In a groundbreaking advance poised to redefine emergency treatment for carbon monoxide poisoning, researchers from the University of Maryland School of Medicine (UMSOM) have engineered a novel protein-based antidote that selectively targets and removes carbon monoxide (CO) from the bloodstream with unprecedented speed and safety. This innovation is detailed in a recent study published in Proceedings of the National Academy of Sciences (PNAS) and represents a critical leap toward more effective therapies for a condition that annually causes thousands of emergency visits and fatalities worldwide.
Carbon monoxide poisoning poses a formidable health threat due to the gas’s high affinity for hemoglobin, the oxygen-carrying protein in red blood cells. Unlike oxygen molecules, CO binds to hemoglobin with an affinity 200 to 400 times stronger, effectively displacing oxygen and starving tissues of this vital molecule. This displacement can lead to irreversible damage in the brain and heart, underscoring the urgent need for treatments that rapidly restore oxygen delivery before lasting injury occurs.
Current standard-of-care therapies for CO poisoning rely heavily on oxygen administration—either at normal atmospheric levels or employing hyperbaric oxygen chambers to accelerate CO dissociation from hemoglobin. While helpful, these approaches often fall short in clinical effectiveness, especially if diagnosis and treatment initiation are delayed. Even with oxygen therapy, approximately half of poisoned patients suffer chronic neurological and cardiac complications, revealing a clear gap for therapeutic innovation.
The UMSOM team, led by Dr. Mark T. Gladwin and Dr. Jason J. Rose, focused on a bioengineered solution inspired by a natural bacterial protein known as RcoM, a regulator of metabolism in Paraburkholderia xenovorans. This protein naturally senses trace carbon monoxide, allowing the bacteria to respond to environmental CO levels. Harnessing this biological specificity, the researchers created an enhanced version dubbed RcoM-HBD-CCC, engineered to act as a molecular sponge that binds CO in the bloodstream with remarkable selectivity and minimal interaction with oxygen or other critical molecules.
Experimental studies conducted in murine models revealed that RcoM-HBD-CCC could clear carbon monoxide from red blood cells in under a minute, drastically outpacing the hours-long clearance times observed with pure oxygen therapy. This rapid scavenging is achieved without interfering with oxygen binding, allowing hemoglobin molecules to resume their vital role of oxygen transport far sooner. Additionally, the compound demonstrated efficient renal clearance, exiting the body through urine, which mitigates risks of accumulation and toxicity.
The therapeutic promise of RcoM-HBD-CCC is further underscored by its favorable hemodynamic profile. Unlike previous hemoprotein-based scavengers, which inadvertently scavenge nitric oxide (NO) and cause dangerous spikes in blood pressure, this engineered protein exhibited negligible hypertensive effects in animal models. The authors hypothesize that although RcoM-HBD-CCC may interact with nitric oxide, it does so at a rate and affinity that preserve normal vascular tone, reducing common side effects that have hampered clinical application of similar compounds.
Mechanistically, carbon monoxide’s toxicity arises from its binding to hemoglobin’s heme iron centers, forming carboxyhemoglobin, which is incapable of oxygen transport. By introducing a high-affinity hemoprotein that preferentially steels CO molecules away from hemoglobin, RcoM-HBD-CCC effectively re-establishes oxygen delivery pathways at the molecular level. This direct removal strategy contrasts with oxygen therapies that merely push the equilibrium toward dissociation but do not actively scavenge CO.
Beyond its immediate use as an antidote, this novel hemoprotein scaffold offers exciting possibilities in other clinical arenas. The research team envisions applications in blood substitution therapies, especially in critical conditions like severe anemia or hemorrhagic shock, where oxygen delivery is compromised. Moreover, there is potential for its use in acute respiratory distress syndrome (ARDS) and in the preservation of donor organs, where oxygen transport and nitric oxide balance are critical factors.
The development of RcoM-HBD-CCC aligns with a broader trend in biomedical engineering: the repurposing and refinement of natural proteins to meet therapeutic challenges. By starting with a naturally evolved, CO-sensing protein and employing sophisticated protein engineering techniques to optimize its binding characteristics and pharmacokinetics, the researchers have exemplified a model of precision bioengineering that balances efficacy with safety.
Although promising, translation from murine models to human clinical use will require extensive pre-clinical and clinical testing to elucidate optimal dosing, safety margins, and long-term effects. The research group acknowledges that dose-ranging studies will be crucial to ensure the protein’s efficacy without off-target effects, especially considering the complex interplay of hemoproteins with vascular signaling molecules like nitric oxide.
The impact of this research is amplified by the involvement of Globin Solutions, a biotechnology company co-founded by Drs. Rose and Gladwin. Commercial development efforts are underway based on patents licensed from the University of Pittsburgh, aiming to bring this innovation out of the laboratory and into emergency medical practice. The accessibility of a rapid, intravenous antidote for carbon monoxide poisoning could revolutionize frontline responses, enabling administration in ambulances or emergency departments, thereby reducing morbidity and mortality substantially.
Carbon monoxide poisoning remains a pervasive health hazard, often resulting from environmental exposures such as indoor combustion appliances, power generators operated in poorly ventilated spaces, or smoke inhalation during fires. Efforts to reduce exposure risk have met limited success, thus amplifying the necessity for improved medical responses. RcoM-HBD-CCC addresses this need by providing a molecular tool designed for speed and specificity, traits essential in the acute clinical context where every minute counts.
In summary, this engineered hemoprotein represents a landmark innovation that merges microbial biochemistry with clinical medicine, offering a blueprint for future antidotes that directly neutralize toxins in vivo. Its high affinity for carbon monoxide, favorable safety profile, and rapid clearance from the body together suggest a transformative solution to a longstanding medical challenge. As development proceeds, RcoM-HBD-CCC could soon redefine the standard of care for carbon monoxide poisoning, preserving lives and reducing the global burden of this insidious poison.
Subject of Research: Animals
Article Title: Engineering a highly selective, hemoprotein-based scavenger as a carbon monoxide poisoning antidote with no hypertensive effect
News Publication Date: 5-Aug-2025
Web References:
- https://www.pnas.org/doi/10.1073/pnas.2501389122
- https://www.medschool.umaryland.edu/profiles/gladwin-mark/
- https://www.medschool.umaryland.edu/profiles/rose-jason/
References:
Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2501389122
Image Credits: University of Maryland School of Medicine
Keywords: Toxicology, Emergency Medicine
