Carbon monoxide is often called the “silent killer.” Each year, about 50,000 Americans end up in emergency rooms after exposure to this invisible gas, and roughly 1,500 die. The tragedy is that treatment hasn’t changed much in decades: doctors administer oxygen, sometimes in high-pressure chambers, and hope patients recover. Yet nearly half of survivors suffer long-term brain or heart damage.

Now, a team from the University of Maryland School of Medicine, the University of Pittsburgh, and Wake Forest University has engineered a molecule that could change this grim reality. Their protein-based antidote, called RcoM-HBD-CCC, rapidly pulls carbon monoxide (CO) out of the bloodstream and, unlike earlier attempts, does so without spiking blood pressure, a common and dangerous side effect.

How It Works

The therapy is inspired by a bacterium, Paraburkholderia xenovorans, that naturally senses CO in its environment. The bacterial protein it uses for this, known as RcoM (short for “regulator of CO metabolism”), is incredibly sensitive to trace amounts of the gas.

Scientists trimmed and re-engineered the protein into a compact form, RcoM-HBD-CCC, that binds to CO with extreme stickiness — nearly 50 times stronger than hemoglobin. Hemoglobin in our red blood cells normally carries oxygen but will also bind to CO which uses up precious storage. But the selectivity of RcoM-HBD-CCC for CO over oxygen is so high that it acts like a molecular sponge, pulling CO off hemoglobin and freeing red blood cells to carry oxygen again.

In mice, the antidote worked within minutes. After CO exposure of the mice, the gas cleared from the blood of treated animals far faster than untreated ones. Even more promising, the protein then flushed harmlessly out of the body through urine.

“This has the potential to become a rapid, intravenous antidote for carbon monoxide that could be given in the emergency department or even in the field by first-responders,” said study author Mark T. Gladwin, who is the Dean of the University of Maryland School of Medicine (UMSOM).

Why It’s Different

Attempts to design CO scavengers in the past have run into trouble. Many engineered proteins, while good at trapping carbon monoxide, also bind to nitric oxide — a molecule that regulates blood pressure. That unintended side effect can cause dangerous spikes in blood pressure, kidney damage, or worse.

But RcoM-HBD-CCC seems to avoid this problem. Laboratory tests showed that it reacts with nitric oxide much more slowly than other protein therapies. In mice, even at high doses, it caused no hypertension and no organ damage.

“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 off-target side effects,” said Jason J. Rose, Associate Professor of Medicine at UMSOM.

The team’s data show why. CO binds so tightly to the engineered protein that it rarely escapes. In fact, CO’s half-life inside the protein is measured in days, compared to minutes for oxygen. That one-way binding explains its potency.

What Comes Next

So far, the therapy has only been tested in mice. Human trials remain years away, and many questions need answers. What is the right dose? Could the protein work in severely poisoned patients where damage is already underway? And how will regulators evaluate a drug that’s meant for emergencies, not daily use?

The potential uses also go beyond poisoning. Rose points out that similar molecules might one day serve as blood substitutes for people with severe anemia or blood loss, or even help preserve organs before transplant.

Still, the biggest prize is an actual antidote for carbon monoxide. For decades, emergency medicine has relied on oxygen tanks and hyperbaric chambers. If RcoM-HBD-CCC lives up to its promise, it could give doctors and first responders a tool that works in minutes, not hours.

The findings appeared in the Proceedings of the National Academy of Sciences.