A MAGIC BULLET IN COCAINE WARS?

A "catalytic antibody" found to gobble up the drug in lab rats has
raised hopes. The trick is adapting it to humans.

Donald W. Landry took up the cocaine challenge at the height of the
crack epidemic, after hearing President Bush ask in a speech whether
science might be able to devise a vaccine that could render addictive
drugs harmless.

A decade later, Landry may have done just that.

Using methods seldom applied in drug-abuse research, he built a
"catalytic antibody" that eats cocaine in a lab rat's bloodstream the
way that Pac-Man gobbles bad guys in a computer maze.

This spring, MedImmune Inc., a Gaithersburg, Md., biotech company,
will join forces with Landry to refine his technique to make an
antibody strong enough to treat cocaine abuse in humans.

If Landry, a professor at the Columbia University medical college in
New York, has not found the "magic bullet" in the war on drugs, he
certainly appears to be as close as anyone.

"If he is successful," said Frank Vocci, director of treatment
research and development at the National Institute on Drug Abuse, "he
would actually have an antibody able to reduce cocaine to an inactive
substance as fast as people put it into their bodies."

Success is by no means assured. While Landry "has shown conceptually
that it can work," the antibody does not yet function rapidly or
efficiently enough to be used in humans, noted Scott Koenig,
MedImmune's senior vice president for research.

Koenig said MedImmune, by engineering and testing thousands of
variants of Landry's antibody as well as new candidates, expects to
show whether the technique can be commercially viable.

"We have no way of knowing," Koenig said. "But we'll have an answer in
2000."

Once proven, however, the treatment would still require years of
clinical evaluation before it could reach the market, he cautioned.

Nonetheless, the potential is enormous. The President's Office of
National Drug Control Policy, which has given Landry $2.8 million in
research grants since 1994, estimates that there are 5.2 million users
of cocaine and its derivatives in the United States and 3.3 million
addicts.

Americans spend an estimated $39 billion a year on cocaine, and the
drug's "social cost," in law enforcement, prisons, rehabilitation,
lost wages, medical care and family violence, is another $66 billion,
the drug-policy office estimates.

Landry's and MedImmune's goal is to create an antibody that will mop
up any cocaine in a person's bloodstream for about a month. Add
boosters, so that the person goes four or five months without a
reinforcing high, and the craving goes away. "And when that happens,
rates of abstinence go way up," Landry said, citing studies that he
said showed that heroin treatment with both methadone and counseling
produced abstinence rates of 60 percent to 80 percent, compared with
10 percent to 30 percent for programs relying on counseling alone.

Still, he cautioned, while the antibody effectively "vaccinates" a
person against cocaine for a month, it is not a "vaccine," which would
cause the body to become permanently immune.

Also, "a vaccine is different for something you want than for
something you don't want," said Alan I. Leshner, director of the
National Institute on Drug Abuse. "People want cocaine" and could
always wait for the vaccine to wear off.

And, said Landry, "everything we have accomplished so far is merely
proof of principle."

Indeed, Landry and MedImmune agree that his best-performing antibody
to date binds to individual molecules much too sluggishly and does not
change targets fast enough. And the antibody probably needs to be
"humanized," so that a body will not attack it by making an antibody
for the antibody.

MedImmune will try to do all this by testing many sample antibodies -
both Landry's and others made by MedImmune - and "tweaking" them to
enhance performance.

"I don't want to say it's a no-brainer," Koenig said. "It's
challenging, but we have the experience to give it a good shot. If it
can be done, we'll do it."