Pubdate: Tue, 03 May 2011
Source: Weekly Journal, The (CN ON)
Copyright: 2011 Transcontinental Media
Contact:  http://www.eastottawa.ca/
Details: http://www.mapinc.org/media/3567
Author: Mark Long

QUEST FOR VACCINES TO TREAT ADDICTION

Frustrated by the high relapse rate of traditional addiction
treatments, scientists are working on a strategy that recruits the
body's own defenses to help addicts kick drug habits.

The new approach uses injected vaccines to block some addictive
substances from reaching the brain. If a vaccinated addict on the path
to recovery slips and indulges in a drug, such as tobacco or cocaine,
no pleasure will result.

"You still have to mentally say to yourself, 'I'm not going to do
this,' but it's so much easier to say it when you know if you light a
cigarette, you're not going to get any pleasure out of it," says
Stephen Ballou, a 56-year-old banker who got a nicotine vaccine in a
2007 clinical trial to help kick his pack-a-day habit. He says he
hasn't smoked since.

Some medications currently available to treat addictions typically
work by mimicking a drug in the brain. For example, methadone stands
in for heroin and the nicotine patch for cigarettes. Other medications
block activity in the brain's reward system. Alkermes Inc.'s
once-monthly Vivitrol injection does this for alcoholics and opioid
addicts, while Pfizer Inc.'s Chantix pills block the brain's pleasure
receptors activated when people smoke.

Small-molecule drugs like Chantix that function inside the brain can
raise safety concerns. Chantix carries a federally mandated warning to
users of possible depression and suicidal thoughts. A spokesman for
Pfizer notes that no causal link between Chantix and such symptoms has
been made.

By contrast, addiction-treatment vaccines work in the bloodstream, not
the brain. Clinical trials have so far revealed no significant side
effects, though the vaccines would do nothing to combat cravings. They
work by tricking the body to reject drugs as if they are foreign
pathogens. Normally, tiny drug molecules wend their way through the
bloodstream to the brain, unleashing a flood of chemicals involved
with pleasure and gratification. The drug molecules are too small to
goad the immune system into generating antibodies to fight them off.

Scientists have figured out how to attach molecules similar to
addictive drugs to much bigger antigens, such as deactivated versions
of cholera or the common cold. When injected, these so-called
conjugate vaccines spur the immune system to create antibodies to
fight the tiny, addictive-drug molecules. These antibodies have in
several studies glommed on to molecules of nicotine, cocaine and
heroin ingested by lab animals and in some cases people, blocking them
from triggering the pleasure centers in the brain.

Some medications currently available to treat addictions typically
work by mimicking a drug in the brain. For example, methadone stands
in for heroin and the nicotine patch for cigarettes. Other medications
block activity in the brain's reward system. Alkermes Inc.'s
once-monthly Vivitrol injection does this for alcoholics and opioid
addicts, while Pfizer Inc.'s Chantix pills block the brain's pleasure
receptors activated when people smoke.

Small-molecule drugs like Chantix that function inside the brain can
raise safety concerns. Chantix carries a federally mandated warning to
users of possible depression and suicidal thoughts. A spokesman for
Pfizer notes that no causal link between Chantix and such symptoms has
been made.

By contrast, addiction-treatment vaccines work in the bloodstream, not
the brain. Clinical trials have so far revealed no significant side
effects, though the vaccines would do nothing to combat cravings. They
work by tricking the body to reject drugs as if they are foreign
pathogens. Normally, tiny drug molecules wend their way through the
bloodstream to the brain, unleashing a flood of chemicals involved
with pleasure and gratification. The drug molecules are too small to
goad the immune system into generating antibodies to fight them off.

Scientists have figured out how to attach molecules similar to
addictive drugs to much bigger antigens, such as deactivated versions
of cholera or the common cold. When injected, these so-called
conjugate vaccines spur the immune system to create antibodies to
fight the tiny, addictive-drug molecules. These antibodies have in
several studies glommed on to molecules of nicotine, cocaine and
heroin ingested by lab animals and in some cases people, blocking them
from triggering the pleasure centers in the brain.

A vaccine isn't viable for treating alcoholism-among the costliest of
addictions-because alcohol molecules are far too small to trigger the
immune system, says Thomas Kosten, a pioneer of addiction-vaccine
research at Baylor University in Houston.

Most commercial vaccine-development efforts are focused on tobacco.
Slightly more than a fifth of U.S. adults light up regularly.

Nearly half of U.S. smokers try to quit each year, but just 4% to 7%
of quit attempts-most of them unaided-are successful long-term,
according to American Lung Association estimates.

Just one out of three people trying to quit-at best-ends up kicking
the habit for good, even with cessation aids, says Norman Edelman, the
Association's chief medical officer and a professor of medicine at New
York's Stony Brook University.

Nabi Biopharmaceuticals, a Rockville, Md., biotechnology company, is
farthest down the path toward possible regulatory approval for an
addiction vaccine, with two Phase III trials underway in several U.S.
sites of its NicVAX product to help people quit smoking.

"The relapse is the biggest thing," says Raafat Fahim, the company's
chief executive. "With antibodies staying a long period of time with
you, it then protects you against the relapses."

Nabi in 2009 got a $10 million grant from NIDA, and sealed a licensing
pact with the U.K.'s GlaxoSmithKline PLC that, including a $40 million
up-front payment, could be worth up to $500 million, plus possible
royalty payments.

Nabi's Phase II trial-the one Mr. Ballou participated in-found that
smokers taking NicVAX were about three times as likely to be off
cigarettes 44 weeks after vaccination than subjects given a placebo,
Dr. Fahim says. That test was very small, and the results weren't as
good as Pfizer got from a much larger Phase III trial of Chantix, he
says. Subjects in Nabi's Phase III trial will get an extra dosage of
NicVax compared to those in the Phase II trial.

One of the possible advantages of a vaccine, which would likely be
used alongside psychological therapy and possibly other medications,
is that it could require a once-a-month injection, as opposed to
current anti-addiction medications that sometimes need to be taken
several times a day.

"It's a lot easier to take a couple of vaccinations than to put on a
patch every day, or keep chewing that nicotine gum, or doing whatever
measures you're taking," says Phil Skolnick, director of the division
of pharmacotherapies and medical consequences of drug abuse at NIDA.

Recent results from a test of an anticocaine vaccine in mice at Weill
Cornell Medical College in New York were encouraging, researchers say.

"We give intravenous dosages of cocaine that's in excess of what
humans take and it's like water to the mice" that have received the
vaccine, says Ronald Crystal, the study's lead investigator and the
chairman of genetic medicine at Weill Cornell. "They don't run around
and get hyperactive." The researchers are now studying the vaccine in
non-human primates.

Meanwhile, Dr. Kosten continues work on the TA-CD cocaine vaccine with
a 300-subject, randomized, multi-site trial. Dr. Kosten says he hopes
to report on the outcome of this trial sometime next year.
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