четверг, 19 июня 2008 г.

Are Vaccines the Answer to Addiction?

A vaccine that would teach the immune system to attack and destroy cocaine before the drug reached the brain is poised to enter its first large-scale clinical trial in humans. The shot is still years away from FDA approval, but the underlying concept--inoculating those at risk of addiction--is attracting increased interest.

Besides cocaine, researchers are developing vaccines against such highly addictive substances as nicotine, heroin and methamphetamine. NicVax, a nicotine vaccine by Nabi Biopharmaceuticals, is the furthest along in development. In November, one year into a phase-two clinical trial, the company reported that twice as many people taking the vaccine had quit smoking as those taking a placebo.

Addiction vaccines work the same way as the traditional vaccines used to treat infectious diseases such as measles and meningitis. Basically, they marshal the body's defense system. But instead of targeting bacteria and viruses, these new vaccines zero in on addictive chemicals that people snort, shoot or swallow.

If the new treatments make it to market, experts hope they will overcome one big hurdle that existing anti-addiction medications have failed to clear--widespread resistance to the idea of treating addicts with drugs. "Vaccines are nowhere near as stigmatized as giving drug therapy to the addicted," says Baylor College of Medicine psychiatrist Thomas Kosten, who is leading research on the cocaine vaccine. " 'Vaccine' sounds more wholesome than 'drug'."

Despite a growing body of evidence that addiction, like so many other diseases, is rooted in a person's genes, it is often seen as a personal weakness, not a medical condition to be treated or cured. That impression, some experts say, has stymied research into potential treatments for the estimated 20 million Americans who struggle with alcohol and drug addiction. "It's easy to interest the scientists, but not so easy to interest the marketing people," says Kosten.

Each of the proposed vaccines employs a similar biochemical strategy. Because the addictive-drug molecules are small enough to evade the body's immune system, they can slip undetected from the lungs and bloodstream into the central nervous system, where they disrupt brain chemistry and turn on addiction pathways that can be difficult to shut off. But when attached to a larger molecule, the addictive substances can't hide. To make the cocaine vaccine, Kosten attached the cocaine molecule to a protein made by cholera-causing bacteria. When injected, the vaccine triggers the immune system to develop antibodies. The next time the drug is ingested, the thinking goes, these antibodies will latch onto it and prevent it from crossing the blood-brain barrier.

Current anti-addiction medications do not prevent addictive drugs from entering the brain. Instead, these treatments block the drugs' neural targets, so that when a drug reaches the brain it has no place to go. Such medications --known as small-molecule therapies--have met with only limited success so far. For example, methadone, a medication used to treat heroin addicts, has itself been associated with addiction and overdose, because in addition to blocking heroin's entrance to brain cells, methadone also mimics the narcotic, producing its own, milder high. Drugs that treat alcohol and nicotine addiction have been effective only in small subsets of patients and have produced severe side effects in some cases. "With these types of drugs, the brain's receptors are still being manipulated, albeit by a replacement drug," explains Nora Volkow, director of the National Institute on Drug Abuse, which funds research on the addiction vaccines. In theory, she says, the vaccines would circumvent some of these problems by neutralizing the addictive substance before it reached the nervous system.

One day, anti-addiction vaccines could be used to prevent substance abuse as well as treat it. "It would be great if we could give kids a vaccine that would make them impervious to the effects of hard drugs," says Volkow. "In reality, we are still many years away from that."

For the cocaine vaccine to succeed, researchers will have to solve several technical problems. In early studies, for example, not all of the subjects developed antibodies against the cocaine-cholera molecule, and some developed much stronger responses than others. "This is not like an antibiotic, which is directed against the invading microbe and has roughly the same effect on everyone," says Volkow. "Here, we are stimulating the immune system, which can react differently depending on the individual."

Another concern is that a serious drug user could overwhelm the immune response by simply ingesting more cocaine than the immune system could handle. He could also switch to another drug, which the vaccine would be powerless to protect against. The determination and desperation of drug addicts notwithstanding, however, vaccines have an extraordinary track record. They could prove to be the solution to one of our most enduring public-health problems.

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