TSRI researchers say enzyme may work as an antismoking treatment

Recent work by scientists at The Scripps Research Institute (TSRI) has spotlighted a bacterial enzyme and its potential as a drug candidate to alleviate an addiction to tobacco.

Medications to help smokers quit smoking that are currently on the market fail to effectively suppress tobacco addiction--with as much as 80% to 90% thought to be ineffective. Nicotine is a substance responsible for the addictive nature of tobacco smoke, and this new enzyme, which was isolated from the bacteria Pseudomonas putida, targets nicotine and degrades it before it reaches the brain.

Since nicotine works by triggering the reward pathway in the brain--a central reason for smokers to relapse--removing nicotine may lower this rate of relapse. "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," says Kim Janda, the principal investigator of the study, which was published in the Journal of the American Chemical Society.

Kim Janda

Janda and his team have been attempting to develop a nicotine-degrading enzyme for more than 30 years. The new enzyme, NicA2, was harvested from a bacteria found in the soil of a tobacco field.

They observed the enzyme's potential initially by combining blood serum from a mouse and a dose of nicotine representative of smoking one cigarette. They saw the half-life of nicotine drop from 2 to 3 hours to a mere 9 to 15 minutes after adding the enzyme. After metabolite studies they concluded there were no detectable toxic byproducts. More convincingly was the stability of the enzyme, which withstood 98 degrees Fahrenheit while retaining its structure in serum.

"The enzyme is also relatively stable in serum, which is important for a therapeutic candidate," said Song Xue, a graduate student in the lab and the first author of the study.

The next step for the team will be to alter the enzyme's bacterial makeup in order to optimize its interaction with the host's immune system once administered into the blood.

"Hopefully we can improve its serum stability with our future studies so that a single injection may last up to a month," Xue added.

- here's the release
- read the research abstract

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