Treating cocaine addiction with viruses

Abstract

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.

Free Energy Perturbation (FEP) Simulation on the Transition States of Cocaine Hydrolysis Catalyzed by Human Butyrylcholinesterase and Its Mutants

“…[1][2][3][4]6 An alternative approach is to interfere with the delivery of cocaine to its receptors or accelerate its metabolism in the body. 4,[7][8][9][10][11][12][13][14][15][16][17] Butyrylcholinesterase (BChE), the principal plasma enzyme that catalyzes cocaine hydrolysis into its biologically inactive metabolites, is an ideal target for this purpose. There are some clear advantages of using this enzyme to accelerate the cocaine metabolism.…”

Inmunoprotección activa contra cocaína

“…[36][37][38][39] Janda et al 20 desarrollaron el bacteriófago GNC92H2-p-VIII, al cual se le modificaron las proteínas de superficie pVIII, con el fin de generar una especie de malla esponjosa capaz de capturar las moléculas de cocaína dentro del SNC. La inmunización (dos veces diariamente) de ratas, vía intranasal con el bacteriófago, atenuó significativamente la actividad locomotora, pero sólo para dosis bajas o medias de cocaína.…”

Nuevas vacunas contra la morfina-heroína

“…21,22 Como resultado de esta alteración significativa de "antagonismo farmacológico de permeación hematoencefálica de la droga", el valor reforzante placentero que ésta induce disminuye notablemente, lo cual reduce el porcentaje de recaídas al consumo 21,22 (figura 1). Esta estrategia farmacológica experimental de naturaleza "inmunoprotectora" ha demostrado ser un tratamiento con eficacia terapéutica para atenuar significativamente y/o inhibir las conductas de búsqueda y consumo adictivo a la cocaína, la nicotina y la morfina/heroína, tanto al nivel preclínico en el roedor [23][24][25][26][27][28][29][30][31][32] como en el humano. 33,34 Además es importante resaltar que dada la naturaleza del mecanismo farmacocinético antes descrito, relacionado con los efectos de la droga, al disminuirse significativamente la permeación de la droga hacia el tejido cerebral se bloquean los efectos reforzadores que induce la droga a nivel central, y además no se producen los efectos secundarios tóxicos colaterales generados a menudo con los fármacos clásicos empleados comúnmente contra los procesos de adicción.…”