Customizing monoclonal antibodies for the treatment of methamphetamine abuse: current and future applications.
Monoclonal antibody-based medications designed to bind (+)-methamphetamine (METH) with high affinity are among the newest approaches to the treatment of METH abuse and the associated medical complications. The potential clinical indications for these medications include treatment of overdose, reduction of drug dependence, and protection of vulnerable populations from METH-related complications. Research designed to discover and conduct preclinical and clinical testing of these antibodies suggests a scientific vision for how intact monoclonal antibody (mAb) (singular and plural) or small antigen-binding fragments of mAb could be engineered to optimize the proteins for specific therapeutic applications. In this review, we discuss keys to success in this development process including choosing predictors of specificity, efficacy, duration of action, and safety of the medications in disease models of acute and chronic drug abuse. We consider important aspects of METH-like hapten design and how hapten structural features influence specificity and affinity, with an example of a high-resolution X-ray crystal structure of a high-affinity antibody to demonstrate this structural relationship. Additionally, several prototype anti-METH mAb forms such as antigen-binding fragments and single-chain variable fragments are under development. Unique, customizable aspects of these fragments are presented with specific possible clinical indications. Finally, we discuss clinical trial progress of the first in kind anti-METH mAb, for which METH is the disease target instead of vulnerable central nervous system networks of receptors, binding sites, and neuronal connections.
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Eric C
EC
Peterson
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; Department of Anesthesiology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
W Brooks
WB
Gentry
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. Electronic address: mowens@uams.edu.
S Michael
SM
Owens
D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use*; D005544:Forecasting; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D008694:Methamphetamine / Q000009:adverse effects; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D008694:Methamphetamine
Drug abuse; Human; Methamphetamine; Monoclonal antibody; Preclinical studies; Rat