Nicotine replacement therapy, such as pills, gum and patches, can make the road to quitting smoking a little less rocky, but these aren't always effective and a tremendous amount of discipline still plays the major role. A team of US-based researchers has now uncovered an enzyme found in nature they say could greatly improve on the effectiveness of smoking cessation aids, by devouring nicotine in smokers before it can deliver its "reward" to the brain.
Scientists at The Scripps Research Institute (TSRI) have toiled away for more than 30 years in an attempt to create an enzyme that can search for and destroy nicotine in the body, but without any great success. Now they have zeroed in on a natural enzyme derived from soil in a tobacco field. The enzyme is called NicA2 and comes from a bacteria known as Pseudomonas putida. As it turns out, it relies entirely on nicotine as a source of carbon and nitrogen.
The scientists put their new discovery to work in an experiment where serum from mice blood was combined with a hit of nicotine – a dose equivalent to that found in a single cigarette. Adding NicA2 to the mix saw the nicotine's half-life cut from somewhere between two and three hours to between nine and 15 minutes.
"The bacterium is like a little Pac-Man," said Janda. "It goes along and eats nicotine."
Following the promising performance, the researchers next sought to test out the enzyme's credentials as an actual drug candidate. This involved subjecting it to a temperature of 98° F (36.7° C) for three weeks and testing it for toxic metabolites that could occur as it eats up nicotine. The team reports the results of these experiments as encouraging, with the enzyme remaining stable and showing no signs of toxicity.
The researchers add that increasing the dosage of NicA2 and making some chemical modifications could reduce the nicotine's half-life even further.
"Hopefully we can improve its serum stability with our future studies so that a single injection may last up to a month," says Song Xue, a TSRI graduate student and first author of the study.
We have seen the development of vaccines designed to treat nicotine-addiction in the past, with a recent effort even led by Janda himself. But the promise shown by the NicA2 enzyme has the researchers particularly hopeful it could come to offer an alternative to current smoking cessation aids, which they claim fail in 80 to 90 percent of smokers.
"Our research is in the early phase of drug development process, but the study tells us the enzyme has the right properties to eventually become a successful therapeutic," says Janda.
The research was published in The Journal of the American Chemical Society.
Source: The Scripps Research Institute
