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
Scientists Unlock a New Way to Hear the Brain’s Hidden Language
Scientists can finally hear the brain’s quietest messages—unlocking the hidden code behind how neurons think, decide, and remember. Scientists have created a new protein that can capture the incoming chemical signals received by brain [...]
Does being infected or vaccinated first influence COVID-19 immunity?
A new study analyzing the immune response to COVID-19 in a Catalan cohort of health workers sheds light on an important question: does it matter whether a person was first infected or first vaccinated? [...]
We May Never Know if AI Is Conscious, Says Cambridge Philosopher
As claims about conscious AI grow louder, a Cambridge philosopher argues that we lack the evidence to know whether machines can truly be conscious, let alone morally significant. A philosopher at the University of [...]
AI Helped Scientists Stop a Virus With One Tiny Change
Using AI, researchers identified one tiny molecular interaction that viruses need to infect cells. Disrupting it stopped the virus before infection could begin. Washington State University scientists have uncovered a method to interfere with a key [...]
Deadly Hospital Fungus May Finally Have a Weakness
A deadly, drug-resistant hospital fungus may finally have a weakness—and scientists think they’ve found it. Researchers have identified a genetic process that could open the door to new treatments for a dangerous fungal infection [...]
Fever-Proof Bird Flu Variant Could Fuel the Next Pandemic
Bird flu viruses present a significant risk to humans because they can continue replicating at temperatures higher than a typical fever. Fever is one of the body’s main tools for slowing or stopping viral [...]
What could the future of nanoscience look like?
Society has a lot to thank for nanoscience. From improved health monitoring to reducing the size of electronics, scientists’ ability to delve deeper and better understand chemistry at the nanoscale has opened up numerous [...]
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
