Therapeutic Proteins Targeting Heroin Addiction Group IV Contingencies

Therapeutic Proteins Targeting Heroin Addiction Group IV

Contingencies involved • Potentially efficacious therapeutic proteins should be able to bind its vast array of targets with high specificity and avoid interference with medicinal/endogenous opioids • Polyopioid addiction Development of a multifunctional protein • Current possibilities: – Vaccine production of anti-opioid subtances by the body – m. Ab Direct sequestration of opiods

Development of Vaccines • Vaccine Triggers Immune Response Antibodies Generated Heroin/Metabolites Destroyed • Morphine-Tetanus Toxoid (M-TT) Vaccine • Tetanus Toxoid Carrier Protein • Recombinant Polypeptide (Non-Toxic), designed from the H chain of the tetanus toxoid • Specificity for metabolites of heroin, but not for therapeutic opiate compounds (e. g. methadone) – 6 -MAM – M-6 -G – M-3 -G

Therapeutic Antibodies • Monoclonal Antibodies (m. Ab) • Most of heroin is metabolised into 6 -MAM under an hour in the body • Antibody sequestration of 6 -MAM prevents conversion to morphine • The aggregate is too large to cross the blood -brain barrier (BBB) • Half-life of m. Ab ~ 8 -9 days

References Bogen, I. L. , Boix, F. , Nerem, E. , Mørland, J. , & Andersen, J. M. (2014). A monoclonal antibody specific for 6 -monoacetylmorphine reduces acute heroin effects in mice. The Journal of Pharmacology, 349, 568 -576. doi: 10. 1124/jpet. 113. 212035 Anton, B. , & Leff, P. (2006). A novel bivalent morphine/heroin vaccine that prevents relapse to heroin addiction in rodents. Vaccine, 24, 3232– 3240. doi: 10. 1016/j. vaccine. 2006. 01. 047 Garrido, P. , Prat, A. , Crespo, I. , Lopez-Ortíz, C. , Lumbreras, D. , Bertran, V. , … Abades, J. J. (2013). Avances en el desarrollo de vacunas frente a sustancias adictivas (ii). Vacunas antiopiáceos. Otras vacunas. Vacunas. doi: 10. 1016/j. vacun. 2013. 10. 001