The treatment for carbon monoxide poisoning can change significantly with the advent of new ligand-trap antidote, five-coordinate H64Q neuroglobin. This mutated molecule, by their virtue of high CO binding affinity, can bind and eliminate CO from blood.
Carbon monoxide (CO) poisoning is a major contributor to poisoning-related deaths worldwide. Severe CO poisoning can cause lactic acidosis, hemodynamic instability, and respiratory failure. There is no known antidote for CO-related incidents, and their treatments have remained the same since the 19th century. Currently, the patients of CO poisoning are treated using supplemental oxygen therapies. In some acute cases, these therapies are not effective. There is a need for a strong antidote for CO poisoning.
Carbon monoxide, upon entering the blood stream, bonds substantially with the hemoglobin (Hb). In order to reverse this bonding, the ideal antidote needs to have a higher affinity to bind with CO. Researchers have engineered a mutant neuroglobin (Ngb) that can serve this purpose. The research article on this study can be found in the Science Translational Medicine journal published in December 2016.
The researchers analyzed the requirements for an antidote and engineered a new compound, a five coordinate neuroglobin (Ngb-H64Q-CCC), from naturally occurring human Neuroglobin. This compound displayed a high affinity and higher bonding rate to CO, making it an ideal antidote. In order to observe the reaction in vivo, researchers exposed 6 male mice to a non-lethal dose of CO, which steadily increased systemic CO-Hb levels in the mice. They then infused a dosage of Ngb-H64Q-CCC immediately after stopping the CO exposure. Blood tests conducted over intervals of every 5 minutes showed that the CO-Hb levels decreased rapidly upon the infusion of Ngb-H64Q-CCC. The new compound could rapidly bind with, and remove, the CO from the blood stream.
Results from the study show a positive indication for the use of mutated neuroglobins as an antidote to carbon monoxide poisoning. The fast-acting, effective and safe compound developed in this study can be further clinically tested on large mammals and then humans to be further validated. The study has made a significant break-through in the treatment of carbon monoxide poisoning.
Written By: Anuja Kulkami, Biomedical Engineer