When cocaine is used for recreational purposes, cocaine toxicity is very common. In fact, visits to emergency rooms every year number in the half a million range to treat this condition. As this rate continues to grow, there is still no Food and Drug Administration-approved pharmacotherapy designed specifically to treat cocaine toxicity.

In a recent Science Daily release, it was reported that researchers have successfully developed and tested a modified enzyme that has the ability to break down cocaine into inactive products nearly 1,000 times faster than the human body has the ability to do. CocE is an engineered enzyme that could be considered a candidate for clinical use.

It has been difficult to design a therapy for cocaine toxicity simply because of the complex mechanisms of actions inherent in cocaine. The drug can block multiple targets in the brain and body, producing cardiovascular and anesthetic effects. It also has strong addictive properties. At the same time, many of the metabolites of cocaine that the body will form can have similar and sometimes even stronger effects than the cocaine itself.

The potential of cocaine esterase (CocE) to block cocaine toxicity by eliminating cocaine has been studied by Remy L. Brim and colleagues at the University of Michigan, in collaboration with Columbia University and the University of Kentucky. CocE is an enzyme that was originally isolated from a soil bacterium found around the roots of the coca plant.

The challenge is that CocE is naturally unstable at the normal body temperature of 37°C. The investigators used a series of biochemical and computational approaches for modification in an effort to enhance the thermal stability of the enzyme. When thermally stable, CocE can effectively degrade cocaine and two of its active metabolites without degrading benzoylecgonine, which is used in urinalyses for recent cocaine use.