University of Pittsburgh and University of Maryland researchers have developed a novel antidote for carbon monoxide (CO) poisoning – an immobilized engineered hemeprotein bound to an agarose resin. This activated resin can efficiently remove CO from blood extracorporeally like a dialysis machine. The approach could pave the way for more efficient CO removal from blood, eliminating the need for intravenous infusion of heme-based molecular scavengers and reducing the risks of heme toxicity.
Binding of an engineered hemeprotein, Ngb-H64Q-CCC, can produce a filter to remove CO from blood following poisoning. This novel extracorporeal approach could be a safer and more accessible method to treat CO-poisoning essentially acting as an antidote.
Description
CO gas is colorless, tasteless, and odorless and produced from incomplete combustion of fuels like natural gas, oil, and coal. CO poisoning accounts for close to 50,000 emergency department visits each year in the US alone and nearly 30,000 deaths per year globally. CO poisoning disrupts the transport of oxygen around the body due to the strong binding affinity of CO to hemoglobin, leading to hypoxia and long-term health effects including cardiac and neurological complications. Currently, no antidote for CO poisoning exists and there is a clinical need to develop less-toxic treatments for victims of CO poisoning. This novel scavenger hemeprotein is designed to extracorporeally remove CO from the hemoglobin and could prove to be an accessible, low-risk alternative to current CO treatment strategies.
Applications
• Carbon monoxide poisoning
Advantages
Current treatment for severe CO poisoning involves either hyperbaric oxygen therapy, not always readily available, or an intravenous infusion of a large amount of heme-based scavenger molecules (20–100 g) to decrease blood CO levels. However, heme is a known toxin and release of heme can cause liver and kidney damage. Recently, an engineered heme protein, Ngb-H64Q-CCC was developed and while infusion improved survival in a lethal CO-poisoning animal model, toxicity risks persist.
This novel approach immobilizes Ngb-H64Q-CCC using an agarose-based matrix. This immobilized resin can be adapted for use in an existing extracorporeal device (e.g., ECCO2R) to remove CO without any need for an infusion and removing the risk of organ toxicity. Additionally, the resin is stable (>75 days) and regenerated after use, time and time again.
Invention Readiness
Ngb-H64Q-CCC was immobilized using an activated agarose resin to produce a filter compound. Testing confirmed this compound could remove CO from a solution of CO-bound hemoglobin. The filter could be reactivated after use and was stable with no loss of scavenging activity observed over 75 days. Optimization of this approach and development of cartridges containing the filter for use in existing ECCO2R systems is needed, as well as animal and human trials.
IP Status
Patent Pending
