Hydrogen Gas Therapy Slows ALS Progression and Extends Lifespan in Mice
- Authors
- Yihui Sun, Yingshuai Wang, Qianbo He, Min Zhao, Jiaru Guo, Chunjie Xu, Qiupeng Yan, Yanchun Chen, Bingqiang Zhang, Hongmei Du, Jing Huo, Yong Zhang, Haoyun Zhang, Yingjun Guan, Qianjun He
- Journal
- Acta Biomaterialia
- Year
- 2026
- DOI
- 10.1016/j.actbio.2026.07.004
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Amyotrophic Lateral Sclerosis (ALS)
- Body System
- Nervous System
TL;DR
Sustained hydrogen release from oral Mg₂Si nanosheets slowed disease progression and extended survival in an ALS mouse model.
Key Finding
Oral magnesium-silicon nanosheets that slowly release hydrogen gas delayed ALS progression, improved motor function, and extended lifespan in transgenic mice with the disease.
Summary
Researchers tested a new form of hydrogen therapy in mice with a genetic form of ALS (a disease that damages nerve cells controlling movement). They created special magnesium-silicon particles that release hydrogen gas slowly in the digestive system. In genetically engineered mice with ALS, this treatment slowed disease progression, improved movement, and extended lifespan by reducing harmful molecules called free radicals and calming excessive immune activity in the nervous system.
Practical Takeaway
This is early-stage research in mice only, not humans. While the results are promising for understanding how sustained hydrogen delivery might help ALS, it's far too soon to know if this approach would work in people or be safe for human use. Much more research, including human clinical trials, would be needed before any conclusions could be drawn about practical applications.
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord, with mutant superoxide dismutase 1 (SOD1) induced oxidative stress and neuroinflammation as key pathogenic drivers. Here, we uncover that mutant SOD1 is both a Fenton-like agent able for catalytical generation of ·OH and a hydrogenation catalyst for H2 scavenging reactive oxygen species. To enhance the bioavailability of H2, we develop an orally administered Mg2Si nanosheets based feed for sustained release of high-amount H2. On an ALS model of hSOD1G93A transgenic mice, Mg2Si feed remarkably delays ALS progression, improves the motor performance of ALS mice, and extends their lifespan. Histopathologically, oral Mg2Si treatment ameliorates motor neuron degeneration, misfolded SOD1 aggregation and reactive gliosis in spinal cord, while protecting neuromuscular junctions and ameliorating muscle atrophy during disease progression. Transcriptomic analysis demonstrates the H2-mediated down-regulation of both oxidative stress and neuroinflammatory pathways in response to the suppression of NLRP3 inflammasome activation. The proposed strategy of catalyzed hydrogen therapy offers an inspiration for metalloproteases-related neurodegenerative diseases treatment. STATEMENT OF SIGNIFICANCE: Amyotrophic lateral sclerosis (ALS) is an incurable and devastating neurodegenerative disease lacking effective clinical interventions. Although hydrogen gas (H2) exhibits promising neuroprotective potential, conventional H2 therapy is severely limited by unstable and transient H2 release, failing to sustain long-term treatment requirements for chronic ALS pathogenesis. To overcome this bottleneck, we engineer oral administrable Mg2Si nanosheets that enable sustained H2 release via gastrointestinal retention, achieving stable long-term hydrogen supplementation in vivo. Mechanistically, Mg2Si-derived H2 efficiently eliminates excess free radicals triggered by toxic mutant SOD1, and further disrupts the pathological crosstalk between oxidative stress and neuroinflammation in ALS. In transgenic ALS mice, dietary Mg2Si intervention markedly ameliorates motor dysfunction and effectively delays disease progression. Collectively, this study firstly applies Mg2Si nanomaterial-based sustained hydrogen therapy for ALS treatment, establishes a novel gastrointestinal hydrogen delivery strategy, and provides an innovative and clinically translatable paradigm for the design of hydrogen delivery systems against neurodegenerative disorders.