Spinal Muscular Atrophy

Disease Mechanisms and Therapy

Charlotte J Sumner, Sergey Paushkin, Chien-Ping Ko

• Publisher: Academic Press
• Year: 2016
• Print ISBN: 9780128036853
• eBook ISBN: 9780128036860
• Topic: Medicine
• Subtopic: Neurology

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 development - Written to bridge multiple disciplines and promote better communications among basic scientists, clinical researchers, and health care providers on the latest developments in SMA - Includes outstanding questions and perspectives for future investigations and key references for additional detailed study

Appendix 1

SMA Types, Summary

Table A1.1

SMA Types, Summary (Chapter 1, Table 1.1)

SMA Type	Age of Onset	Highest Motor Milestone	SMN2 Copy Number	Lifespan
IA	<1 week	Never sits	1	<1 month
IB	1 week–3 months	Never sits	2, 3	<2 years
IC	3–6 months	Never sits	2, 3	<2 years
IIA	6–15 months	Sits independently	3, 4	>2 years
		Loses the ability to sit
IIB	6–15 months	Sits independently	3, 4	>2 years
		Maintains the ability to sit
IIIA	<3 years	Walks independently	3, 4	Adult
IIIB	>3 years	Walks independently	3, 4	Adult
IV	>21 years	Walks independently	4–5	Adult

Appendix 2

SMN1 and SMN2 Copy Numbers of Commercially Available Spinal Muscular Atrophy Fibroblast and Lymphoblastoid Cell Lines

M.E.R. B...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Perspectives
• Sixty Years of Spinal Muscular Atrophy: A Personal Odyssey
• Advances in Spinal Muscular Atrophy Research
• From Mapping Survival Motor Neuron to Treatment of Spinal Muscular Atrophy
• The Path to Therapeutics Development for Spinal Muscular Atrophy
• Section I. Clinical Features and Diagnosis of SMA
• Section II. Cellular and Molecular Mechanisms of the Disease
• Section III. Cell and Animal SMA Models
• Section IV. Therapeutic Development
• Section V. Clinical Research
• Appendix 1. SMA Types, Summary
• Appendix 2. SMN1 and SMN2 Copy Numbers of Commercially Available Spinal Muscular Atrophy Fibroblast and Lymphoblastoid Cell Lines
• Appendix 3. Transacting Factors and cis-Elements Involved in Modulation of SMN2 Exon 7 Alternative Splicing
• Appendix 4. Sequence Alignment of the SMN Proteins From Diverse Organisms and List of SMN1 Mutations Identified in Humans
• Appendix 5. SMN Role in the snRNP Assembly
• Appendix 6. Select SMN-Dependent and SMN-Independent Modifiers
• Appendix 7. Mouse Models of SMA and Mice Used in SMA Research
• Appendix 8. SMA Strains for Testing Site-Specific Smn Expression
• Appendix 9. Functional Scales Used in SMA
• Appendix 10. Select SMA Organizations Around the World
• Index