Pitt team creates protein that reverses CO poisoning in mice

University of Pittsburgh researchers have engineered a protein that can "scavenge" carbon monoxide from the blood and could lead to an antidote for carbon monoxide poisoning. Image: Ronald C. Yochum Jr. CC BY-SA 2.5

There is no true antidote for carbon monoxide poisoning, which accounts for 4,000 hospitalizations and 400 deaths in the U.S. each year. Now University of Pittsburgh researchers have created a molecule that has reversed symptoms in mice and could inspire the first CO poisoning antidote for humans.

A colorless, odorless gas, carbon monoxide is often dubbed the “silent killer.” It replaces oxygen molecules in hemoglobin, so that the blood carries carbon monoxide rather than oxygen to the body’s organs and tissues. CO poisoning can cause dizziness, weakness, chest pain and confusion. Current treatments, such as hyperbaric oxygen therapy or administering 100% oxygen, involve trying to overcome the oxygen shortage in the blood. But these treatments tend to be moderately effective and are not suitable for everyone.

While looking at neuroglobin, a hemoglobin-like protein found in the brain, Dr. Mark Gladwin’s team discovered it had a high affinity for binding to carbon monoxide. They then engineered a new version of the protein that was even better at attaching to CO molecules.

Virtual Roundtable

ESMO Post Show: Highlights From the Virtual Conference

Cancer experts and pharma execs will break down the headline-making data from ESMO, sharing their insights and analysis around the conference’s most closely watched studies. This discussion will examine how groundbreaking research unveiled over the weekend will change clinical practice and prime drugs for key new indications, and panelists will fill you in on the need-to-know takeaways from oncology’s hottest fields.

"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," said Gladwin, a professor of internal medicine at the University of Pittsburgh School of Medicine and director of the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, in the statement.

The team tested the protein, dubbed Ngb H64Q, in mouse models of lethal CO poisoning. Seven out of eight mice that received the treatment survived the experiment, while no more than 10% of subjects in the control group survived. They also found CO bound to the protein in urine, which suggests the animals were able to pass the antidote without toxic side effects.

Because the treated mice had improved levels of oxygen in their tissues, the team inferred that the protein works by “scavenging” CO from hemoglobin and leaving room for oxygen to bind in its place. The mouse models showed the protein to be “significantly better” at removing CO than 100% oxygen treatment.

"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."

Suggested Articles

J&J's EGFR-fighting combo stopped tumor growth in 60% of patients whose lung cancer got worse after taking AstraZeneca's Tagrisso.

Amgen's KRAS inhibitor curbed tumor growth in 88% of patients with non-small cell lung cancer, shrinking tumors in one-third of them.

The trial squeezed under the bar for statistical significance by improving on the median progression-free survival of Zytiga by two months.