Cure for carbon monoxide poisoning

11 December 2016

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A breakthrough therapy to rescue the tens of thousands of people killed or injured each year by carbon monoxide poisoning has been developed by scientists in the US.

Carbon monoxide is a colourless, odourless gas present in car exhausts and boiler flues. It's toxic because it binds tightly to haemoglobin in the blood and prevents it from delivering oxygen to our tissues.

Vulnerable organs, like the brain and heart, can suffer irreversible and often fatal damage owing to oxygen deprivation. Currently, the only therapy for the thousands of people poisoned each year is oxygen therapy, which can slowly drive off the carbon monoxide and restore oxygen levels in the tissues.

Sadly, this often comes too late for many victims, largely because it requires specialist facilities that are long distances away. Now a team at the University of Pittsburgh led by Mark Gladwin have developed an injectable molecule that loosens carbon monoxide's grip on our haemoglobin and allows the kidneys to dispose of it safely.

The new molecule is a modified form of a chemical found in the brain called "neuroglobin". This is a haemoglobin-like chemical used by nerve cells to defend themselves against biochemical stress and low oxygen levels.

Searching for a better understanding of its actions, Gladwin and his team switched a handful of the amino acid building blocks that form part of the neuroglobin protein. The resulting molecule turns out to be a chemical rottweiler that binds carbon monoxide 500 times more powerfully than haemoglobin.

Added to carbon monoxide poisoned red blood cells, the modified neuroglobin tears off the carbon monoxide and restores the haemoglobin to its former state within seconds. Normally it would take hours for carbon monoxide to relinquish its hold.

The results were so impressive that the Pittsburgh team then tried injecting the new molecule directly into mice suffering from carbon monoxide exposure. Compared with control animals, the treated mice all survived and there were no obvious signs of biochemical damage.

Measurements show that, once the modified neuroglobin sequesters a carbon monoxide molecule, it reverts to a form that can be filtered rapidly into the urine by the kidney and then exits the body harmlessly.

According to Gladwin, an intervention like this could be deployed aboard ambulances and with fire crews so that victims of carbon monoxide poisoning could receive rapid "at the scene" therapy, dramatically cutting the treatment times and improving outcomes. That said, he also acknowledges that a mouse is not a person, and they haven't yet determined whether their mice nevertheless still suffer brain damage despite receiving the treatment, so there's still work to be done...

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