal. Researchers at Stanford University have succeeded in decoding internal language in real time thanks to a brain implant and artificial intelligence. [...]
A New Weapon Against Cancer: Cold Plasma Destroys Hidden Tumor Cells
Cold plasma penetrates deep into tumors and attacks cancer cells. Short-lived molecules were identified as key drivers. Scientists at the Leibniz Institute for Plasma Science and Technology (INP), working with colleagues from Greifswald University Hospital and [...]
This Common Sleep Aid May Also Protect Your Brain From Alzheimer’s
Lemborexant and similar sleep medications show potential for treating tau-related disorders, including Alzheimer’s disease. New research from Washington University School of Medicine in St. Louis shows that a commonly used sleep medication can restore normal sleep patterns and [...]
Sugar-Coated Nanoparticles Boost Cancer Drug Efficacy
A team of researchers at the University of Mississippi has discovered that coating cancer treatment carrying nanoparticles in a sugar-like material increases their treatment efficacy. They reported their findings in Advanced Healthcare Materials. Over a tenth of breast [...]
Nanoparticle-Based Vaccine Shows Promise in Fighting Cancer
In a study published in OncoImmunology, researchers from the German Cancer Research Center and Heidelberg University have created a therapeutic vaccine that mobilizes the immune system to target cancer cells. The researchers demonstrated that virus peptides combined [...]
Quantitative imaging method reveals how cells rapidly sort and transport lipids
Lipids are difficult to detect with light microscopy. Using a new chemical labeling strategy, a Dresden-based team led by André Nadler at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) and [...]
Ancient DNA reveals cause of world’s first recorded pandemic
Scientists have confirmed that the Justinian Plague, the world’s first recorded pandemic, was caused by Yersinia pestis, the same bacterium behind the Black Death. Dating back some 1,500 years and long described in historical texts but [...]
“AI Is Not Intelligent at All” – Expert Warns of Worldwide Threat to Human Dignity
Opaque AI systems risk undermining human rights and dignity. Global cooperation is needed to ensure protection. The rise of artificial intelligence (AI) has changed how people interact, but it also poses a global risk to human [...]
Nanomotors: Where Are They Now?
First introduced in 2004, nanomotors have steadily advanced from a scientific curiosity to a practical technology with wide-ranging applications. This article explores the key developments, recent innovations, and major uses of nanomotors today. A [...]
Study Finds 95% of Tested Beers Contain Toxic “Forever Chemicals”
Researchers found PFAS in 95% of tested beers, with the highest levels linked to contaminated local water sources. Per- and polyfluoroalkyl substances (PFAS), better known as forever chemicals, are gaining notoriety for their ability [...]
Long COVID Symptoms Are Closer To A Stroke Or Parkinson’s Disease Than Fatigue
When most people get sick with COVID-19 today, they think of it as a brief illness, similar to a cold. However, for a large number of people, the illness doesn't end there. The World [...]
The world’s first AI Hospital, developed in China is transforming healthcare
Artificial Intelligence and its developments have had a revolutionary impact on society, and healthcare is not an exception. China has made massive strides in AI integrated healthcare, and continues to do so as AI [...]
