{"product_id":"spectrums-of-amyotrophic-lateral-sclerosis-9781119745495","title":"Spectrums of Amyotrophic Lateral Sclerosis","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003eSPECTRUMS OF AMYOTROPHIC LATERAL SCLEROSIS Discover state-of-the-art research findings on ALS from leading authors and editors in the fieldIn Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis \u0026amp; Therapeutic Directions, distinguished researchers and editors Dr. Christopher A. Shaw and Jessica R. Morrice deliver a practical and powerful perspective on Amyotrophic Lateral Sclerosis (ALS) as a heterogeneous spectrum of disorders. This increasingly accepted point-of-view allows researchers and medical professionals to develop better targeted interventions and more precise therapies.   In the book, readers will find chapters on a wide variety of critical issues facing ALS researchers and healthcare practitioners treating ALS sufferers, including animal models of ALS, neuronal support cells known to have a pivotal role in ALS, and current challenges in ALS clinical trials, among others. The authors describe pathologic features common to all cases of ALS and why animal models, though crucial, should be interpreted with caution. Finally, multiple genetic and environmental etiologies of the disease are discussed.   Readers will also benefit from the inclusion of:A thorough introduction to ALS as a spectrum disease and the implications for models, therapeutic development and clinical trial designExplorations of the genetic basis of ALS, prospective sALS etiologies, and the involvement of microbiome in ALSDiscussions of ALS-PDC and environmental risk factors, protein aggregation in ALS, defects in RNA metabolism in ALS, and the non-cell autonomous nature of ALS and the involvement of glial cellsExaminations of animal models of ALS and perspectives on previously failed ALS therapeutics and current therapeutic strategiesPerfect for clinical neurologists, healthcare providers and caretakers, clinicians, and researchers studying motor neuron disease, Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis \u0026amp; Therapeutic Directions is also an indispensable resource for the neurodegenerative research community, neurology residents, and graduate-level neuroscience students.\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eContributors xiii\u003c\/p\u003e \u003cp\u003ePreface xvii\u003c\/p\u003e \u003cp\u003eAcknowledgments xix\u003c\/p\u003e \u003cp\u003eForeword xxi\u003c\/p\u003e \u003cp\u003eCHAPTER 1 Clinical Heterogeneity of ALS – Implications for Models and Therapeutic Development 1\u003c\/p\u003e \u003cp\u003eSerena Lattante and Mario Sabatelli\u003c\/p\u003e \u003cp\u003eIntroduction 1\u003c\/p\u003e \u003cp\u003eClinical Heterogeneity of ALS 2\u003c\/p\u003e \u003cp\u003eFamilial and Sporadic ALS 2\u003c\/p\u003e \u003cp\u003eAge of Onset 3\u003c\/p\u003e \u003cp\u003eSurvival 3\u003c\/p\u003e \u003cp\u003eClassic ALS, LMN Form, and UMN Form 4\u003c\/p\u003e \u003cp\u003eSite of Onset 4\u003c\/p\u003e \u003cp\u003eDiagnosis of ALS 5\u003c\/p\u003e \u003cp\u003eALS and Its Relationship with Frontotemporal\u003c\/p\u003e \u003cp\u003eDementia and Myopathies 5\u003c\/p\u003e \u003cp\u003ePleiotropy of ALS Genes 6\u003c\/p\u003e \u003cp\u003eGenetic Models to Study ALS 8\u003c\/p\u003e \u003cp\u003eIn Vivo Models 8\u003c\/p\u003e \u003cp\u003eIn Vitro Models 9\u003c\/p\u003e \u003cp\u003eConclusion 10\u003c\/p\u003e \u003cp\u003eConflict of Interest 11\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 11\u003c\/p\u003e \u003cp\u003eReferences 11\u003c\/p\u003e \u003cp\u003eCHAPTER 2 Genetic Basis of ALS 17\u003c\/p\u003e \u003cp\u003eJay P. Ross, Patrick A. Dion, and Guy A. Rouleau\u003c\/p\u003e \u003cp\u003eIntroduction 17\u003c\/p\u003e \u003cp\u003eGenes Causing ALS 18\u003c\/p\u003e \u003cp\u003eSuperoxide Dismutase 1 (SOD1) 18\u003c\/p\u003e \u003cp\u003eTAR DNA‐Binding Protein 43 (TDP‐43) 19\u003c\/p\u003e \u003cp\u003eFused in Sarcoma (FUS) 19\u003c\/p\u003e \u003cp\u003eChromosome 9 Open Reading Frame 72 (C9orf72) 20\u003c\/p\u003e \u003cp\u003eRecently Discovered Genes 21\u003c\/p\u003e \u003cp\u003eAnnexin A11 (ANXA11) 21\u003c\/p\u003e \u003cp\u003eGlycosyltransferase 8 Domain Containing 1 (GLT8D1) 23\u003c\/p\u003e \u003cp\u003eStathmin‐2 (STMN2) 23\u003c\/p\u003e \u003cp\u003eAspects of ALS Heritability 24\u003c\/p\u003e \u003cp\u003eSporadic vs. Familial 24\u003c\/p\u003e \u003cp\u003ePenetrance and the Oligogenic Hypothesis 24\u003c\/p\u003e \u003cp\u003eMultistep Model 25\u003c\/p\u003e \u003cp\u003eNoncoding Variation 25\u003c\/p\u003e \u003cp\u003eRegulatory and Intronic Variants 25\u003c\/p\u003e \u003cp\u003eEpigenetics 26\u003c\/p\u003e \u003cp\u003eConclusions 27\u003c\/p\u003e \u003cp\u003eAcknowledgments 27\u003c\/p\u003e \u003cp\u003eConflict of Interest 27\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 28\u003c\/p\u003e \u003cp\u003eReferences 28\u003c\/p\u003e \u003cp\u003eCHAPTER 3 Susceptibility Genes and Epigenetics in Sporadic ALS 35\u003c\/p\u003e \u003cp\u003eJessica R. Morrice, Christopher A. Shaw,\u003c\/p\u003e \u003cp\u003eand Cheryl Y. Gregory‐Evans\u003c\/p\u003e \u003cp\u003eIntroduction 35\u003c\/p\u003e \u003cp\u003eEnvironmental Associations in sALS 36\u003c\/p\u003e \u003cp\u003eGenetic Basis of sALS 38\u003c\/p\u003e \u003cp\u003eIdentification of sALS Susceptibility Genes 39\u003c\/p\u003e \u003cp\u003eCandidate sALS Susceptibility Genes 40\u003c\/p\u003e \u003cp\u003eUnc13a 40\u003c\/p\u003e \u003cp\u003eDpp6 40\u003c\/p\u003e \u003cp\u003eC21orf2 41\u003c\/p\u003e \u003cp\u003eEpigenetic Mechanisms in sALS 41\u003c\/p\u003e \u003cp\u003eMethylation in sALS 41\u003c\/p\u003e \u003cp\u003emiRNAs in sALS 42\u003c\/p\u003e \u003cp\u003ePost‐Translational Histone Modification in sALS 43\u003c\/p\u003e \u003cp\u003eEpigenetic Analysis in Monozygotic sALS Twins 44\u003c\/p\u003e \u003cp\u003eModifications to the Epigenome by Environmental Factors 44\u003c\/p\u003e \u003cp\u003eIn Utero Environmental Exposures 45\u003c\/p\u003e \u003cp\u003eEnvironmental in Utero Epigenomic Alterations 45\u003c\/p\u003e \u003cp\u003ePost Utero Exposures 45\u003c\/p\u003e \u003cp\u003eConclusion 46\u003c\/p\u003e \u003cp\u003eConflict of Interest 46\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 47\u003c\/p\u003e \u003cp\u003eReferences 47\u003c\/p\u003e \u003cp\u003eCHAPTER 4 The Lessons of ALS‐PDC – Environmental Factors\u003c\/p\u003e \u003cp\u003ein ALS Etiology 57\u003c\/p\u003e \u003cp\u003eChristopher A. Shaw and Thomas E. Marler\u003c\/p\u003e \u003cp\u003eIntroduction 57\u003c\/p\u003e \u003cp\u003eKoch’s Postulates in the Search of Etiological ALS Factors 58\u003c\/p\u003e \u003cp\u003eNeurological Disease Clusters 59\u003c\/p\u003e \u003cp\u003eThe Natural History of ALS‐PDC 60\u003c\/p\u003e \u003cp\u003eInvestigating Etiological Factors 62\u003c\/p\u003e \u003cp\u003eIdentified Cycad Toxicants 67\u003c\/p\u003e \u003cp\u003eAluminum and Ionic Etiologies for ALS‐PDC 69\u003c\/p\u003e \u003cp\u003eOther Molecules That Might Have Been Involved in ALS‐PDC 70\u003c\/p\u003e \u003cp\u003eA Putative Viral Etiology for ALS‐PDC on Guam\u003c\/p\u003e \u003cp\u003eand ALS in General 70\u003c\/p\u003e \u003cp\u003eThe Continuing Importance of ALS‐PDC 71\u003c\/p\u003e \u003cp\u003eSummary and Conclusions 73\u003c\/p\u003e \u003cp\u003eAcknowledgments 74\u003c\/p\u003e \u003cp\u003eConflict of Interest 74\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 74\u003c\/p\u003e \u003cp\u003eReferences 75\u003c\/p\u003e \u003cp\u003eCHAPTER 5 The Microbiome of ALS – Does It Start from the Gut? 81\u003c\/p\u003e \u003cp\u003eAudrey Labarre and Alex Parker\u003c\/p\u003e \u003cp\u003eIntroduction 81\u003c\/p\u003e \u003cp\u003eRecent Studies 82\u003c\/p\u003e \u003cp\u003eAnimal and in vitro Studies 82\u003c\/p\u003e \u003cp\u003eClinical Studies 91\u003c\/p\u003e \u003cp\u003eHow Could the Microbiome Contribute to ALS? 92\u003c\/p\u003e \u003cp\u003eGut Barrier and Membrane Permeability 93\u003c\/p\u003e \u003cp\u003eInflammation and Immune Response 94\u003c\/p\u003e \u003cp\u003eNeurotoxins 95\u003c\/p\u003e \u003cp\u003eEnergy Metabolism 96\u003c\/p\u003e \u003cp\u003eMicrobiome Modulation as a Potential Therapeutic Avenue 96\u003c\/p\u003e \u003cp\u003eConclusion 97\u003c\/p\u003e \u003cp\u003eConflict of Interest 97\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 97\u003c\/p\u003e \u003cp\u003eReferences 98\u003c\/p\u003e \u003cp\u003eChapter 6 Protein Aggregation in Amyotrophic Lateral Sclerosis 105\u003c\/p\u003e \u003cp\u003eChristen G. Chisholm, Justin J. Yerbury,\u003c\/p\u003e \u003cp\u003eand Luke McAlary\u003c\/p\u003e \u003cp\u003eIntroduction 105\u003c\/p\u003e \u003cp\u003ePathological Protein Inclusions Associated with ALS 106\u003c\/p\u003e \u003cp\u003eProtein Homeostasis and Misfolded Protein\u003c\/p\u003e \u003cp\u003ePartitioning in ALS 107\u003c\/p\u003e \u003cp\u003eConsequences of Protein Aggregation in ALS 108\u003c\/p\u003e \u003cp\u003eThe Primary Aggregating Proteins in ALS 110\u003c\/p\u003e \u003cp\u003eSuperoxide Dismutase‐1 (SOD1) 110\u003c\/p\u003e \u003cp\u003eTransactivated Response DNA Binding\u003c\/p\u003e \u003cp\u003eProtein 43 (TDP‐43) 111\u003c\/p\u003e \u003cp\u003eFused in Sarcoma (FUS) 111\u003c\/p\u003e \u003cp\u003ePrion‐like Propagation of Protein Aggregation in ALS 112\u003c\/p\u003e \u003cp\u003eConclusion 113\u003c\/p\u003e \u003cp\u003eAcknowledgments 114\u003c\/p\u003e \u003cp\u003eConflict of Interest 114\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 114\u003c\/p\u003e \u003cp\u003eReferences 114\u003c\/p\u003e \u003cp\u003eCHAPTER 7 Evidence for a Growing Involvement of Glia\u003c\/p\u003e \u003cp\u003ein Amyotrophic Lateral Sclerosis 123\u003c\/p\u003e \u003cp\u003eRowan A. W. Radford, Andres Vidal‐Itriago,\u003c\/p\u003e \u003cp\u003eNatalie M. Scherer, Albert Lee, Manuel Graeber,\u003c\/p\u003e \u003cp\u003eRoger S. Chung, and Marco Morsch\u003c\/p\u003e \u003cp\u003eIntroduction 123\u003c\/p\u003e \u003cp\u003eNon‐neuronal Cells Play Important Roles\u003c\/p\u003e \u003cp\u003ein Neurodegeneration Including in ALS 123\u003c\/p\u003e \u003cp\u003eGlial Cells and Their Established Functions 123\u003c\/p\u003e \u003cp\u003eNeurodegeneration and the Role of Glial Cells 124\u003c\/p\u003e \u003cp\u003eGlia in ALS 124\u003c\/p\u003e \u003cp\u003eGlial Dysfunction Is a Common Hallmark\u003c\/p\u003e \u003cp\u003eof ALS Patients 125\u003c\/p\u003e \u003cp\u003eGlial Activation in ALS Models 126\u003c\/p\u003e \u003cp\u003eMajor Pathological Forms of ALS 126\u003c\/p\u003e \u003cp\u003eMicroglia‐Related ALS Pathology 126\u003c\/p\u003e \u003cp\u003eMicroglia in SOD1‐ALS Pathology 126\u003c\/p\u003e \u003cp\u003eMicroglia in TDP‐43‐ALS Pathology 127\u003c\/p\u003e \u003cp\u003eMicroglia in FUS‐ALS Pathology 128\u003c\/p\u003e \u003cp\u003eAstrocyte‐Related ALS Pathology 128\u003c\/p\u003e \u003cp\u003eOligodendrocyte‐Related ALS Pathology\u003c\/p\u003e \u003cp\u003eand Glial Inclusion Formation 129\u003c\/p\u003e \u003cp\u003eGlial Inclusion Formation in ALS 130\u003c\/p\u003e \u003cp\u003eOligodendrocytes 130\u003c\/p\u003e \u003cp\u003eAstrocytes 131\u003c\/p\u003e \u003cp\u003eThe Role of Glial Cells in SOD1 Pathology Might Be\u003c\/p\u003e \u003cp\u003eDifferent from Other Forms of ALS 131\u003c\/p\u003e \u003cp\u003eConclusion 132\u003c\/p\u003e \u003cp\u003eAcknowledgments 134\u003c\/p\u003e \u003cp\u003eConflict of Interest 134\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 134\u003c\/p\u003e \u003cp\u003eReferences 134\u003c\/p\u003e \u003cp\u003eCHAPTER 8 Animal Models of ALS – Current and Future\u003c\/p\u003e \u003cp\u003ePerspectives 143\u003c\/p\u003e \u003cp\u003eRobert A. Déziel, Amber L. Marriott, Denis G. Kay,\u003c\/p\u003e \u003cp\u003eand Daphne A. Gill\u003c\/p\u003e \u003cp\u003eIntroduction 143\u003c\/p\u003e \u003cp\u003eThe Clinical Manifestations of ALS 143\u003c\/p\u003e \u003cp\u003eLimb Onset 144\u003c\/p\u003e \u003cp\u003eBulbar Onset 144\u003c\/p\u003e \u003cp\u003eRespiratory Onset 144\u003c\/p\u003e \u003cp\u003eCurrent and Experimental Pharmacological Interventions 145\u003c\/p\u003e \u003cp\u003eRiluzole 145\u003c\/p\u003e \u003cp\u003eEdaravone 146\u003c\/p\u003e \u003cp\u003eFuture Directions for Pharmacological Interventions 146\u003c\/p\u003e \u003cp\u003eCausative Factors in the Development of ALS 146\u003c\/p\u003e \u003cp\u003eGenetic Factors 146\u003c\/p\u003e \u003cp\u003eEnvironmental and Epigenetic Factors 148\u003c\/p\u003e \u003cp\u003eGut and Microbial Factors 148\u003c\/p\u003e \u003cp\u003eAnimal Models of ALS 150\u003c\/p\u003e \u003cp\u003eOne‐hit Models of ALS 150\u003c\/p\u003e \u003cp\u003eMulti‐hit Models of ALS 151\u003c\/p\u003e \u003cp\u003eFuture Model Development 153\u003c\/p\u003e \u003cp\u003eAcknowledgments 153\u003c\/p\u003e \u003cp\u003eConflict of Interest 154\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 154\u003c\/p\u003e \u003cp\u003eReferences 154\u003c\/p\u003e \u003cp\u003eCHAPTER 9 Clinical Trials in ALS – Current Challenges\u003c\/p\u003e \u003cp\u003eand Strategies for Future Directions 161\u003c\/p\u003e \u003cp\u003eKristiana Salmon and Angela Genge 161\u003c\/p\u003e \u003cp\u003eIntroduction 161\u003c\/p\u003e \u003cp\u003eChallenges in ALS Clinical Trials 162\u003c\/p\u003e \u003cp\u003eDisease Heterogeneity 162\u003c\/p\u003e \u003cp\u003eLack of Established Biomarkers 163\u003c\/p\u003e \u003cp\u003eLimitations of Conventional Outcome Measures 163\u003c\/p\u003e \u003cp\u003eALSFRS‐R 163\u003c\/p\u003e \u003cp\u003eFVC\/SVC 164\u003c\/p\u003e \u003cp\u003eHHD 164\u003c\/p\u003e \u003cp\u003eSurvival vs. Function 164\u003c\/p\u003e \u003cp\u003ePhase II Trial “Paradox” 165\u003c\/p\u003e \u003cp\u003ePatient Recruitment and Retention 166\u003c\/p\u003e \u003cp\u003eAssumptions for Lead‐In Phases 166\u003c\/p\u003e \u003cp\u003eNavigating Regulatory Nuances 167\u003c\/p\u003e \u003cp\u003eFuture Directions 167\u003c\/p\u003e \u003cp\u003eAdvances in Disease Understanding and Assessment 168\u003c\/p\u003e \u003cp\u003eDisease Heterogeneity 168\u003c\/p\u003e \u003cp\u003eEmerging Biomarkers 168\u003c\/p\u003e \u003cp\u003eNovel Outcome Measures 169\u003c\/p\u003e \u003cp\u003eNew Approaches to Trial Design 170\u003c\/p\u003e \u003cp\u003eCautious Phase II Design 170\u003c\/p\u003e \u003cp\u003eAdaptive Trial Design 171\u003c\/p\u003e \u003cp\u003ePlatform Trials 172\u003c\/p\u003e \u003cp\u003eBayesian Statistics 172\u003c\/p\u003e \u003cp\u003eEducation 173\u003c\/p\u003e \u003cp\u003ePeople Make or Break a Trial 173\u003c\/p\u003e \u003cp\u003eConclusion 174\u003c\/p\u003e \u003cp\u003eAcknowledgments 175\u003c\/p\u003e \u003cp\u003eConflict of Interest 175\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 175\u003c\/p\u003e \u003cp\u003eReferences 175\u003c\/p\u003e \u003cp\u003eCHAPTER 10 Future Priorities and Directions in ALS Research and Treatment 181\u003c\/p\u003e \u003cp\u003eJessica R. Morrice, Michael Kuo,\u003c\/p\u003e \u003cp\u003eand Christopher A. Shaw\u003c\/p\u003e \u003cp\u003eIntroduction 181\u003c\/p\u003e \u003cp\u003eEtiological Heterogeneity of ALS 182\u003c\/p\u003e \u003cp\u003eALS Risk Factors 183\u003c\/p\u003e \u003cp\u003eCellular Dysfunction in ALS 185\u003c\/p\u003e \u003cp\u003eALS as a “Treatable” Disease 186\u003c\/p\u003e \u003cp\u003eThe Importance of Effective Biomarkers 187\u003c\/p\u003e \u003cp\u003eFuture Therapeutic Avenues for a Heterogeneous Disease 188\u003c\/p\u003e \u003cp\u003eOngoing Clinical Trials Using CuATSM 188\u003c\/p\u003e \u003cp\u003eConclusions and the Road Forward in ALS Research and Treatment 190\u003c\/p\u003e \u003cp\u003eConflict of Interest 191\u003c\/p\u003e \u003cp\u003eCopyright and Permission Statement 191\u003c\/p\u003e \u003cp\u003eReferences 191\u003c\/p\u003e \u003cp\u003eIndex 000\u003c\/p\u003e","brand":"John Wiley and Sons Ltd","offers":[{"title":"Default Title","offer_id":49407135678807,"sku":"9781119745495","price":95.36,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119745495.jpg?v=1730498305","url":"https:\/\/bookcurl.com\/products\/spectrums-of-amyotrophic-lateral-sclerosis-9781119745495","provider":"Book Curl","version":"1.0","type":"link"}