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.
1. Cover image - p. i 2. Title page - p. ii 3. Table of Contents - p. iii 4. Series Page - p. iii 5. Copyright - p. iii 6. Handbook of Clinical Neurology 3rd Series - p. iii 7. Foreword - p. ix 8. In Memoriam–Michael Parkinson - p. x 9. Preface - p. xiii 10. Contributors - p. xiv 11. Part 3 - p. xiv 12. Part 3: Basic science development - p. xiv 13. Chapter 1: Role of rodent models in advancing precision medicine for Parkinson's disease - p. 10 14. Chapter 2: The allure and pitfalls of the prion-like aggregation in neurodegeneration - p. 17 15. Chapter 3: The shift to a proteinopenia paradigm in neurodegeneration - p. 23 16. Chapter 4: Disease mechanisms as subtypes: Lysosomal dysfunction in the endolysosomal Parkinson's disease subtype - p. 33 17. Chapter 5: Disease mechanisms as Subtypes: Mitochondrial and bioenergetic dysfunction - p. 53 18. Chapter 6: Disease mechanisms as subtypes: Immune dysfunction in Parkinson's disease - p. 81 19. Chapter 7: Disease mechanisms as subtypes: Inflammation in Parkinson disease and related disorders - p. 95 20. Chapter 8: Disease mechanisms as subtypes: Microbiome - p. 117 21. Chapter 9: LRRK2: Genetic mechanisms vs genetic subtypes - p. 133 22. Chapter 10: Genetic mechanism vs genetic subtypes: The example of GBA - p. 161 23. Chapter 11: Subtyping monogenic disorders: Huntington disease - p. 171 24. Part 4 - p. 184 25. Part 4: Clinical trials and therapeutic approaches - p. 184 26. Chapter 12: Disease-modifying vs symptomatic treatments: Splitting over lumping - p. 190 27. Chapter 13: Restorative cell and gene therapies for Parkinson's disease - p. 211 28. Chapter 14: The promise and challenges of extracellular vesicles in the diagnosis of neurodegenerative diseases - p. 227 29. Chapter 15: Therapeutic potential of extracellular vesicles in neurodegenerative disorders - p. 248 30. Chapter 16: Lessons from antiamyloid-β immunotherapies in Alzheimer's disease - p. 273 31. Chapter 17: Lessons from immunotherapies in multiple sclerosis - p. 293 32. Chapter 18: Adaptive clinical trials and master protocols - p. 313 33. Chapter 19: Role of novel endpoints and evaluations of response in Parkinson disease - p. 328 34. Chapter 20: Leveraging the regulatory framework to facilitate drug development in Parkinson's disease - p. 347 35. Index - p. 359
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.
1. Cover image - p. i 2. Title page - p. ii 3. Table of Contents - p. iii 4. Series Page - p. iii 5. Copyright - p. iii 6. Handbook of Clinical Neurology 3rd Series - p. iii 7. Foreword - p. ix 8. In Memoriam–Michael Parkinson - p. x 9. Preface - p. xiii 10. Contributors - p. xiv 11. Part 3 - p. xiv 12. Part 3: Basic science development - p. xiv 13. Chapter 1: Role of rodent models in advancing precision medicine for Parkinson's disease - p. 10 14. Chapter 2: The allure and pitfalls of the prion-like aggregation in neurodegeneration - p. 17 15. Chapter 3: The shift to a proteinopenia paradigm in neurodegeneration - p. 23 16. Chapter 4: Disease mechanisms as subtypes: Lysosomal dysfunction in the endolysosomal Parkinson's disease subtype - p. 33 17. Chapter 5: Disease mechanisms as Subtypes: Mitochondrial and bioenergetic dysfunction - p. 53 18. Chapter 6: Disease mechanisms as subtypes: Immune dysfunction in Parkinson's disease - p. 81 19. Chapter 7: Disease mechanisms as subtypes: Inflammation in Parkinson disease and related disorders - p. 95 20. Chapter 8: Disease mechanisms as subtypes: Microbiome - p. 117 21. Chapter 9: LRRK2: Genetic mechanisms vs genetic subtypes - p. 133 22. Chapter 10: Genetic mechanism vs genetic subtypes: The example of GBA - p. 161 23. Chapter 11: Subtyping monogenic disorders: Huntington disease - p. 171 24. Part 4 - p. 184 25. Part 4: Clinical trials and therapeutic approaches - p. 184 26. Chapter 12: Disease-modifying vs symptomatic treatments: Splitting over lumping - p. 190 27. Chapter 13: Restorative cell and gene therapies for Parkinson's disease - p. 211 28. Chapter 14: The promise and challenges of extracellular vesicles in the diagnosis of neurodegenerative diseases - p. 227 29. Chapter 15: Therapeutic potential of extracellular vesicles in neurodegenerative disorders - p. 248 30. Chapter 16: Lessons from antiamyloid-β immunotherapies in Alzheimer's disease - p. 273 31. Chapter 17: Lessons from immunotherapies in multiple sclerosis - p. 293 32. Chapter 18: Adaptive clinical trials and master protocols - p. 313 33. Chapter 19: Role of novel endpoints and evaluations of response in Parkinson disease - p. 328 34. Chapter 20: Leveraging the regulatory framework to facilitate drug development in Parkinson's disease - p. 347 35. Index - p. 359
