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 reveal how exercise protects the brain from Alzheimer’s
Researchers at UC San Francisco have identified a biological process that may explain why exercise sharpens thinking and memory. Their findings suggest that physical activity strengthens the brain's built in defense system, helping protect [...]
NanoMedical Brain/Cloud Interface – Explorations and Implications. A new book from Frank Boehm
New book from Frank Boehm, NanoappsMedical Inc Founder: This book explores the future hypothetical possibility that the cerebral cortex of the human brain might be seamlessly, safely, and securely connected with the Cloud via [...]
Deadly Pancreatic Cancer Found To “Wire Itself” Into the Body’s Nerves
A newly discovered link between pancreatic cancer and neural signaling reveals a promising drug target that slows tumor growth by blocking glutamate uptake. Pancreatic cancer is among the most deadly cancers, and scientists are [...]
This Simple Brain Exercise May Protect Against Dementia for 20 Years
A long-running study following thousands of older adults suggests that a relatively brief period of targeted brain training may have effects that last decades. Starting in the late 1990s, close to 3,000 older adults [...]
Scientists Crack a 50-Year Tissue Mystery With Major Cancer Implications
Researchers have resolved a 50-year-old scientific mystery by identifying the molecular mechanism that allows tissues to regenerate after severe damage. The discovery could help guide future treatments aimed at reducing the risk of cancer [...]
This New Blood Test Can Detect Cancer Before Tumors Appear
A new CRISPR-powered light sensor can detect the faintest whispers of cancer in a single drop of blood. Scientists have created an advanced light-based sensor capable of identifying extremely small amounts of cancer biomarkers [...]
Blindness Breakthrough? This Snail Regrows Eyes in 30 Days
A snail that regrows its eyes may hold the genetic clues to restoring human sight. Human eyes are intricate organs that cannot regrow once damaged. Surprisingly, they share key structural features with the eyes [...]
This Is Why the Same Virus Hits People So Differently
Scientists have mapped how genetics and life experiences leave lasting epigenetic marks on immune cells. The discovery helps explain why people respond so differently to the same infections and could lead to more personalized [...]
Rejuvenating neurons restores learning and memory in mice
EPFL scientists report that briefly switching on three “reprogramming” genes in a small set of memory-trace neurons restored memory in aged mice and in mouse models of Alzheimer’s disease to level of healthy young [...]
New book from Nanoappsmedical Inc. – Global Health Care Equivalency
A new book by Frank Boehm, NanoappsMedical Inc. Founder. This groundbreaking volume explores the vision of a Global Health Care Equivalency (GHCE) system powered by artificial intelligence and quantum computing technologies, operating on secure [...]
New Molecule Blocks Deadliest Brain Cancer at Its Genetic Root
Researchers have identified a molecule that disrupts a critical gene in glioblastoma. Scientists at the UVA Comprehensive Cancer Center say they have found a small molecule that can shut down a gene tied to glioblastoma, a [...]
Scientists Finally Solve a 30-Year-Old Cancer Mystery Hidden in Rye Pollen
Nearly 30 years after rye pollen molecules were shown to slow tumor growth in animals, scientists have finally determined their exact three-dimensional structures. Nearly 30 years ago, researchers noticed something surprising in rye pollen: [...]
How lipid nanoparticles carrying vaccines release their cargo
A study from FAU has shown that lipid nanoparticles restructure their membrane significantly after being absorbed into a cell and ending up in an acidic environment. Vaccines and other medicines are often packed in [...]
New book from NanoappsMedical Inc – Molecular Manufacturing: The Future of Nanomedicine
This book explores the revolutionary potential of atomically precise manufacturing technologies to transform global healthcare, as well as practically every other sector across society. This forward-thinking volume examines how envisaged Factory@Home systems might enable the cost-effective [...]
A Virus Designed in the Lab Could Help Defeat Antibiotic Resistance
Scientists can now design bacteria-killing viruses from DNA, opening a faster path to fighting superbugs. Bacteriophages have been used as treatments for bacterial infections for more than a century. Interest in these viruses is rising [...]
Sleep Deprivation Triggers a Strange Brain Cleanup
When you don’t sleep enough, your brain may clean itself at the exact moment you need it to think. Most people recognize the sensation. After a night of inadequate sleep, staying focused becomes harder [...]
