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Nicotine Destroying Drug Candidate Discovered

Lighting a cigarette

(Pakura, Pixabay)

7 August 2015. Biochemists at Scripps Research Institute reported on an enzyme derived from naturally-occurring bacteria that shows in lab tests can remove nicotine in the blood, with potential as a drug to help smokers quit. The team from the lab of chemistry professor Kim Janda at Scripps’s La Jolla, California campus described their findings earlier this week in Journal of the American Chemical Society (paid subscription required).

Janda’s group investigates catalytic enzymes, including those with potential for treating nicotine addiction. In their study Janda and colleagues studied NicA2, an enzyme derived from Pseudomonas putida, bacteria found in soil and fresh water that digest and break down organic matter as part of the carbon cycle. This property also gives the microbes an ability to break down organic toxins, which at one time attracted the attention of conservationists as a method for cleaning up toxic wastes.

Cigarette smoking continues to involve large numbers of people in the U.S., with 42 million adults currently using tobacco. Centers for Disease Control and Prevention says the percentage of Americans smoking cigarettes declined from 21 percent in 2005 to 18 percent in 2013, but smoking is still the leading cause of preventable disease and death in the U.S., causing more than 480,000 deaths a year. Also, some 16 million Americans are living with a smoking-related disease. Despite sophisticated behavioral techniques and chemical aids, getting smokers to quit is difficult, with multiple relapses common among people trying to stop smoking.

The Scripps team tested the enzyme NicA2, derived from Pseudomonas putida, as a way to break down and destroy nicotine in the bloodstream before it reaches the brains of people who smoke, thus blocking its addictive mechanism and helping people break the habit. In the lab, researchers mixed the equivalent amount of nicotine found in a cigarette with blood serum from a mouse, then added NicA2. They found that before adding NicA2, nicotine has an active lifetime of 4 to 6 hours, but after adding the enzyme, the nicotine lasts only 18 to 30 minutes.

The researchers then looked into other properties of NicA2 as a potential drug candidate. They discovered the enzyme remains stable for more than 3 weeks at a temperature of 98 degrees F. In addition, the team found degraded nicotine does not generate toxic byproducts from its reaction to NicA2.

Despite these findings, an important issue remains, namely the bacterial components of the enzyme, which could trigger an immune reaction in humans and would need to be neutralized. Nonetheless, the researchers believe they identified a treatment candidate with a favorable biochemical profile that could open up a new strategy for smoking cessation.

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