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MEDICINE | IN THE LAB

For smokers, a shot at quitting

A nicotine vaccine may break the cycle that fuels the habit.

July 17, 2006|Regina Nuzzo | Special to The Times

JOSEPH DARMIENTO of Coatesville, Penn., once quit smoking for 13 weeks, his longest cigarette-free stretch since he got hooked as a teenager. Inspiration arrived in the form of Marine Corps boot camp, where cigarettes were strict no-no's.

Now, though, the 37-year-old computer systems administrator just can't shake his pack-a-day habit.

After trying and failing with other tools such as the nicotine patch and gum, and Zyban pills, Darmiento has signed up to help test a new kind of quit-smoking tool: a nicotine vaccine.

The hope is that the vaccine could teach his immune system to recognize nicotine in his bloodstream and keep it from entering his brain. As smoking becomes less pleasurable and less reinforcing, it might be easier for him to combat his cravings. "Once I put the physical part behind me, then I can concentrate on the mental battle," Darmiento says.

The vaccine, called NicVAX, is far from proven technology. But it has shown promise in early trials even in smokers who had no plans to quit.

In March, the Food and Drug Administration granted NicVAX's manufacturer, Nabi Biopharmaceuticals of Boca Raton, Fla., a fast-track application to help speed the drug's review process.

Now nine centers across the U.S., including UCLA, are recruiting smokers for a Phase 2 clinical trial. Initial results of the trial, funded in part by a recent $4.1-million grant to Nabi from the National Institute on Drug Abuse at the National Institutes of Health, are expected in mid-2007.

Better quit-smoking therapies are sorely needed to treat today's smokers, who appear to smoke more heavily and be more addicted than in the past, says Elbert Glover, professor of public and community health at the University of Maryland and head of the Maryland trial. This year, more than 400,000 smokers in the U.S. will die from smoking-related illnesses, according to the Centers for Disease Control and Prevention. About 70% of the 49 million adults and 6 million teenagers who smoke in the U.S. say they would like to quit, and every year about 40% of them try.

Fewer than 3% succeed.

Scientists believe the new vaccine might help smokers such as Darmiento who haven't been able to quit with other methods.

On their own, nicotine molecules -- just like those in drugs such as heroin and cocaine -- are too small to trigger the body's immune system, says Dr. Victor Reus, professor of psychiatry at the UC San Francisco School of Medicine and head of the San Francisco trial. These molecules slip quickly and easily from the bloodstream into the brain, where they bind with nerve receptors and trigger a pleasurable dopamine release.

Thus, to create an effective vaccine, scientists attached nicotine molecules onto larger proteins. After injection with the vaccine, the immune system creates antibodies that specifically recognize nicotine. When a vaccinated smoker takes a drag, these antibodies attack nicotine in the bloodstream. Bound nicotine molecules, too big to cross the blood-brain barrier, are eventually eliminated harmlessly by the body.

Antibodies build up slowly, and patients get "six weeks of guilt-free smoking" after the first injection before they're instructed to quit, says Mitchell Nides, a consultant on the Los Angeles trial. "This is not a cold-turkey approach at all," he says.

Since the method targets nicotine, not the brain, researchers hope to see fewer side effects than with other pharmacological tools (see box). The antibodies could persist for months after injection, and possibly even longer with a booster shot, so the vaccine might also help guard ex-smokers against a relapse.

Using antibodies to treat drug abuse isn't new, Reus says. In the early 1970s, researchers tested monkeys with an experimental vaccine for heroin addiction. Today, new vaccines are being developed to treat addiction to heroin, cocaine, PCP and methamphetamine.

Other companies are also developing nicotine vaccines: Cytos Biotechnology of Zurich, Switzerland, which presented results of a Phase 2 clinical trial in Europe in May 2005; Xenova Group of Berkshire, England; and Prommune of Omaha, Neb.

An earlier, smaller test of NicVAX's safety included active smokers who had no plans to quit. Even so, results were surprisingly good, says Dorothy Hatsukami, professor of psychiatry at the University of Minnesota and lead author on the study's report. Thirty-eight percent of smokers in a group that received a higher dose of the vaccine quit smoking for at least a month, compared with 9% in the placebo group.

Still much remains to be studied. Researchers aren't certain if the vaccine is safe for pregnant women. And, for reasons that are still unclear, some smokers may not develop enough antibodies for the vaccine to be effective. With the new 300-patient clinical trial, scientists hope to determine what types of smokers are most likely to benefit from the vaccine.

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