Researchers have taken important steps toward creating an antidote and therapeutic for carbon monoxide poisoning. This disabling condition leads to more than 50,000 emergency room visits and 1,500 deaths annually in the United States. To better understand how RcoM works, scientists engineered a new, more effective molecule called RcoM-HBD-CCC. It quickly displaces carbon monoxide in the blood, significantly improving survival and recovery rates of recovering victims.
Carbon monoxide poisoning occurs when this invisible and odorless gas builds up in the blood. It binds to hemoglobin with an affinity that is 200 to 400 times greater than oxygen. The only current treatments have revolved around pumping 100% pure oxygen into their systems, frequently through hyperbaric chambers. As a result, almost 50 percent of individuals who survive carbon monoxide poisoning suffer long-term damage to the heart and brain. The creation of RcoM-HBD-CCC would represent a fundamental change in treatment strategy.
Innovative Development of RcoM-HBD-CCC
The researchers drew inspiration from a natural protein, RcoM, found in the bacterium Paraburkholderia xenovorans, which they modified to produce RcoM-HBD-CCC. This reprogrammed protein has a high affinity for carbon monoxide molecules. It accomplishes this without obstructing oxygen or other important molecules in the body. The creative design focuses on quickly trapping and neutralizing carbon monoxide.
Yet, RcoM-HBD-CCC immediately snatches up CO molecules as soon as it enters the bloodstream. It removes half of a given concentration of the gas from the blood within a minute. Such swift action is in stark contrast to current treatments and positions RcoM-HBD-CCC as a potentially life-saving intervention during time-sensitive emergency situations.
“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.” – Jason J. Rose
Promising Safety Profile
Safety is, rightly so, a huge consideration in any therapeutic development. The early results indicate that RcoM-HBD-CCC will result in modest reductions in blood pressure. This positive result suggests that side effects are less likely than with more standard treatment alternatives. The researchers suspect that RcoM-HBD-CCC scavenges nitric oxide, an important blood-pressure regulating molecule. They believe it accomplishes this at a slower rate than other hemoproteins.
Mark T. Gladwin, one of the researchers behind the study, shared his own optimism about the findings.
“Unlike other protein-based treatments, we found the compound caused only minimal changes in blood pressure, which was an exciting finding and raised the potential for this new molecule to have clinical applications.” – Mark T. Gladwin
The combination of rapid action and minimal side effects makes RcoM-HBD-CCC an attractive candidate for clinical use, particularly in emergency departments where timely intervention is crucial.
Commercializing the Antidote
To further develop RcoM-HBD-CCC, Dr. Rose and Dr. Gladwin co-founded a company, Globin Solutions. To fuel their innovation, they licensed technology based on RcoM from the University of Pittsburgh. Their goal is now to get this novel antidote to market, and get it into the hands of those who need it the most.
The therapeutic landscape for carbon monoxide poisoning hasn’t changed much in the past few decades, so this development is exceptionally interesting. Researchers believe that RcoM-HBD-CCC could be a game-changer due to its ability to “directly and rapidly remove carbon monoxide from the body with such a low risk of off-target side effects.”
“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.” – Jason J. Rose
Our structural study on RcoM-HBD-CCC was recently published in the Proceedings of the National Academy of Sciences (PNAS). It provides an in-depth glimpse into its design while exploring its wide-ranging potential applications.