U.S. researchers develop 1st potential antidote for carbon monoxide poisoning

U.S. researchers on Wednesday reported engineering a protein that rapidly reverses carbon monoxide (CO) poisoning in mice, a discovery that could potentially lead to the first antidote to this common "silent killer" in humans.

A toxic byproduct of burning fuel in cars, stoves, and other engines, CO is one of the leading causes of poisoning death worldwide, sending about 50,000 people to the emergency room each year in the U.S. alone.

The colorless and odorless gas sticks to hemoglobin, which carries oxygen in red blood cells, preventing oxygen from reaching vital organs.

"Despite being the most common poisoning worldwide, we still do not have an effective antidote for CO exposure," Professor Mark Gladwin of University of Pittsburgh School of Medicine, who led the study, said in a statement.

"Our protein is extraordinarily effective at scavenging CO from the blood, and could potentially prove to be a significant advance in the treatment of CO poisoning."

Current treatment options for CO poisoning -- administering 100 percent oxygen or using a pressurized hyperbaric chamber to administer oxygen at greater than normal air pressure -- focus on trying to replace CO in blood with oxygen as quickly as possible, but both are only moderately effective, according to the study published in the U.S. journal Science Translational Medicine.

Gladwin and colleagues turned to a hemoglobin-like protein found in the brain called neuroglobin, which they found could bind CO with an unusually high affinity.

The researchers tweaked the molecule to generate a mutant version called Ngb H64Q, that was an even better scavenger of CO.

When tested in mice of non-lethal CO poisoning, they found that Ngb H64Q was significantly better at removing CO from hemoglobin than 100-percent oxygen treatment.

The normal half-life of CO in humans after poisoning, the time it takes for half of the CO to be eliminated from the body, is 320 minutes, and even with 100-percent oxygen therapy, that time is 74 minutes. With the antidote therapy, the CO half-life was reduced to only 23 seconds, they said.

In mice with lethal levels of CO poisoning, seven out of eight mice treated with Ngb H64Q survived the duration of the experiment, while 10 percent or less survived in the control groups.

Additionally, the antidote restored heart rate and blood pressure to normal.

Importantly, CO bound to Ngb H64Q was detected in the urine of mice shortly after treatment, which indicated that the rodents were able to excrete the antidote from the body without any major toxic effects.

"If approved, this antidote could be rapidly administered to victims in the field, eliminating costly delays that occur with current treatment options," Gladwin said. "We still need extensive safety and efficacy testing before an antidote is available on the shelf, but our early results are very promising." Enditem