Cracking Cocaine

 

Cocaine is a powerful nervous system stimulant that, according to Wikipedia, has a wide variety of different effects than can last for anywhere between 15 minutes to an hour. It is also quite addictive and getting addicted to something, whether it be drugs, alcohol or Game of Thrones, can be harmful to someone’s health. Often because it can lead to overdosing (‘OD-ing’).

Scientists have been working on ways to counter the addictive properties of drugs and to prevent people overdosing. In a paper published in Chemical Biology a team of researchers may have come up with a way to do just that.

Researchers from the University of Kentucky altered a naturally occurring enzyme (a large protein molecule) that breaks down called ‘Cocaine esterase’ (CocE). To be more precise, CoCE is a catalyst, meaning that it causes and accelerates a reaction , which results in cocaine being broken down.

Cocaine esterase is produced by bacteria living in the soil around coca plants (where cocaine comes from). Scientists have been investigating this protein as a possible candidate for cocaine addiction therapy for a while. However, it is very unstable in the human body and stops working in just under 12 minutes, making it all but useless for treating addicts.

But the alterations the University of Kentucky researchers made to CocE improved its stability in the body and its catalytic efficiency, which has led them to believe that this enzyme could potentially be applied as an emergency treatment for cocaine overdose and possibly even for cocaine addiction.

The first batch of alterations, made in 2009, showed that two specific mutations introduced into the CocE enzyme extended its ‘half-life’ (the time it takes for the activity of the enzyme to reduce by half) to around 6 hours. This could possibly be long enough to neutralize the effects of the drug in someone experiencing an cocaine overdose.

Unfortunately, this isn’t enough time to be effective as a potential treatment for addiction. To treat addiction, CocE would need to stay in the body for days, preferably weeks, thus preventing the user from getting high at all and weaning them off cocaine, slowly and steadily.

The researchers ran computer simulations to model which parts of the enzyme were most affected by high temperatures and then made further alterations to those areas. These models revealed that with just two more alterations – specifically, swapping the amino acids lysine and isoleucine for cysteine – stabilized the structure of the enzyme.

The CocE enzyme’s half-life at body temperature was extended to over 100 days. Furthermore, the catalytic efficiency against cocaine was increased by about 150%.

The team then employed a method used in drug design to increase the amount of time that the drug remains in the circulation called ‘PEGylation’. This process involves adding chains of the polymer polyethylene glycol (PEG) to the enzyme. These PEG chains then protect the molecule from the human immune system and slow down the rate at which the kidneys remove them from the body. In other words, they can make the enzyme’s effects stronger and last for longer in the body. The researchers tested this super modified enzyme on mice and found that it fully protected them from a lethal dose of cocaine for at least three days.

The researchers have declared that, with further development, this enzyme could soon be used as an invaluable tool for the treatment of cocaine abuse. However, much more work still needs to be done in order to see whether the enzyme will act fast enough to prevent cocaine from exerting effects on a human user’s brain.