HOUSTON SCIENTISTS SEE HOPE IN COCAINE VACCINE

Baylor Doctors Say Shots Block the Drug's High

The needle may be one of addiction's enduring symbols, but two
Houston researchers hope injections of modified cocaine actually
provide the first-ever medication for people hooked on the destructive drug.

The Baylor College of Medicine scientists have developed a cocaine
vaccine, currently in clinical trials, that stimulates the immune
system to attack the real thing when it's taken.

As a result, cocaine no longer provides a kick.

"For people who have a desire to stop using, the vaccine should be
very useful," said Dr. Tom Kosten, a psychiatry professor who was
assisted in the research by his wife, Therese, a psychologist and
neuroscientist. "At some point, most users will give in to temptation
and relapse, but those for whom the vaccine is effective won't get
high and will lose interest."

Kosten, who joined Baylor 18 months ago, asked the Food and Drug
Administration in December to green-light a multi-institutional trial
to begin in the spring. It presumably would be the final clinical
hurdle before the vaccine might be approved for treatment.

Approval would mark a breakthrough in the treatment of cocaine
addiction, which now mostly involves psychiatric counseling and
12-step programs. Over the years, Kosten notes, more than 50
pharmaceutical options have been investigated and found wanting.

The vaccine also could raise interesting ethical questions involving
who should get inoculated and what happens if confidential
information about those receiving it becomes known. Although
developed for therapeutic purposes - the number of cocaine addicts in
this country is estimated at more than 2 million - the vaccine
eventually is expected to be used for prevention, as well.

The questions include whether parents would be allowed to have their
children inoculated; whether it would amount to coercion to make it a
condition for lighter criminal sentences; whether employers might
happen upon such information and use it discriminatorily; and whether
to use it on pregnant addicts to protect the fetuses.

The questions don't just reverberate about this vaccine: Tom Kosten
also is at work on vaccines for methamphetamine, heroin and nicotine.
Two other nicotine vaccines are being investigated by other scientists.

"Anti-drug vaccines may provide an important weapon against
addiction," said Frank Vocci, director of treatment research and
development at the National Institute of Drug Abuse, which funded
much of the research. "We're starting to see progress. We just need
to see more."

Concept Called 'Clever Idea'

No one denies the extent of the problem. Federal estimates put the
number of Americans classified with substance abuse or dependence at
22.2 million and the cost to the country at $484 billion a year -
almost three times the cost of cancer.

The Kostens' cocaine vaccine has been more than a decade in the making.

In concept, the idea seems simple. Cocaine (and many other drug)
molecules are so small the immune system fails to recognize them and
make the antibodies necessary to mount an attack. To help the immune
system, Kosten attached inactivated cocaine to the outside of
inactivated cholera proteins.

In response, the immune system not only makes antibodies to the
combination, which is harmless, but also recognizes the potent naked
drug when it's ingested. The antibodies bind to the cocaine and
prevent it from reaching the brain, where it normally would generate
the highs that are so addictive.

"It's a very clever idea," says David Eagleman, a Baylor
neuroscientist. "Scientists have spent the last few decades figuring
out reward pathways in the brain and how drugs like cocaine hijack
the system. It turns out those pathways are difficult to rewire once
they've seen the drug. But the vaccine just circumvents all that."

Kosten says the idea goes back to the 1950s, when scientists devised
a vaccine to treat potentially fatal overdoses of the then-popular
heart medication digitalis, and the 1970s, when researchers
experimented with a heroin vaccine before abandoning it.

Kosten took up the idea in the mid-1990s, figuring cocaine was a
better candidate because the enzyme for breaking it down is in the
bloodstream, not the liver, like most drugs. While they were at Yale,
he led the clinical trials and his wife conducted the animal experiments.

The most impressive result involved a study at Columbia University in
New York, where users who had no interest in being treated were paid
to be vaccinated. Those who got a low dose saw little change. Those
who got a high dose reduced their drug use by more than 50 percent.
In Kosten's words, "it didn't do what it used to do."

But one expert warns against expecting too much.

"Addiction vaccines are a promising advance, but it's unlikely any
treatment in this field will work for everyone," said Dr. David
Gorelick, a senior investigator at the National Institute on Drug
Abuse. "Still, if they prove successful, they will give those working
in drug addiction an important option."

To be sure, the vaccine is still a work in progress.

There also are questions about dedicated users' ability to overcome
the vaccine if they ingest more cocaine than the immune system can
fight off, and whether they'll simply switch drugs once they stop
getting a high from cocaine.

FDA May Act in a Few Years

Kosten acknowledges those are concerns. But he also notes that most
users would have a hard time affording the amount of cocaine
necessary to override the immune response, and that study
participants didn't switch drugs when the cocaine lost its effect.
Vaccines also could be combined - as is done with mumps, measles and
rubella - if the concept pans out.

Vaccines' ethical concerns have occasioned academic papers, committee
investigations and conferences. In a 2004 report, the National
Academy of Sciences' Center for Studies of Behavior and Development
lauded the new method's promise, but cautioned that it "poses
distinct behavioral, ethical, legal and social challenges that
require careful scrutiny."

"There are certainly important issues there, but I don't think any
are insurmountable," said Dr. Peter Cohen, a Georgetown law professor
and chairman of the District of Columbia Medical Society's physician
health committee. "Overall, the benefits to society of such vaccines
would outweigh the risks."

Addicts also will benefit from other treatment at the same time, such
as behavioral therapies or counseling, says Kosten. Emphasizing that
there was a reason drugs were used in the first place, he says the
vaccine is not meant as "a stand-alone treatment."

Still, FDA approval could come within a few years, Kosten speculates,
if he gets the go-ahead to conduct the Phase III trial next year and
it succeeds. The trial would enroll about 300 patients at six sites
around the country, one in Houston.

So, what will it mean to Kosten if and when that approval comes down?

"It'll be great," he said. "It'll also mean a new opportunity to make
more vaccines and move on to more addiction problems."