Gene therapy against nicotine may help smokers quit

An experimental vaccine against nicotine, delivered using gene therapy, prevents the substance from reaching the brain and may make quitting easier for smokers, a study using mice indicates.

A single dose of vaccine allowed the liver to produce antibodies that stopped most of the nicotine from getting to the brain, according to a study in the journal Science Translational Medicine. The concentration of nicotine in the brains of treated mice was just 15 percent of that in untreated ones.

Of the more than 4,000 chemicals in cigarette smoke, it is nicotine that leads to addiction, the researchers wrote. Keeping the substance away from the brain might stymie nicotine’s addictive power by preventing smokers from enjoying their cigarettes, giving them no incentive to relapse, said Ronald Crystal, one of the study’s researchers.

“This looks really terrific if you’re a mouse, but the caveat is that they aren’t small humans,” said Crystal, the chairman of genetic medicine at Weill Cornell Medical College in New York, in a telephone interview.

The gene therapy delivers the vaccine to the liver using a virus engineered not to be harmful. The gene sequence for the antibodies is inserted into liver cells, which then begin to create antibodies to nicotine.

“The antibody is floating around like Pac-Man in the blood,” Crystal said. “If you give the nicotine and the anti- nicotine gobbles it up, it doesn’t reach the brain.”

The idea of vaccines against nicotine has emerged before, in the form of injections used to trigger an immune response. Those methods proved ineffective, according to the researchers. They turned to gene therapy to trigger production of antibodies.

About 20 percent of U.S. adults are smokers, and most relapse shortly after quitting.

“We don’t have very effective therapies,” Crystal said. “The problem is even with the drugs we have now, 70 percent of people go back to smoking within 6 months of trying to quit.”

The virus vector has been previously given to children with a different disease and appears to be safe, he said.

His group plans to continue studying the vaccine in rats and nonhuman primates, and has talked to pharmaceutical companies about testing, he said. The gene-therapy vaccine method may work in other addictions as well, Crystal said.