Treatments from Toxins: The Therapeutic Potential of Clostridial Neurotoxins, 1st Edition (Hardback) book cover

Treatments from Toxins

The Therapeutic Potential of Clostridial Neurotoxins, 1st Edition

Edited by Keith Alan Foster, Peter Hambleton, Clifford C. Shone

CRC Press

312 pages | 11 Color Illus. | 38 B/W Illus.

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Description

As little as two decades ago, deliberately injecting botulinum toxin into patients would have seemed foolhardy at best and criminal at worst. The increased clinical use of botulinum toxins has expanded the body of knowledge available on the structure and function of these proteins. This knowledge can be applied to topics as varied as therapies based on the endopeptidase activity of the toxins, vaccine development, protection against botulism, and vectors for neuronal drug delivery. Based on recent scientific and clinical information from top international authorities, Treatments from Toxins: The Therapeutic Potential of Clostridial Neurotoxins reviews the status of current research and development and identifies significant developments.

Drawing on their vast experience in this field, the editors present the basic background of the bacteriology and genetics of the neurotoxigenic clostridia, a history of the discovery of the neurotoxins, and an overview of the tetanus and botulism diseases. The chapters detailing common medical applications of the toxins cover side effects and novel uses, including neuronal drug delivery strategies, and provide a fresh look at what can still be achieved. They also explore the toxins as potential threat agents and the advent of the therapeutic use of botulinum toxins. Highlighting the pitfalls, successes, and challenges that exist when engineering complex proteins, the book brings together the clinical and theoretical worlds. It presents a broad overview of the current status of botulinum research and its clinical applications.

Table of Contents

INTRODUCTION AND HISTORICAL PERSPECTIVE, K.A. Foster, P. Hambleton, and C.C. Shone

Introduction

Neurotoxigenic Clostridia

Diseases of Botulinum and Tetanus Neurotoxins

Clinical Use of Botulinum Neurotoxins

THREE-DIMENSIONAL PROTEIN STRUCTURES OF LIGHT CHAINS OF BOTULINUM NEUROTOXIN SEROTYPES A, B, AND E AND TETANUS NEUROTOXIN, S. Swaminathan and R.C. Stevens

Structure of Botulinum Neurotoxin 150kDa Holotoxin

Proteolysis of Snare Proteins by Botulinum Neurotoxin Light Chains

Structure of Botulinum Neurotoxin Serotype A Light Chain

Strucuture of Botulinum Neurotoxin Serotype B Light Chain

A Possible Proteolytic Mechanism of Botulinum Neurotoxins

Strudture of Botulinum Neurotoxin Light Chain E

Structure of Tetanus Neurotoxin Light Chain

Conclusion

References

MECHANISMS OF ACTIONS OF NEUROTOXINS, H. Bigalke and T. Binz

Introduction

Toxin Uptake, Toxicity, and Clinical Disease Manifestation

Binding to Nerve Cell Receptors

Internalization into the Neuronal Cytosol

References

VACCINES TO PROTECT AGAINST NEUROTOXINS, L.A. Smith and I. Henderson

Introduction

Toxoid Vaccines

Recombinant Vaccines

The Vaccine Candidate RBV A/B

Conclusion

References

INHIBITORS OF CLOSTRIDIAL NEUROTOXIN PROTEINASE ACTIVITIES, J.J. Schmidt and K.A. Foster

Inhibitors if Clostridial Neurotoxin Proteinase Activities

Neutralizing Antibodies

Conclusion

References

INTRODUCTION TO CLINICAL USE OF BOTULINUM NEUROTOXINS, M.P. Barnes

Introduction

Theory of Clinical Use

Practical Aspects of Injection Technique

Longer Term Side Effects and Problems

Logistics and Cost

Dystonia

Spasticity

Conclusions

References

EXPANDING CLINICAL USES OF BOTULINUM NEUROTOXINS, A.P. Moore

Introduction

New Indications

The Future: Other Possible Indications and Speculation

Conclusions

DEVELOPMENT OF THERAPEUTICS BASED UPON CLOSTRIDIAL ENDOPEPTIDASE ACTIVITY, K.A. Foster and J.A. Chaddock

Introduction

Clostridial Neurotoxin Structure and Function: The 'Endopeptidase' Domain

Recombinant Expression of the LHN/A

Rationale for Use of the LHN Endopeptidase

Pain

The Potential Use of Neurotoxins Endopeptidase Fragments for Pain Releif

Alternative Therapeutic Possibilities

Conclusions

References

USE OF NEUROTOXINS AS DRUG DELIVERY SYSTEMS, P. Foran

Overview

Generation of Non-Toxic Derivatives Retaining Neuronal Targeting and Delivery Capabilities Using Classical Biochemical Mehtods or Recombinant Means

The Diverse Neuronal Targeting and Cell Trafficking Pathways Exerted by Clostridial Neurotoxins

In Vitro or In Vivo Neuronal Targeting Achievements Made Using Innocuous Derivatives: But Not Demonstrating Cytosolic Transfer

Achievements of Cell or Neuronal Targeting, as well as, Cytoplasmic Delivery of Foreign Cargos Using Innocuous Derivatives

Important Structural Features Proven Essential For Efficient In Vivo Neuronal Targeting and Cytoplasmic Delivery of Cargo

Strategies for the Efficient Linkage of Therapeutic Adducts to Transporters: Approaches that Ensure Optimal Linkage Efficiency and Orientation

Potential Diseases that May be Targeted Using Innocuous BoNT- or TeNT-based Neuron Delivery Vehicles

How Much Cargo can BoNT-Based Transporters Deliver?

The Varied Intracellular Trafficking and Site-Specific Delivery Addresses Anticipated for Cargos Linked to BoNT-or TeNT-based Vehicles

Conclusion

References

CONCLUSIONS AND FUTURE PERSPECTIVES: BOTULINUM NEUROTOXINS AS PARADIGMS FOR DEVELOPMENT OF MICROBIAL EFFECTOR-DERIVED DRUGS, J.M. Sutton

Introduction

To Kill or Not to Kill: Strategies for Toxin Therapeutics

General Themes for the Future Development of Bacterial Effector-Based Therapeutics

References

Index

Subject Categories

BISAC Subject Codes/Headings:
MED071000
MEDICAL / Pharmacology
MED096000
MEDICAL / Toxicology
SCI089000
SCIENCE / Life Sciences / Neuroscience