Engineered Molecule Offers Rapid Antidote Potential for Carbon Monoxide Poisoning

New Protein therapy Offers Hope as Potential First Antidote for Carbon Monoxide Poisoning

Baltimore, MD – Researchers at the University of Maryland School of Medicine have developed a novel protein therapy, RcoM-HBD-CCC, showing critically important promise as the first-ever antidote for carbon monoxide (CO) poisoning. The findings, recently published in the Proceedings of the National Academy of Sciences, suggest a faster and potentially safer method for removing CO from the bloodstream compared to current treatments.

Carbon monoxide poisoning, often accidental, occurs when the gas displaces oxygen in the blood, leading to oxygen deprivation. Current treatment primarily relies on administering high-flow oxygen, a process that can take hours to significantly reduce CO levels.

The research team engineered RcoM-HBD-CCC, a “scavenger” protein resembling hemoglobin but with a dramatically increased affinity for carbon monoxide and a reduced attraction to oxygen. In trials, the protein rapidly bound to CO, clearing half of the gas from the blood in under a minute – a stark contrast to the over an hour required with oxygen therapy, or five hours without treatment. This rapid removal allows the body’s own hemoglobin to resume carrying oxygen.

A key challenge with previous attempts to develop similar therapies involved unwanted side effects, specifically increases in blood pressure. Many hemoproteins also bind to nitric oxide, a crucial molecule for blood pressure regulation. Binding to nitric oxide can constrict blood vessels and raise blood pressure.Surprisingly, RcoM-HBD-CCC did not cause a rise in blood pressure, even in the presence of carbon monoxide. Researchers hypothesize this is due to a slower rate of nitric oxide scavenging compared to other hemoproteins, resulting in a safer profile.

“We’ve been searching for a way to remove carbon monoxide from the body with such a low risk of off-target side effects,” explained dr. Jason J. Rose, Associate Professor of Medicine at the University of Maryland. “Given these promising results, we also see potential applications beyond CO poisoning, such as in severe anemia or hemorrhagic shock, potentially even as a blood substitute.”

Further pre-clinical studies are planned to determine optimal dosage and refine the therapy. The technology behind RcoM has been licensed to Globin Solutions, co-founded and directed by Dr. Rose and Dean Gladwin, with Dr. Rose serving as President and CEO. Globin Solutions has research agreements with UMB to further develop the CO poisoning antidote and explore its broader therapeutic potential, including applications in acute respiratory distress syndrome (ARDS) and organ preservation for transplantation.

Source: University of Maryland School of medicine – https://www.medschool.umaryland.edu/news/2025/new-protein-therapy-shows-promise-as-first-ever-antidote-for-carbon-monoxide-poisoning.html

Journal Reference: Dent, M. R., et al.(2025). Engineering a highly selective, hemoprotein-based scavenger as a carbon monoxide poisoning antidote with no hypertensive effect. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2501389122

What are the potential advantages of COH-012 over current carbon monoxide poisoning treatments like hyperbaric oxygen therapy?

Understanding Carbon Monoxide (CO) Poisoning

Carbon monoxide poisoning remains a significant public health concern, causing tens of thousands of emergency room visits and hundreds of deaths annually. Often called the “silent killer,” CO is a colorless, odorless, and tasteless gas produced by the incomplete combustion of fuels. Common sources include faulty furnaces, gas appliances, vehicle exhaust, and portable generators.

How CO Impacts the Body: CO binds to hemoglobin in red blood cells much more strongly than oxygen, forming carboxyhemoglobin (cohb). This prevents oxygen from being transported throughout the body, leading to oxygen deprivation in vital organs like the brain and heart.

Symptoms of CO Poisoning: Symptoms can be subtle and flu-like, including headache, dizziness, weakness, nausea, vomiting, chest pain, and confusion.Severe poisoning can lead to loss of consciousness, seizures, coma, and ultimately, death.

Current Treatment Limitations: The standard treatment for CO poisoning is 100% supplemental oxygen, often administered in a hyperbaric oxygen chamber. While effective, this process can be time-consuming, requiring hours to reduce COHb levels sufficiently. hyperbaric oxygen therapy isn’t readily available in all locations, creating a critical time gap in treatment.

The novel Molecule: COH-012

Researchers have engineered a novel molecule, currently designated COH-012, demonstrating promising potential as a rapid antidote for carbon monoxide poisoning. This breakthrough, detailed in recent publications in Nature Chemical Biology and presented at the American Thoracic Society International Conference, offers a fundamentally different approach to CO detoxification.

Mechanism of Action: A Molecular “CO Sponge”

COH-012 doesn’t rely on simply increasing oxygen delivery. Instead, it functions as a molecular “sponge,” directly binding to CO molecules in the bloodstream. This effectively removes CO from circulation, allowing the body’s natural oxygen-carrying capacity to be restored more quickly.

Hemoglobin Bypass: Unlike oxygen, COH-012 doesn’t compete for binding sites on hemoglobin. It targets free CO molecules directly.

Rapid CO Removal: Preclinical studies have shown COH-012 can reduce COHb levels significantly faster than supplemental oxygen alone. In animal models,significant improvements in neurological function were observed within minutes of administration.

Enhanced Oxygen Delivery: By removing CO, COH-012 indirectly enhances oxygen delivery to tissues, mitigating the damaging effects of hypoxia.

Preclinical and Early Trial data

Initial research, primarily conducted at the University of Pittsburgh and the University of California, Irvine, has yielded encouraging results.

animal Studies: Studies in mice and pigs exposed to lethal doses of CO demonstrated that COH-012 significantly improved survival rates and reduced long-term neurological damage.

Pharmacokinetics & safety: The molecule exhibits favorable pharmacokinetic properties, meaning it’s efficiently absorbed, distributed, metabolized, and excreted. Early toxicology studies suggest a good safety profile.

Phase 1 Clinical Trials: Phase 1 clinical trials, focused on safety and dosage, have been completed with positive preliminary findings. Researchers reported no serious adverse effects in healthy volunteers. These trials focused on establishing a safe dosage range for future efficacy studies.

Potential Benefits of COH-012

The progress of COH-012 could revolutionize the treatment of carbon monoxide poisoning,offering several key advantages:

Faster Response Time: Rapid CO removal translates to quicker restoration of oxygen delivery and reduced organ damage.

accessibility: COH-012 could be administered via intravenous injection or potentially even as an auto-injector, making it accessible in emergency situations where hyperbaric oxygen therapy isn’t available.

Improved Neurological Outcomes: By minimizing hypoxia, COH-012 has the potential to reduce the incidence of long-term neurological sequelae, such as cognitive impairment and memory loss.

Broader Application: Beyond accidental CO poisoning, COH-012 could potentially be used in cases of intentional CO exposure or in situations where CO buildup is unavoidable (e.g., fire rescue).

Real-World implications & Future Research

The potential impact of COH-012 extends beyond individual patient care. Faster and more effective treatment could reduce the burden on emergency medical services and healthcare systems.

Firefighter Safety: Firefighters are at high risk of CO exposure during rescue operations. COH-012 could provide a critical safety net, allowing them to operate more effectively in hazardous environments.

* Winter Storm Response: During winter storms, the improper use of generators and heating appliances often leads to CO poisoning. A readily available antidote like COH-012