An enzyme in a nicotine-eating bacteria that can be recreated in the lab may be useful as a drug candidate to help people quit smoking, researchers have shown. The research, from scientists at The Scripps Research Institute (TSRI) shows that this enzyme offers a possible alternative to current smoking cessation aids, which are shown to fail in at least 80 to 90 percent of smokers.
Kim Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI, said:
“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."
The concept behind an enzyme therapy? Search and destroy nicotine before it reaches the brain, depriving a person of the “reward” of nicotine that can trigger relapse into smoking.
Janda and his colleagues have struggled for more than 30 years to create such an enzyme in the lab, but they recently ran across a potential enzyme found in nature, NicA2 from the bacteria known as Pseudomonas putida. It turns out this bacterium, originally isolated from soil in a tobacco field, consumes nicotine as its sole source of carbon and nitrogen.
Researchers characterized the bacterial enzyme responsible for nicotine degradation and tested its potential usefulness as a therapeutic.
The researchers first combined blood serum from mice with a dose of nicotine equivalent to one cigarette. When they added the enzyme, the nicotine’s half-life dropped from two to three hours to just 9 to 15 minutes.
Janda said a higher dose of the enzyme, could, with a few chemical modifications, reduce the half-life of nicotine even further and prevent it from ever reaching the brain.
As far as its practicality as a drug candidate, the enzyme stayed stable in the lab for more than three weeks at 98 degrees Fahrenheit, which Janda said was pretty remarkable. Importantly, the researchers detected no toxic metabolites produced when the enzyme degraded nicotine.
First author Song Xue said:
“The enzyme is also relatively stable in serum, which is important for a therapeutic candidate. Hopefully we can improve its serum stability with our future studies so that a single injection may last up to a month."
Song Xue, Joel E. Schlosburg, Kim D. Janda. A New Strategy for Smoking Cessation: Characterization of a Bacterial Enzyme for the Degradation of Nicotine. Journal of the American Chemical Society, 2015; 150806132815001 DOI: 10.1021/jacs.5b06605
Photo: CDC/ Janice Haney Carr