About 7 million people worldwide are suffering from various inherited neuromuscular diseases. Gene therapy brings the hope of treating these diseases at their genetic roots. Muscle Gene Therapy is the only book dedicated to this topic. The first edition was published in 2010 when the field was just about to enter its prime time. The progress made since then has been unprecedented. The number of diseases that have been targeted by gene therapy has increased tremendously. The gene therapy toolbox is expanded greatly with many creative novel strategies (such as genome editing and therapy with disease-modifying genes). Most importantly, clinical benefits have begun to emerge in human patients. To reflect rapid advances in the field, we have compiled the second edition of Muscle Gene Therapy with contributions from experts that have conducted gene therapy studies either in animal models and/or in human patients. The new edition offers a much needed, up-to-date overview and perspective on the foundation and current status of neuromuscular disease gene therapy. It provides a framework to the development and regulatory approval of muscle gene therapy drugs in the upcoming years. This book is a must-have for anyone who is interested in neuromuscular disease gene therapy including those in the research arena (established investigators and trainees in the fields of clinical practice, veterinary medicine and basic biomedical sciences), funding and regulatory agencies, and patient community.

Autorentext

Dongsheng Duan, Ph.D., is the Margaret Proctor Mulligan Professor in Medical Research, at the Department of Molecular Microbiology & Immunology, Neurology, Bioengineering, and Biomedical Sciences at the University of Missouri.  He received his medical degree from the West China University of Medical Science, Chengdu, China in 1987 and his Ph.D. degree from the University of Pennsylvania, Philadelphia, USA in 1997.  His research in last two decades has focused on the development of adeno-associated virus as a gene therapy vector, pathogenic mechanisms of Duchenne muscular dystrophy, dystrophin biology and preclinical gene therapy for Duchenne muscular dystrophy in murine and canine models.

Jerry R Mendell, M.D. is the Curran-Peters Research Chair and Professor of Pediatrics and Neurology. His career has been devoted to translational clinical science, beginning as a post doctoral fellow at the National Institutes of Health.  His life-long focus has been to make a difference in lives burdened with untreatable neuromuscular disease. He has contributed significantly to the muscular dystrophies and spinal muscular atrophy, at first using pharmaceutical tools and since 1999, the time of his first gene therapy trial, he has been dedicated to the successful replacement of mutant genes that undermine the lives of innocent victims.

Zusammenfassung

Muscle disease represents an important health threat to the general population. Unlike diseases affecting other tissues/organs, therapeutic options are quite limited for many inherited muscle diseases such as Duchenne muscular dystrophy. There is essentially no cure. Gene therapy holds great promise to correct the genetic defects and eventually achieve full recovery in these diseases. Significant progresses have been made in the field of muscle gene therapy over the last few years. A variety of new strategies, such as exon-skipping and RNAi, have greatly expanded the scope of muscle gene therapy beyond the traditional gene replacement approach. The development of novel gene delivery vectors has substantially enhanced specificity and efficiency of muscle gene delivery. The new knowledge on the immune response to viral vectors has added new insight in overcoming the immune obstacles. Most importantly, the field has finally moved from small experimental animal models to human patients. This book will bring together the leaders in the field of muscle gene transfer to provide an updated overview on the progress of muscle gene therapy. It will also highlight important clinical applications of muscle gene therapy.

Inhalt

**Part 1 Foundations for muscle gene therapy.- **Chapter 1. An overview of muscle biology and physiology for muscle gene therapy.- Chapter 2. Molecular basis of muscle disease.- Chapter 3. Animal models for muscle disease and muscle gene therapy.- Chapter 4. Muscle stem cell biology and implication in gene therapy.- Chapter 5. Pluripotent stem cells for gene therapy of hereditary muscle disorders.- Chapter 6. MicroRNAs (miRs) in muscle gene therapy.- Chapter 7. Immune system regulation of muscle injury and disease.- Chapter 8. Design of muscle gene therapy expression cassette.- Chapter 9 Non-viral vector mediated muscle gene therapy.- Chapter 10. Viral vectors for muscle gene therapy.- Chapter 11. Development of next generation muscle gene therapy AAV vectors.- Chapter 12. Histological and biochemical evaluation of muscle gene therapy.- Chapter 13. Optical polarization tractography imaging of structural changes in the skeletal and cardiac muscles of the mdx4cv mice.- Chapter 14. Biomarkers for muscle disease gene therapy.- Chapter 15. Large-scale clinical manufacturing of AAV Vectors for systemic muscle gene therapy.- Chapter 16. Genome-editing for muscle gene therapy.- **Part 2 Preclinical muscle gene therapy.- **Chapter 17. Considerations on preclinical muscle gene therapy studies.- Chapter 18. Gene replacement therapy for Duchenne muscular dystrophy.- Chapter 19. Recent advances in AON-mediated exon-skipping therapy for Duchenne muscular dystrophy.- Chapter 20. AAV-mediated exon-skipping therapy for Duchenne muscular dystrophy.- Chapter 21. Alternate translational initiation of dystrophin: a novel therapeutic approach.- Chapter 22. Genome editing for Duchenne muscular dystrophy.- Chapter 23. Sarcolipin knockdown therapy for Duchenne muscular dystrophy.- Chapter 24. Gene therapy for central nervous system in Duchenne muscular dystrophy.- Chapter 25. Therapeutic approach for dysferlinopathy in animal models.- Chapter 26.  Muscle cell membrane repair and therapeutic implications.- Chapter 27. Treatment of muscular dystrophy-dystroglycanopathy: unlocking the potential of genetic engineering.- Chapter 28. RNAi therapy for dominant muscular dystrophies and other myopathies.- Chapter 29. Gene therapy for facioscapulohumeral muscular dystrophy (FSHD).- Chapter 30. Gene therapy and gene editing for myotonic dystrophy.- Chapter 31. Gene therapy for oculopharyngeal muscular dystrophy.- Chapter 32. Gene therapy for X-linked myotubular myopathy.- Chapter 33. Pre-clinical gene therapy studies for metabolic myopathy.- Chapter 34 Elimination of mutant mitochondrial DNA in mitochondrial myopathies using gene editing enzymes.- Chapter 35. Gene therapy for Charcot-Marie-Tooth inherited neuropathy.- Chapter 36. Muscle - a potent target in vaccination.- Part 3 Clinical muscle gene therapy.- Chapter 37. Patient and family perspective on muscle gene therapy.- Chapter 38. Design of clinical trials for gene therapy in muscular dystrophy.- Chapter 39. Path to clinical trials: trial design, development of the clinical product and safety concerns in the implementation of clinical trials.- Chapter 40. Muscle MRI as an endpoint in clinical trials.- Chapter 41. Gene therapy clinical trials for Duchenne and limb girdle muscular dystrophies lessons learned.- Chapter 42. Duchenne muscular dystrophy exon-skipping trials.- Chapter 43. What we have learned from 10 years of DMD exon skipping trials.- Chapter 44. Clinical gene therapy trials for Pompe disease.- Chapter 45. Muscle-directed gene therapy for alpha-1 antitrypsin deficiency.