Spinal Muscular Atrophy: Disease Mechanisms and Therapy

Spinal Muscular Atrophy: Disease Mechanisms and Therapy provides the latest information on a condition that is characterized by motoneuron loss and muscle atrophy, and is the leading genetic cause of infant mortality. Since the identification of the gene responsible for SMA in 1995, there have been important advances in the basic understanding of disease mechanisms, and in therapeutic development.

This book provides a comprehensive accounting of recent advances in basic and clinical research that covers SMA clinical features and standards of care, multifaceted aspects of SMN protein functions and SMA disease pathology, various animal models, and biomarkers, as well as current therapeutic development.

This title is ideal for graduate students/postdocs and principal investigators who are already in the SMA field and need to keep updated on recent findings and approaches, and for those who are new to, or would like to join, the field. Likewise, users will find an excellent source of reading for biotech/pharma scientists, clinical researchers, and practitioners, regulators, and patients and their advocacy organizations. Furthermore, this book is a handy reference for researchers and clinicians who may want to apply the research strategies and therapeutic approaches in SMA to other rare diseases.

Provides comprehensive, up-to-date reviews by leading investigators on diverse topics of SMA, including clinical features and patient care, SMN genetics and protein functions, animal models, disease pathology and mechanisms, biomarkers, current therapeutic development, and the role of non-profit organizations in therapeutic developmentWritten to bridge multiple disciplines and promote better communications among basic scientists, clinical researchers, and health care providers on the latest developments in SMAIncludes outstanding questions and perspectives for future investigations and key references for additional detailed study

Section I. Clinical Features and Diagnosis of SMA 1. Spinal Muscular Atrophy: 125 Years Later and on the Verge of a Cure 2. Developmental Aspects and Pathological Findings in Spinal Muscular Atrophy 3. Standard of Care for Spinal Muscular Atrophy 4. Strategy for the Molecular Testing of Spinal Muscular Atrophy

Section II. Cellular and Molecular Mechanisms of the Disease 5. Transcriptional and Splicing Regulation of Spinal Muscular Atrophy Genes 6. The Function of Survival Motor Neuron Complex and Its Role in Spinal Muscular Atrophy Pathogenesis 7. RNA-Processing Dysfunction in Spinal Muscular Atrophy 8. Axonal and Neuromuscular Junction Pathology in Spinal Muscular Atrophy 9. Motor Circuit Dysfunction in Spinal Muscular Atrophy 10. Contributions of Different Cell Types to Spinal Muscular Atrophy Pathogenesis 11. Temporal Requirements for the Survival Motor Neuron Protein 12. Spinal Muscular Atrophy Disease Modifiers

Section III. Cell and Animal SMA Models 13. Cell Culture Models of Spinal Muscular Atrophy 14. Nonmammalian Animal Models of Spinal Muscular Atrophy 15. Mammalian Models of Spinal Muscular Atrophy

Section IV. Therapeutic Development 16. Spinal Muscular Atrophy Therapeutics Development 17. Small Molecule Approaches to Upregulate SMN Expression From the SMN2 Locus 18. Antisense-Oligonucleotide Modulation of SMN2 Pre-mRNA Splicing 19. Gene Transfer in Spinal Muscular Atrophy 20. Neuroprotection As a Therapeutic Approach for Spinal Muscular Atrophy 21. Skeletal Muscle in Spinal Muscular Atrophy As an Opportunity for Therapeutic Intervention 22. Addressing Cell Therapy for Spinal Muscular Atrophy: Open Issues and Future Perspectives

Section V. Clinical Research 23. Spinal Muscular Atrophy Motor Functional Scales and Measures of Pulmonary Function 24. Development and Testing of Biomarkers in Spinal Muscular Atrophy 25. Natural History of Spinal Muscular Atrophy 26. Spinal Muscular Atrophy Clinical Trials: Lessons Learned