>>Published online before print June 28, 2004
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0403795101
Medical Sciences
Treating cocaine addiction with viruses
M. Rocio A. Carrera *, Gunnar F. Kaufmann *, Jenny M. Mee *, Michael M. Meijler *, George F. Koob , and Kim D. Janda *
Departments of *Chemistry and Neuropharmacology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037
Communicated by Sydney Brenner, The Salk Institute for Biological Studies, La Jolla, CA, May 27, 2004 (received for review May 8, 2004)
Cocaine addiction continues to be a major health and social problem in the United States and other countries. Currently used pharmacological agents for treating cocaine abuse have proved inadequate, leaving few treatment options. An alternative is to use protein-based therapeutics that can eliminate the load of cocaine, thereby attenuating its effects. This approach is especially attractive because the therapeutic agents exert no pharmacodynamic action of their own and therefore have little potential for side effects. The effectiveness of these agents, however, is limited by their inability to act directly within the CNS. Bacteriophage have the capacity to penetrate the CNS when administered intranasally. Here, a method is presented for engineering filamentous bacteriophage to display cocaine-binding proteins on its surface that sequester cocaine in the brain. These antibody-displaying constructs were examined by using a locomotor activity rodent model to assess the ability of the phage-displayed proteins to block the psychoactive effects of cocaine. Results presented demonstrate a strategy in the continuing efforts to find effective treatments for cocaine addiction and suggest the application of this protein-based treatment for other drug abuse syndromes.<<
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