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Scripps Research Institute Scientists Develop Antidote for Cocaine Overdose
Date:4/18/2012

ty for an antidote is a "passive" cocaine vaccine, a ready-made solution of antibodies much like those used to treat snakebite. As Janda and his colleagues have shown in previous research, injected drug-specific antibodies can swiftly remove drug molecules from the bloodstream. This immediately reduces a drug's direct effects on the heart and nearby organs, but it also pulls the drug from the organ where it does the most damage—the brain. If the drug molecules are small enough to cross the blood-brain barrier, the sudden lowering of their bloodstream concentration causes them to diffuse rapidly out of brain tissue.

Cocaine molecules are small enough to diffuse this way, and in 2005 Janda and his lab reported that injections of a mouse-derived anti-cocaine antibody, GNC92H2, could keep mice alive despite cocaine doses that killed unprotected mice. Mouse antibodies are not ideal for use in humans, though; they are "foreign" enough that human immune systems eventually develop a reaction against them.

Promising New Results

In the new study, Janda and Jennifer B. Treweek, PhD, a research associate in Janda's laboratory, used a genetically engineered mouse that can produce fully human antibodies against cocaine molecules. The best of these antibodies, GNCgzk, showed ten times the cocaine-binding affinity of GNC92H2, the molecule in the 2005 study.

In a preliminary test, the scientists showed an injection of GNCgzk antibodies 30 minutes before an injection of a lethal cocaine dose greatly reduced the signs of overdose—such as awkward movements and seizures—and kept all treated mice alive. By contrast, about half of untreated mice and 15 percent of GNC92H2-treated mice died.

In a test that better simulated a real-life emergency situation, mice were first given a cocaine overdose, and three minutes later were infused with GNCgzk. About half of untreated mice were killed by such a dose. While GNC92H2 reduced that
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