Biologics to Treat Substance Use Disorders: Vaccines, Monoclonal Antibodies, and Enzymes PDF
Preview Biologics to Treat Substance Use Disorders: Vaccines, Monoclonal Antibodies, and Enzymes
Biologics to Treat Substance Use Disorders Vaccines, Monoclonal Antibodies, and Enzymes Ivan D. Montoya Editor 123 Biologics to Treat Substance Use Disorders Ivan D. Montoya Editor Biologics to Treat Substance Use Disorders Vaccines, Monoclonal Antibodies, and Enzymes Editor Ivan D. Montoya National Inst Drug Abuse, Room 4131 National Institutes of Health Bethesda , MD USA ISBN 978-3-319-23149-5 ISBN 978-3-319-23150-1 (eBook) DOI 10.1007/978-3-319-23150-1 Library of Congress Control Number: 2015957970 Springer Cham Heidelberg New York Dordrecht London © Springer International Publishing Switzerland 2016 T his work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. T he use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. T he publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) Foreword T he treatment of drug use disorders (DUDs) is challenging because of the clinical nature of these entities and the limited number and effi cacy of available pharmaco- therapies. Biologics such as vaccines, monoclonal antibodies, and enzymes offer new alternative therapeutic strategies. The aim for these interventions is to prevent the entry of the drug to the brain and thus interfere with its rewarding and neuro- toxic effects. This book is the fi rst comprehensive compendium of research in the development of biologics to treat DUDs and drug overdose. Most of the preclinical and clinical work on biologics discussed in this book has been supported by NIDA as part of its commitment to the discovery and development of new treatments. In the development of drug vaccines, a major challenge has been the generation of suffi ciently high titers of antibodies to bind to the high concentrations of the drug in the blood of those taking them. As of now, clinical trials with nicotine and cocaine vaccines have been disappointing, but research for the development of vaccines with higher antigenicity is ongoing. Passive immunization with monoclonal anti- bodies allows the delivery of suffi ciently high antibody titers to counteract the drug’s effects and thus offers an intervention with which to treat patients who over- dose with drugs such as heroin, oxycodone, nicotine, cocaine, or methamphetamine. Research is ongoing for the development of strategies to sustain high levels of monoclonal antibodies so that they can also be used as potential treatments of addic- tion (methamphetamine, cocaine). Finally, enzymes aimed at accelerating the metabolism of a drug might also be helpful in the treatment of overdoses and when combined with monoclonal antibodies or vaccines might help boost their therapeu- tic potential. Similarly as advances emerge on other therapeutic intervention for DUD, one can foresee that their combined use with biologics will help improve clinical out- comes in those affl icted with DUD. This volume will present the reader with a sum- mary of the advances and challenges in the use of biologics for DUD. Bethesda, MD, USA Nora Volkow National Institute on Drug Abuse (NIDA) v Pref ace S ubstance use disorders (SUDs), including alcohol and drug use disorders (DUDs), are a global public health concern with less than optimal treatment outcomes. There are medications approved by regulatory agencies to treat nicotine (i.e., bupropion, nicotine replacement therapies, and varenicline) and opioid (buprenorphine, metha- done, and naltrexone) use disorders. There are no approved medications for cocaine, methamphetamine, and cannabis use disorders, despite more than 25 years of research and multiple medications evaluated (Montoya and Vocci 2008). Moreover, a small proportion of patients with DUDs who received treatment are able to stop using drugs, but most relapse. Therefore, there is a high need to discover safe and effective medications to treat these disorders. T raditionally, medications development for DUDs has focused on small mole- cules that cross the blood-brain barrier, have their effect on molecular targets in the brain, and produce changes in brain circuits. These changes are expected to modify the patient’s drug use. A new therapeutic approach for DUDs is with biologics such as vaccines, monoclonal antibodies, and enzymes. Biologics are large molecules that do not cross the blood-brain barrier and thus have no CNS effects. The main mechanism of action is a pharmacokinetic antagonism in which the biologic pre- cludes the access of drugs of abuse to the brain. They target the molecule responsi- ble for the DUD peripherally and change its metabolism, distribution, or clearance. As a result, biologics can prevent the reinforcing and neurotoxic effects of drugs and protect against drug use relapse (Montoya 2012). B iologics have shown an enormous public health benefi t and are making a sig- nifi cant impact in many areas of medicine, such as in oncology, rheumatology, der- matology, neurology, and psychiatry, including DUDs. Currently, there are no biologics approved by the FDA to treat DUDs. Potential clinical indications might prevent the initiation of drug use and progression from drug use experimentation to addiction. The current research is focused on treating DUDs and drug overdose (Gorelick 2012). New products and more effi cient methods of production are offering vast oppor- tunities to advance the discovery and development of biologics against drugs of vii viii Preface abuse. In addition, as the fi eld expands, more investigators from different areas of expertise are becoming involved in the development of biologics to treat DUDs. Given the rapid progress of this area of research, in 2013 the National Institute on Drug Abuse (NIDA) hosted a meeting that brought together academic investigators, industry representatives, research sponsors, regulators, and government representa- tives to review the current status of research in the fi eld and to make recommenda- tions to NIDA as to how product development might be accelerated. T he meeting participants identifi ed scientifi c gaps, opportunities, and direc- tions and developed multiple research collaborations. It became evident that bio- logics to treat DUDs is a new fi eld with multiple challenges. They include determining the agent’s potency, preclinical testing requirements, optimal dosing and schedules, translation from preclinical to clinical, appropriate clinical trial design, and pattern of therapeutic response. The meeting was very successful; most of the authors of this book participated in this meeting and the topics are covered in this book. T his book starts with a general introduction, followed by a review of the research on vaccines against nicotine, cocaine, opioids, and methamphetamine use disorders. Then, there is an introduction to monoclonal antibodies and separate chapters to discuss the anti-cocaine and anti-methamphetamine monoclonal anti- bodies for the treatment of the respective disorders and drug overdose. The next section discusses the enzyme-based treatments for DUDs, including a butyrylcho- linesterase that was recently evaluated to treat cocaine dependence in a phase II/III clinical trial. The fourth section reviews a variety of topics about strategies to optimize the development of biologics to treat DUDs. It includes, for example, adenovirus- and nanoparticle-based vaccines, new adjuvants, hapten design, cell mechanisms of vaccine effi cacy, and skin vaccination. The last section includes some practical and ethical considerations for the development of vaccines against drugs of abuse. T his is the fi rst and most comprehensive book about the research and develop- ment of biologics to treat DUDs and drug overdose. Its goal is to promote interest and advance the scientifi c knowledge of anti-drug biologics. The hope is that studies will show that biologics are safe and effective and can be approved by the FDA to treat these challenging medical conditions. Ideally, biologics will be part of the therapeutic armamentarium that health-care providers can prescribe to patients whose brains have been hijacked by drugs and to save the lives of those who over- dosed with drugs. M y deepest gratitude goes to all the authors who enthusiastically contributed to this book. Without their support, this book would not have been possible. I want to thank Dr. Jamie Biswas, Chief of the Medications Research Branch of NIDA, for introducing me to the fi eld of biologics to treat DUDs and Dr. Nora Chiang, Chief of the Chemistry and Pharmaceutics Branch of NIDA, for her suggestions to the content and authors of the book. I also want to thank the editors at Springer for their support in developing this book. Finally, I am very grateful to my wife, Martha Velez, and my daughter Lina, who make it all worthwhile. Bethesda, MD, USA Iván D. Montoya Preface ix References Gorelick DA. Pharmacokinetic strategies for treatment of drug overdose and addiction. Future Med Chem. 2012;4:227–43. Montoya ID. Advances in the development of biologics to treat drug addictions and overdose 1. Adicciones. 2012;24:95–103. Montoya ID, Vocci F. Novel medications to treat addictive disorders. Curr Psychiatry Rep. 2008;10:392–8.
Description:The list of books you might like
