Precision Medicine in Neurodegenerative Disorders - Part II, Volume 193 - Handbook of Clinical Neurology (July 19, 2023)_(0323855555)_(Elsevier).pdf

Precision Medicine in Neurodegenerative Disorders, Part Two, Volume 194 discusses a major transformation fueled by the recognition that what has worked for developing symptomatic therapies doesn't necessarily work for developing disease modifying therapies. The former depends on addressing convergent, common denominators of disease, present in most of those affected. The latter on divergent biological signals, present in some but absent in most. This work encompasses two volumes separated into multiple sections, including conceptual frameworks, pitfalls in definitions, cohorts, and measures of progression, basic science development, and clinical trials and therapeutic approaches. Precision Medicine in Neurodegenerative Disorders, Part Two, Volume 193 in the Handbook of Clinical Neurology deals with the'How'in the reconfiguration of our approach to slow accelerated brain aging. The book rethinks animal models on which therapies are tested, outlines the progress and expected changes in biological subtyping efforts using lysosomal, endosomal, mitochondrial, immune dysregulation, and inflammatory mechanisms of disease pathophysiology, and the growing role of microbiome in shaping disease. The volume separates the potentially disease-modifying neurorescue and neurorestoration, (e.g., gene therapy and cell replacement therapy) from true precision'medicine'–matching biology with the mechanism of intervention of interest. Specific chapters are dedicated to the promise and challenges of extracellular vesicles for both diagnosis and treatment, the growing application of digital measures and other evaluations of clinical response, the nuts and bolts of novel adaptive clinical trial designs, and the regulatory changes needed to facilitate drug development for disease-modification purposes. Summarizes theory and research on precision medicine in neurodegenerative disorders Covers basic biology, clinical trials and therapeutics Includes disease mechanisms, genetic subtypes, and more Cover Series Page Copyright Copyright Handbook of Clinical Neurology 3rd Series Available titles Foreword Foreword In Memoriam Michael Parkinson In Memoriam–Michael Parkinson Preface Preface Contributors Contributors Role of rodent models in advancing precision medicine for Parkinson ́s disease Introduction Challenges to Subgrouping in PD Rationale for Modeling PD in Rodents Genetic Models of Parkinson's Disease A53T aSyn mice Thy1-aSyn mice (a.k.a. Line 61) GBA1 LRRK2 PINK1 Inducible α-Synuclein Overexpressing Models Viral Vector-Induced Alpha-Synuclein Overexpression Alpha-Synuclein Preformed Fibril Neurotoxin Models of Parkinson's Disease Conclusion References The allure and pitfalls of the prion-like aggregation in neurodegeneration Introduction Origins of the Idea of Prions Extending the Thermodynamic Hypothesis to Protein Unfolding Thermodynamic Hypothesis vs the Prion Hypothesis for Amyloid Aggregation Is the Prion Hypothesis the Luminiferous Ether of Biology? Conclusions