Cocaine and Butyrylcholinesterase Gene Therapy

This chapter briefly describes the promise of mutated versions of butyrylcholinesterase (BChE), a metabolic enzyme altered to treat cocaine addiction. BChE has been engineered into a highly efficient cocaine hydrolase (CocH) that inactivates cocaine within seconds after its appearance in the bloodstream, thus barring drug access to brain reward centers. Studies in rodent models have shown that CocH not only prevents cocaine's stimulant and rewarding effects but also averts seizures and death from normally lethal cocaine overdoses. CocH expressed by adenoviral gene transfer vector enables durable and effective levels of enzyme expression in liver and plasma. Recent efforts at the Mayo Clinic are focusing on accumulating preclinical evidence of safety and, ultimately, advancing this therapy into human trials.