Scientists at the University of Pittsburgh said they have discovered a promising possible antidote for one of the most common causes of poisoning death in the United States: carbon monoxide.
“If you have a snake bite, there’s an antidote for the venom. If you have cyanide poisoning, we have antidotes,” said Mark Gladwin, chair of medicine at the Pitt School of Medicine and director of the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute. “But carbon monoxide poisoning … there’s no antidote.”
Carbon monoxide is a colorless, odorless gas that causes more than 400 deaths in the United States each year, according to the Centers for Disease Control. It is among the top causes of poisoning deaths, and men are more than three times as likely to die from carbon monoxide poisoning than women. Carbon monoxide can be emitted by appliances that burn gas, wood or kerosene.
Gladwin said it was serendipity that led to the discovery of the potential antidote. During summer 2013, his lab was working with various molecules that are similar to hemoglobin, the molecule in red blood cells that carries oxygen from the lungs to the rest of the body. They had recently found that neuroglobin, a protein in the nervous system, was also incredibly efficient at carrying oxygen molecules.
Around the same time, Gladwin had seen several patients with carbon monoxide, or CO, poisoning.
“A colleague had asked me, ‘Is there an antidote for CO poisoning?’ and that started me thinking, those two events, about how to develop an antidote,” Gladwin said. “About three days later, it struck me that we had this molecule that bound oxygen really tightly, and I thought maybe it will bind CO really tightly.”
Carbon monoxide poisoning occurs when CO molecules are picked up by the hemoglobin, displacing oxygen molecules, which can lead to brain and tissue damage. Gladwin then set out to see how well neuroglobin could capture carbon monoxide molecules.
“We were really lucky because (neuroglobin) ends up having one of the highest carbon monoxide affinities of any known molecule,” Gladwin said. “It’s just a really an avid CO scavenger.”
In experiments with mice, Gladwin and his team found that once neuroglobin was introduced, half of the CO molecules were cleared from the bloodstream in about 25 seconds and from the body entirely, via the kidneys and bladder, in about 13 minutes. The typical half-life of CO in the bloodstream is nearly five-and-a-half hours.
“When we give this molecule, it essentially sops up all the CO in the body, it binds all the CO in the body and that frees up the hemoglobin to carry oxygen,” he said.
Gladwin said current therapies involve giving 100 percent oxygen and immersing a patient in a hyperbaric chamber, a pressurized environment which causes oxygen to dissolve directly into tissues, bypassing the blocked hemoglobin in the bloodstream. But he said hyperbaric oxygen therapy only reduces the half-life of CO in the bloodstream to 20 minutes, and also requires transport to a hospital.
Gladwin said he envisions a future when a CO poisoning antidote can be administered on the spot by emergency medical personnel ahead of transport to the hospital.
Though experiments showed the mice experienced no adverse effects from the short-term CO poisoning and neuroglobin therapy, Gladwin said the next step will be to demonstrate the safety of the antidote in rats or larger mammals, before moving on to human trials.
A paper detailing the discovery was published Wednesday in the journal Science Translational Medicine.
