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November 2010 Issue

W. James Ball, PhD (left), and Andrew Norman, PhD.
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Research Targets Cocaine Addiction

Published November 2010

Cocaine has wreaked social devastation for decades, destroying lives and costing society billions of dollars.
Now, research is under way on two fronts at UC into the possibility of ending cocaine addiction through injectible therapies.

Cincinnati is one of six sites nationwide participating in a vaccine designed to treat cocaine addiction by preventing the drug from entering the brain. Eugene Somoza, MD, PhD, is the principal investigator of the Cincinnati study, which is being conducted at the Cincinnati Department of Veterans Affairs Medical Center.

At the same time, Andrew Norman, PhD, and W. James Ball, PhD, are collaborating on research into a potential immunotherapy for cocaine addiction. Norman recently was awarded $2.5 million over five years from the National Institute on Drug Abuse (NIDA) to support that work.

"There are currently no Food and Drug Administration-approved therapies for cocaine addiction,” says Somoza, a professor in the department of psychiatry and behavioral neuroscience. The phase 2 trial under way in Cincinnati and elsewhere is testing the efficacy of TA–CD (Therapy for Addiction–Cocaine Dependence), whose patent is owned by the international private equity firm Celtic Parma.

Somoza notes that traditional immunotherapy targets involve complex molecules considered foreign by the body’s immune system, which develops specific antibodies against them. Cocaine is a simple molecule, and can only trigger the immune system by attaching to a complex molecule. When this happens, the immune system produces antibodies against cocaine just as it does when viral or bacterial proteins that enter the body.

As a result, when vaccinated patients use cocaine and its molecules reach the bloodstream, they are immediately sequestered by the antibodies—which hold on tightly to them, thus preventing them from entering the brain where they produce their deleterious effects.

"Addiction is dependent on how quickly the substance gets to the brain,” Somoza says. "So by slowing down or stopping the process, it would be possible to decrease the pleasurable effect individuals get from cocaine.”

Norman, a professor in the psychiatry and behavioral neuroscience department, was one of four winners of the NIDA’s first Translational Avant-Garde Awards for Innovative Medication Development Research. Award winners receive $500,000 per year for five years to support their research.

Norman and Ball, a professor in the department of pharmacology and cell biophysics department, are working on the development of a human monoclonal antibody (an antibody derived from a single cell for use against a specific target) against cocaine. Such an antibody, when injected into the bloodstream, would attach to cocaine, preventing it from entering the brain and thereby limiting its behavioral effects.

This humanized monoclonal antibody has previously been shown by Norman and Ball to reduce cocaine’s effects in an animal model of relapse. Such an immunotherapy, by directly injecting the antibody, would therefore not rely on having the immune system develop antibodies against cocaine.

The research teams stay in touch with each other, and Somoza notes that the differing treatments have the potential to be synergistic.

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