January 24, 2008

Minnesota Partnership Team Finds Cocaine Antidote
Wins $1.5 million federal research award

MINNEAPOLIS/ROCHESTER, Minn. -- After only one year of collaboration, a Minnesota Partnership team has discovered a therapy that blocks cocaine poisoning in animal models. As a result, they garnered a $1.5 million grant from the National Institutes of Health (NIH) to translate those findings to humans. The team has just published their findings online in the Nature journal publication, Neuropsychopharmacology (http://www.nature.com/npp/index.html).

Using a 2006 grant from the Minnesota Partnership for Biotechnology and Medical Genomics, Stephen Brimijoin, Ph.D., Mayo Clinic, and Marilyn Carroll, Ph.D., University of Minnesota, found that a modified human plasma-enzyme stopped convulsions in rats that were administered a normally lethal dose of cocaine. The rats survived even though the enzyme -- CocH (cocaine hydrolase) -- was administered after the cocaine had already induced severe toxicity. The study further showed that CocH also stopped rats that were addicted to cocaine from relapsing when given that drug again.

"The Minnesota Partnership gave us the initial start and motivation to move forward and make these groundbreaking steps in the fight against cocaine addiction,” says Dr. Brimijoin. "It spurred us to continue to combine our complementary strengths and apply for the NIH grant." The award came after the team’s first application, which is unusual given the highly competitive state of NIH funding.

One of today’s most serious health problems, the risk of cocaine addiction is high after even a brief period of casual use, and recovery from addiction is extremely difficult. Building on their work that helped engineer "cocaine-eating” enzymes -- new enzymes that destroy cocaine so quickly it cannot act on the brain or other targets -- Drs. Brimijoin and Carroll are seeking to make this technology safe for humans. They say their findings should provide realistic options for therapies against cocaine overdose and abuse.

"Relapse is a critical component of the study since chronically recurring drug abuse is a major challenge to treatment,” says Dr. Carroll. "Most individuals who undergo treatment for addiction have nearly an 80 percent chance of relapse, even after long periods of abstinence.”

The NIH grant will allow the investigators to build on their Minnesota Partnership work by studying "metabolic therapy” for cocaine overdose and the critical stages of cocaine addiction.

The research is based on the premise that one or more of several gene-transfer approaches will suppress drug-seeking behavior in addicted rats and also reduce the propensity for relapse. Previous attempts to block drug-seeking behavior have used dopamine receptor antagonists that have many side effects. In contrast, this proposed treatment appears to have no side effects at doses that suppress drug-seeking behavior. The results should increase understanding of the biology of abuse and test the concept that cocaine abuse might be effectively treated by methods that prevent drug access to targets in the brain.

The Minnesota Partnership for Biotechnology and Medical Genomics is a collaboration among the University of Minnesota, Mayo Clinic and the State of Minnesota. To learn more about the Partnership, go to http://www.minnesotapartnership.info.

Read more about the research team.

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