By Danielle Pritchett

A UK professor recently announced a breakthrough that could possibly prevent irreversible damage caused by a cocaine overdose.

Chang-Guo Zhan, a professor in the department of pharmaceutical sciences, led a research project to modify an enzyme that would break down cocaine before it causes irreparable harm.

The body already has an enzyme that uses water to naturally break down cocaine into two inactive compounds, Zhan said. However, the enzyme works slowly, taking around 90 minutes to break down half of a tiny amount of cocaine, he said, and it takes much longer to break down the amount in an overdose.

Zhan’s work focused on changing the enzyme’s structure to make it work more quickly.

The modified enzyme has a much higher activity level, working 2,000 times faster than the natural molecule and needing only seconds to break down the cocaine. The enzyme is administered through injection and is not harmful, Zhan said, due to its origin as a natural element of the body.

It has taken years of research for Zhan and his team to get to this point.

“We started this research officially in 2003,” Zhan said. “That was the first year that I moved from Columbia University to the University of Kentucky College of Pharmacy. That was the first year that we had (National Institute of Health) support for this project.”

Graduate student Wen Chao Yang worked as a research assistant on the project for three years. Yang said there is a pressing need for anti-cocaine medication because the drug has such dangerous effects.

“Cocaine is recognized as the most reinforcing of all drugs of abuse,” Yang said. “There is no anti-cocaine medication available. The disastrous medical and social consequences of cocaine abuse have the made the development of an anti-cocaine medication a high priority.”

The team first used computer modeling to understand the mechanism of the enzyme that breaks down cocaine.

“The first thing we wanted to know was how the cocaine binds with the enzyme and how the cocaine is converted into biologically inactive metabolites,” Zhan said.

They then modified the natural enzyme and sent samples to a collaborator at the University of Michigan medical school. Animal testing was conducted with very small amounts of enzyme that would not be harmful, Zhan said.

Research remains ongoing and the project will need to team up with a company for investment, Zhan said. The team hopes to eventually obtain the approval of the Food and Drug Administration so the enzyme can be made available for widespread use.

“We are very confident that we can gain FDA approval, but we have a lot of work to do,” Zhan said.

The team must produce and purify the modified enzyme in large scale and conduct further animal testing based on FDA standards. After sending that data in, the FDA has to approve testing on human volunteers, which is carried out in three phases. Only after successful trials can the team submit their data for final approval.

The team led by Zhan is not the only one to try the enzyme approach, he said, though no other modified enzyme has been as efficient. Yang said if the enzyme is successful in further testing, it could be a revolutionary drug.

“At present, doctors can only try to relieve the symptoms of cocaine overdose and cannot really solve the overdose problem. If this enzyme works well in humans, it would be a powerful therapy to remove drugsfrom a user’s body,” Yang said.

Cocaine is one of the most addictive drugs, and one that directly affects the brain, according to the National Institute on Drug Abuse. A tolerance for the drug usually develops, resulting in a constant increase in the amount used. This increase is often the reason for overdose.

Zhan said the approach of neutralizing cocaine in the body has led many to wonder if it might be effective against other drugs. The idea could work theoretically, he said, though the entire process would have to be restarted focusing on a different enzyme.

“It does depend on the specific situation,” Zhan said. “To use the general enzyme approach, we would have to identify a type of enzyme that does the desirable work which we can improve.”