Researchers have been exploring a bacterial enzyme that could potentially be used as a drug treatment to help people quit smoking.
The idea behind this enzyme therapy would be to seek out and destroy nicotine before it reaches the brain — depriving a person of the “reward” of nicotine that can trigger relapse into smoking.
“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,” said Dr. Kim Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at The Scripps Research Institute (TSRI).
The new study, published in the Journal of the American Chemical Society, offers a possible alternative to current smoking cessation aids, which are shown to fail in at least 80 to 90 percent of smokers.
For more than 30 years, Janda and his colleagues have struggled to create such an enzyme in the lab, but they recently stumbled upon a potential enzyme found in nature — NicA2 from the bacteria known as Pseudomonas putida. This bacterium, originally isolated from soil in a tobacco field — consumes nicotine as its sole source of carbon and nitrogen.
“The bacterium is like a little Pac-Man,” said Janda. “It goes along and eats nicotine.”
The researchers began testing the enzyme’s potential usefulness as a therapeutic.The researchers first combined serum (a component of blood) 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 — with a few chemical modifications — could reduce the half-life of nicotine even further and keep it from ever reaching the brain.
The researchers then subjected the enzyme to a battery of tests to determine its practicality as a drug candidate. “It was a long shot,” said Janda. “If it didn’t have the right metrics, it would be a bust.”
The results have been promising. The enzyme stayed stable in the lab for more than three weeks at 98 degrees Fahrenheit — which Janda admitted was “pretty remarkable.” Importantly, the researchers detected no toxic metabolites produced when the enzyme consumed nicotine.
“The enzyme is also relatively stable in serum, which is important for a therapeutic candidate,” said Song Xue, a TSRI graduate student and first author of the new study.
The next step is to alter the enzyme’s bacterial makeup, says Janda, which will help mitigate potential immune liabilities and increase its therapeutic potential.
“Hopefully we can improve its serum stability with our future studies so that a single injection may last up to a month,” added Xue.
Source: The Scripps Research Institute