Clinical potential of a rationally engineered enzyme for treatment of cocaine dependence: Long-lasting blocking of the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine

Ting Zhang, Huimei Wei, Jing Deng, Fang Zheng, Chang Guo Zhan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

It is a grand challenge to develop a truly effective treatment of substance use disorder (SUD), particularly for cocaine and other drugs without an FDA-approved treatment available, because a truly effective therapy must effectively block the drug's physiological and reinforcing effects during the entire period of treatment in order to achieve the long-time abstinence required by the FDA. Whether a biologic, such as monoclonal antibody, vaccine, or therapeutic enzyme, can be truly effective for SUD treatment or not has been the subject of extensive debate. The main debate question is whether a biologic, particularly an exogenous enzyme, can effectively block the drug's reinforcing effect. In this report, we demonstrate that a modest dose of a recently redesigned long-acting cocaine hydrolase, CocH3-Fc(M6), can be used to effectively block the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine for a sufficiently long period of time. For example, a dose of 3 mg/kg CocH3-Fc(M6) completely blocked the discriminative stimulus and reinforcing effects for 24/25 days and continued to significantly attenuate/decrease the cocaine effects for at least 29 days in rats. All the animal data consistently suggest that the long-acting cocaine hydrolase is a truly promising candidate of enzyme therapy for treatment of cocaine use disorder.

Original languageEnglish
Article number108251
JournalNeuropharmacology
Volume176
DOIs
StatePublished - Oct 1 2020

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health (NIH grants UH2/UH3 DA041115 , R01 DA035552 , R01 DA032910 , R01 DA013930 , and R01 DA025100 ) and the National Science Foundation (NSF grant CHE-1111761 ).

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Cocaine
  • Cocaine hydrolysis
  • Cocaine metabolism
  • Drug abuse
  • Enzyme therapy

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Clinical potential of a rationally engineered enzyme for treatment of cocaine dependence: Long-lasting blocking of the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine'. Together they form a unique fingerprint.

Cite this