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Discovery and Development of an Anti-methamphetamine Monoclonal Antibody for Use in Treating Methamphetamine Abuse

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Biologics to Treat Substance Use Disorders

Abstract

Anti-methamphetamine monoclonal antibodies (mAb) can reduce the pharmacological effects of methamphetamine (METH) in rodent models of METH abuse. Rather than a direct action in the brain, the mAb medication binds METH with high affinity in the bloodstream leading to a reduction and slowing of METH brain penetration. Through an extensive discovery and development process, prototype mouse anti-METH mAb medications were selected and tested in preclinical studies to select a final mAb with both high affinity for METH and long-term functionality in vivo. This antibody was then converted into a chimeric anti-METH mAb suitable for human use. In a Phase 1a clinical trial, the medication proved safe, with a half-life of 18 days. Because of this prolonged half-life, patients might only need mAb treatment once every 3 weeks to aid in the protection from relapse to METH abuse. Additional safety and efficacy will be tested in future clinical trials.

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Abbreviations

AMP:

(+)-amphetamine (unless denoted as other stereoisomer)

AUC:

area under the concentration-time curve

Bmax :

maximum number of binding sites

ch:

chimeric

Css, Cmin, Cmax :

denotes the steady-state, minimum, and maximum concentrations during chronic administration of a drug

ECG:

electrocardiograms

ELISA:

enzyme-linked immunosorbent assay

FcRn:

Fc receptor of the neonate

HACA:

human anti-chimeric antibodies

IgG:

immunoglobulin G

iv:

intravenous

Kd :

dissociation constant

mAb:

monoclonal antibody (both singular and plural)

KI :

inhibition constant

MCV:

METH-conjugate vaccine

MDMA:

(+/−)-methylenedioxymethamphetamine (unless denoted as other stereoisomer)

METH:

(+)-methamphetamine (unless denoted as other stereoisomer)

t1/2 :

half-life

sc:

subcutaneous

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Funding Sources

Research funding was provided by the National Institutes of Health; the National Institute on Drug Abuse Grants DA11560, DA028915, and DA031944; the National Center for Advancing Translational Sciences (Grant ULITR000039); and the Arkansas Biosciences Institute (the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000).

Notes

S. Michael Owens and W. Brooks Gentry are Chief Scientific Officer and Chief Medical Officer, respectively, and have financial interests in InterveXion Therapeutics, LLC, a pharmaceutical biotech company, whose main interest is the development of antibody medications for the treatment of human diseases, including drug abuse.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

    Michael D. Hambuchen, Melinda G. Gunnell, W. Brooks Gentry & S. Michael Owens

  2. InterveXion Therapeutics, LLC, Little Rock, AR, 72205, USA

    Misty W. Stevens

  3. Department of Anesthesiology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

    W. Brooks Gentry

Authors
  1. Michael D. Hambuchen
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  2. Misty W. Stevens
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  3. Melinda G. Gunnell
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  4. W. Brooks Gentry
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  5. S. Michael Owens
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Corresponding author

Correspondence to S. Michael Owens .

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Editors and Affiliations

  1. National Institute on Drug Abuse, National Institutes of Health, Bethesda, USA

    Ivan D. Montoya

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Hambuchen, M.D., Stevens, M.W., Gunnell, M.G., Gentry, W.B., Owens, S.M. (2016). Discovery and Development of an Anti-methamphetamine Monoclonal Antibody for Use in Treating Methamphetamine Abuse. In: Montoya, I. (eds) Biologics to Treat Substance Use Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-23150-1_9

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  • DOI: https://doi.org/10.1007/978-3-319-23150-1_9

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