Scientists have designed an enzyme that destroys nicotine in the bloodstream before it reaches the brain, according to a report published in the journal Science Sciences.
In tests on laboratory rats, treatment quickly reduced the motivation of animals to take nicotine, reversing the signs of nicotine dependence, and kept them from relapse when they were given access to nicotine again.
The study's principal investigator, Olivier George, said: "This is a very exciting approach because it can reduce nicotine dependence without causing cravings and other serious withdrawal symptoms and functioning in the bloodstream rather than in the brain."
Nicotine dependence is what prevents smoking of smoked tobacco, despite all the harm it brings to their health. Researchers estimate that about 60 percent of people experiencing cigarettes end up as smokers every day and about 75 percent of everyday smokers come back after abandonment.
Reversing nicotine dependence by blocking nicotine in cigarette smoke to reach the brain has long been a promising strategy. However, previous efforts have not yielded drugs that reduce nicotine levels in blood enough to be effective.
The enzyme tested in this study, NicA2-J1, is a version of a natural enzyme produced by the bacterium Pseudomonas putida. It was modified to optimize its strength, its residence time in the blood and other pharmacological properties.
During a series of experiments, laboratory rats spent 21 hours each day, for 12 days, in a chamber where they could push a lever to give themselves intravenous nicotine infusion. In this way they learned to self-manage nicotine, and became dependent on it. After twelve days, access to nicotine was given only every 48 hours, which led them to experience withdrawal symptoms between periods of access and escalation of their intake.
The animals receiving the highest dose of NicA2-J1 (10 mg / kg) continued to self-administer nicotine when they could, but showed very low levels in the blood of the molecule as compared to controls that did not receive the enzyme. Nicotine withdrawal signs, such as pain sensitivity and aggressive behaviors, decreased respectively during periods of non-access, as compared to untreated controls.
With such promising results in preclinical trials, researchers are now hoping to get NicA2-J1 in clinical trials in humans.