An Addiction Vaccine, Tantalizingly Close

SAN DIEGO — Imagine a vaccine against smoking: People trying to quit would light up a cigarette and feel nothing. Or a vaccine against cocaine, one that would prevent addicts from enjoying the drug’s high.

Though neither is imminent, both are on the drawing board, as are vaccines to combat other addictions. While scientists have historically focused their vaccination efforts on diseases like polio, smallpox, and diphtheria — with great success — they are now at work on shots that could one day release people from the grip of substance abuse.

“We view this as an alternative or better way for some people,” said Dr. Kim D. Janda, a professor at the Scripps Research Institute who has made this his life’s work. “Just like with nicotine patches and the gum, all those things are just systems to get people off the drugs.”

Dr. Janda, a gruff-talking chemist, has been trying for more than 25 years to create such a vaccine. Like shots against disease, these vaccines would work by spurring the immune system to produce antibodies that would shut down the narcotic before it could take root in the body, or in the brain.

Unlike preventive vaccines — like the familiar ones for mumps, measles and so on — this type of injection would be administered after someone had already succumbed to an addictive drug. For instance, cocaine addicts who had been vaccinated with one of Dr. Janda’s formulations before they snorted cocaine reported feeling like they’d used “dirty coke,” he said. “They felt like they were wasting their money.”

It’s a novel use for vaccines that has placed Dr. Janda, who is 54, in the vanguard of addiction treatment. Because addiction is now thought to cause physical changes in the brain, doctors increasingly advocate medical solutions to America’s drug problem, leading to renewed interest in his work.

“It’s very fashionable now,” said Dr. Janda, seated in a black leather chair in his office. “When we started doing this 27 years ago, it wasn’t.”

In July, Dr. Janda’s lab — 25 researchers, most of graduate-school age — made headlines when it announced that it had produced a vaccine that blunted the effects of heroin in rats. Rodents given the vaccine didn’t experience the pain-deadening effects of heroin and stopped helping themselves to the drug, presumably because it ceased to have any effect.

But as has often been the case in Dr. Janda’s career, the breakthrough came on the heels of a setback: A Phase 2 clinical trial for a nicotine vaccine that was based largely on his work was declared a failure this summer when people receiving the drug quit smoking at the same rate as people receiving a placebo.

To this day, despite many promising breakthroughs, not one of Dr. Janda’s vaccines has won approval from the Food and Drug Administration. For despite many successes in the lab — including promising animal tests — the vaccines have yet to produce consistent results in humans during clinical trials.

“It’s like having the carrot right in front of the horse,” he said. “The big problem plaguing these vaccines right now is difficulty predicting in humans how well it’s going to work.”

Or, he added, “maybe I’m just unlucky.”

The scientific principle behind Dr. Janda’s vaccines is, as he put it, “simplistically stupid.” Much like vaccines against disease, they introduce a small amount of the foreign substance into the blood, causing the immune system to create antibodies that will attack that substance the next time it appears.

The difficulty is that molecules like cocaine, nicotine and methamphetamine are tiny — much smaller than disease molecules — so the immune system tends to ignore them. To overcome that, Dr. Janda attaches a hapten — which is either a bit of the drug itself, or a synthetic version of it — to a larger protein that acts as a platform. The last part of the vaccine is an adjuvant, a chemical cocktail that attracts the immune system’s notice, effectively tricking it into making antibodies against a substance it usually wouldn’t see.

“It’s not like some magical premise,” Dr. Janda said. “And the beauty of it is you’re not messing with brain chemistry.”

The contrast, he said, is to anti-opiates like Suboxone or methadone that are currently used to treat heroin addiction. Rather than blocking the drug’s effects, they seek to replace the heroin high.

Dr. Janda says he has tried and failed to make vaccines against alcohol and marijuana abuse. In the case of alcohol, he said, ethanol molecules proved just too small to attach to the protein that would deliver the immunity. And in the case of marijuana, the main ingredient that produces the high — tetrahydrocannabinol, or THC — hides too well inside the body.

He has also tried formulating a vaccine against obesity. Rather than block a foreign substance, that vaccine would block the effects of a peptide hormone produced by the stomach called ghrelin that signals hunger in the brain. So far, a version of the vaccine has been shown to lower food intake in animals, though — again — it’s unclear whether it will work in humans.

Even so, addicts and their families are clamoring to get into Dr. Janda’s clinical trials. He says he gets e-mails every week from addicts asking to be included. He has had to turn away parents who showed up at his office with their drug-addicted children after reading about his work.

“What am I supposed to do, go in the lab and pull it out of the refrigerator and inject you?” he said. “I guess it’s been so devastating in their families that they’re looking for anything, and there’s just nothing out there. It’s really sad when you see these types of things.”

Despite the disappointments, some scientists predict that Dr. Janda will succeed. No less an addiction expert than Dr. Nora Volkow, director of the National Institute on Drug Abuse, calls him a “visionary” who saw the opportunity to treat addiction with medicine decades before most. Indeed, one reason that her institute is a chief source of Dr. Janda’s financing is Dr. Volkow’s belief that his work will eventually produce a marketable vaccine.

“Now many people say, ‘Yes, of course’ ” to the idea of treating drugs through vaccines, Dr. Volkow said. “But that took many years, and he traveled the road when there was a lot of skepticism.”

Today, the scientists who are working to create vaccines against narcotics include Thomas Kosten at the Baylor College of Medicine and S. Michael Owens at the University of Arkansas. Dr. Kosten has had limited success with a cocaine vaccine, while Dr. Owens is focused on vaccines for methamphetamines.

All three researchers say they are hobbled by a lack of interest — read: financing — from pharmaceutical companies in vaccines for any drug other than nicotine, presumably because there is little money to be made in a shot given once every six months, and because such companies aren’t eager to associate their brands with drug addicts.

And yet Dr. Janda’s lifelong pursuit of vaccines against narcotics began not with some painful family struggle with addiction, but in a simple request in the 1980s from one of the Scripps Institute’s former corporate partners.

“They were interested in the whole antibody area,” he said. “They kind of approached me and said, ‘Could you make antibodies to a drug of abuse?’ So we embarked on this.”

Dr. Janda spent many years trying to bring his own vaccines to market. In the ’80s and ’90s, he helped start some small pharmaceutical companies that patented and tested his work, with varying degrees of success. One burned through $60 million of venture capital with nothing to show for it; another sold for $95 million in 1999, but “due to bad management and bad splits, I ended up with about enough money for a case of beer,” he said — even more disappointing, perhaps, for a man with a taste for expensive bourbon.

These days, Dr. Janda prefers to publish his results in scientific journals and let others try to bring the vaccines to market.

He is quick to caution that taking away someone’s ability to get high off of one drug hardly cures them of their addiction problems. There’s nothing to stop a vaccinated cocaine addict, for example, from turning to methamphetamines.

Like any anti-addiction treatment, his vaccines are simply meant as “a crutch for people wanting to go into abstinence,” Dr. Janda said. “The whole thing with addicts is you have to want to get off the drug, or it’s not going to happen.”

He is also wary of ethical issues posed by his work. Today, a recovering cocaine addict will pass a drug test just days after getting clean. But once vaccinated, that person could be tested for antibodies for up to six months, alerting employers to his struggles with addiction.

“Before a parent takes a kid into college, can she take him in for a round of vaccines against all drugs?” asked Jenny Treweek, a researcher at Janda Laboratories who is working on a vaccine for Rohypnol, otherwise known as the date-rape drug. “Some teenagers might have a real problem with that.”

It’s questions like that — and the desire to solve the molecular puzzle he’s set up for himself — that motivate Dr. Janda to spend seven days a week in his lab, he said. He spends much of that time tweaking the components of his vaccines — trying different proteins or haptens, adjusting the adjuvants — hoping to hit precisely the right formula.

“If I vaccinated three people and they all got the same” immune response, he said, “then you would have a really straightforward shot how to move things forward.”

But with nearly 30 years of tweaking already under his belt, he seems increasingly resigned to the idea that it might not be him who eventually moves it across the finish line.

“I figure I have eight or 10 years left,” he said. “If something doesn’t go in eight or 10 more years, then it’s someone else’s turn.”

Read more…

This entry was posted in Uncategorized. Bookmark the permalink.