Enzyme to help smokers quit by eliminating nicotine in the blood before it reaches the brain
The World Heath Organization classifies smoking as a global epidemic and the single most preventable cause of death in the world, accounting for around five to six million deaths every year. Many researchers are hunting for new ways to help people shake this damaging addiction, from a vaccine that prevents the pleasurable effects of nicotine to magnetic pulses delivered to the brain that help dampen substance dependence.
A team at The Scripps Research Institute has been working on a novel technique for a number of years, attempting to engineer an enzyme that breaks nicotine down before it can reach the brain. The scientists revealed a major breakthrough back in 2015, initially discovering a natural enzyme called NicA2 in soil from a tobacco field that is produced by a bacteria known as Pseudomonas putida.
Since then, the team has been working to optimize the enzyme, making it more potent in hunting down and destroying nicotine in an animal's bloodstream and staying in the bloodstream longer. The newly developed enzyme is called NicA2-J1, and from the latest animal studies it is proving incredibly effective in reducing nicotine blood levels in rats.
A new article published in the journal Science Advances chronicles the most sophisticated animal testing of the enzyme to date. In rat models developed to mimic a human addiction to nicotine, the animals displayed incredibly low levels of nicotine in their bloodstream after being treated with the new enzyme. Even more importantly, the animals did not display significant signs of withdrawal after receiving the enzyme.
"What's unique about this enzyme is that it removes enough nicotine to reduce the level of dependence, but leaves enough to keep the animals from going into severe withdrawal," explains Olivier George, principle investigator on the project.
The study also examined the longer term effects of the enzyme, particularly in regards to relapse into addiction. Nicotine was withheld from the animals for 10 days, after which they were given an injection of nicotine to see if additive tendencies were reawakened. The animals originally treated with NicA2-J1 displayed significantly reduced addictive behavior compared to the untreated rats, suggesting the enzyme has long-term beneficial effects.
One of the intriguing aspects of this research is that the scientists are working to eliminate nicotine in the bloodstream before it reaches the brain. So unlike other new techniques being researched that often home in on the addictive brain mechanisms at play, this method stops the drug from getting to the brain in the first place.
"This is a very exciting approach because it can reduce nicotine dependence without inducing cravings and other severe withdrawal symptoms, and it works in the bloodstream, not the brain, so its side effects should be minimal," says George.
Needless to say these results have not been replicated in human subjects yet, but the researchers are confident that after years of work they are ready to move into human trials with the first enzyme effective at destroying nicotine while in the bloodstream. Safety and efficacy in humans are still major hurdles than need to be overcome but if the research continues to progress, this treatment may be an incredibly useful new smoking cessation aid that could save the lives of millions around the world.
The new research was published in the journal Science Advances.
Source: Scripps Research