New remedy for carbon monoxide poisoning

Hemoglobin-like protein absorbs carbon monoxide from the blood

Promising antidote: Carbon monoxide poisoning can be fatal – and so far, it can only be treated in hyperbaric chambers. But a newly developed protein could help treat CO poisoning more easily, quickly, and effectively. The new designer protein is based on a bacterial model, resembles our blood hemoglobin, and, unlike previous approaches, has no side effects.

The natural protein RcoM served as a template for the designer protein. © University of Maryland School of Medicine

Carbon monoxide (CO) is released, among other things, when combustion occurs in a lack of oxygen. Anyone who inhales the invisible and odorless gas through smoke can suffer severe carbon monoxide poisoning. Around 30,000 people worldwide die annually from this type of smoke poisoning, particularly in fires in enclosed spaces. But incorrectly connected fireplaces and the operation of cars, generators, and hookahs in poorly ventilated rooms can also lead to a life-threatening accumulation of carbon monoxide in the air we breathe.

How is carbon monoxide poisoning treated?

The dangerous thing about it: After inhalation, carbon monoxide binds with high affinity to the red hemoglobin molecules in our blood. These molecules are actually responsible for transporting oxygen and carbon dioxide (CO2) in the body, but bind up to 400 times more strongly to carbon monoxide. This blocks the absorption and transport of vital oxygen. As a result, organs and tissues are no longer adequately supplied with oxygen – those affected slowly suffocate internally.

To treat CO poisoning, the affected person's body is currently flooded with pure oxygen. Due to their excessive presence, the oxygen molecules then displace the toxic CO gas from the hemoglobin molecules in the blood. This washout is accelerated by increased pressure in a hyperbaric chamber, which, however, first requires ambulance transport to facilities with such chambers. For many people, treatment therefore comes too late, and even survivors often suffer permanent heart and brain damage due to the temporary lack of oxygen.

Seeking a Better Therapy

A team led by Matthew Dent from the University of Pittsburgh therefore searched for a way to more quickly remove carbon monoxide from the hemoglobin in the blood of poisoning victims. To this end, they developed a protein that can be injected into the affected individuals. In their blood, it can then absorb carbon monoxide like a sponge and bind the gas with even greater affinity than hemoglobin.

The researchers used a natural hemoprotein called RcoM, which is produced by the bacterium Paraburkholderia xenovorans. In the microbe, the protein RcoM, which is related to our hemoglobin, acts as a natural CO sensor. Dent and his colleagues have now modified and shortened this protein in the laboratory so that it binds even more selectively to carbon monoxide – without simultaneously absorbing oxygen or other gas molecules. They called this designer protein RcoM-HBD-CCC and tested its effectiveness in mice.

Graphic shows how carbon monoxide (CO) travels from the air we breathe to the hemoglobin in the blood.© University of Maryland School of Medicine

Hemodialysis in less than a minute

The result: The protein takes less than a minute to remove half of all carbon monoxide molecules from the animals' blood. Conventional oxygen therapy takes 74 minutes in humans, and 30 minutes with a pressure chamber. The designer protein absorbs the carbon monoxide molecules from the hemoglobins and transports them via the blood to the kidneys. There, the CO-protein complexes are excreted in the urine. The released hemoglobin molecules in the blood can then bind oxygen again, as the mouse experiments showed.

"This protein has the potential to become a rapid, intravenous antidote to carbon monoxide. It could be administered in the emergency room or even on-site by first responders," says senior author Mark Gladwin of the University of Maryland in Baltimore.

Little Side Effect on Blood Pressure

A few years ago, Gladwin's team developed a similar designer protein: Ngb-H64Q-CCC. Its disadvantage: In addition to CO, it also binds strongly to nitric oxide (NO). This gas regulates blood pressure. When there is little NO circulating in the blood, blood vessels constrict and blood pressure rises. This would be an undesirable side effect for a potential CO antivenom.

One concern of the researchers was therefore that the new designer hemoprotein RcoM-HBD-CCC might also bind nitric oxide. However, the team found that the animals injected with this protein showed only minimal fluctuations in blood pressure. This suggests that RcoM-HBD-CCC binds very little nitric oxide or only so slowly that it has no serious effects on blood pressure.

"Could be a game changer"

"This molecule could be a game changer because it can directly and rapidly remove carbon monoxide from the body with such a low risk of side effects," says co-author Jason Rose of the University of Maryland. "Given the promising results, we also see the potential for the use of RcoM-HBD-CCC in other areas, for example, as a blood substitute for severe anemia or hemorrhagic shock." The protein would also replace the function of our natural hemoglobin in this case.

The researchers have already founded a company that holds the license for this technology and could produce the newly developed protein as a CO antidote in the future. Before the protein can actually be used as an antidote for carbon monoxide poisoning or other therapies, however, it must first be further tested on animals. If its safety is confirmed, clinical trials with humans would follow. (Proceedings of the National Academy of Sciences, 2025; doi: 10.1073/pnas.2501389122)

Source: University of Maryland School of Medicine