Viral Gene Transfer of Enzymes

Abstract

This chapter will address strategies for treating cocaine abuse with the aid of gene transfer vectors that drive long-sustained in vivo expression of a highly efficient cocaine hydrolase that reduces or prevents cocaine access to reward centers in the brain. A theoretical rationale for this approach will be presented first, followed by a brief survey of viral gene transfer in terms of risks and benefits from specific classes of agents that might be employed. Next will be evidence from rodent studies indicating that gene therapy with cocaine hydrolase is capable of suppressing drug reward to a point where mice and rats abandon opportunities to press levers for i.v. cocaine infusions. After that will come observations indicating that these desired effects can be achieved without discernible toxicity. Finally some practical issues are addressed in regard to ongoing interactions with the US FDA and the process of demonstrating levels of safety and efficacy that meet that agency’s standards to approve an initial clinical trial based on the concept of drug interception.