Neuromuscular Autoimmune Disorders

I Lieberburg, T Yednock, S Freedman, R Rydel, and E Messersmith, Elan Pharmaceuticals, South San Francisco, CA, USA R Tuttle, EI Cerrito, CA, USA

© 2007 Elsevier Ltd. All Rights Reserved.

6.09.1 Introduction 230

6.09.2 Autoimmune Diseases 232

6.09.2.1 Diseases Affecting the Central Nervous System 232 6.09.2.1.1 Multiple sclerosis 232

6.09.2.2 Diseases Affecting Both the Central Nervous System and Peripheral

Nervous System 233

6.09.2.2.1 Systemic lupus erythematosus 233

6.09.2.3 Diseases Affecting the Peripheral Nervous System 234

6.09.2.3.1 Guillain-Barre syndrome 234

6.09.2.3.2 Chronic inflammatory demyelinating polyradiculoneuropathy 235

6.09.2.3.3 Myasthenia Gravis 236

6.09.2.4 Candidate Autoimmune Diseases 236 6.09.2.4.1 Amyotrophic lateral sclerosis 236

6.09.3 Experimental Animal Models 237

6.09.3.1 Overview 237

6.09.3.2 Disease-Specific Animal Models 239

6.09.4 Clinical Trial Issues 242

6.09.5 Treatment Challenges 242

6.09.6 Biological Treatments 243

6.09.6.1 Selective Adhesion Molecule Inhibitors 243

6.09.6.2 Anti-Inflammatory Cytokines 244

6.09.6.3 Proinflammatory Cytokines and Their Receptors 244

6.09.6.4 B and T Cell Targets 245

6.09.6.4.1 B and T Cell depletion mechanisms 245

6.09.6.4.2 Co-stimulatory molecule inhibitors 245

6.09.6.5 Therapeutic Vaccines and Toleragens 246

6.09.6.6 Statins 246

6.09.6.7 Corticosteroids 246

6.09.7 Other Treatment Strategies 247

6.09.7.1 Intravenous Immunoglobulin and Plasma Exchange 247

6.09.7.2 Stem Cell Therapy 247

6.09.7.3 Gene Therapy 247

6.09.8 Disease-Specific Treatment Strategies 248

6.09.8.1 Multiple Sclerosis 248

6.09.8.2 Systemic Lupus Erythematosus 248

6.09.8.3 Guillain-Barre Syndrome 248

6.09.8.4 Chronic Inflammatory Demyelinating Polyradiculoneuropathy 249

6.09.8.5 Myasthenia Gravis 249

6.09.9 The Future 250 References 250

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