دورية أكاديمية
Disease-modifying vs symptomatic treatments: Splitting over lumping.
| العنوان: | Disease-modifying vs symptomatic treatments: Splitting over lumping. |
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| المؤلفون: | Duque KR; James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United States., Vizcarra JA; Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States., Hill EJ; James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United States., Espay AJ; James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United States. Electronic address: alberto.espay@uc.edu. |
| المصدر: | Handbook of clinical neurology [Handb Clin Neurol] 2023; Vol. 193, pp. 187-209. |
| نوع المنشور: | Review; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0166161 Publication Model: Print Cited Medium: Internet ISSN: 0072-9752 (Print) Linking ISSN: 00729752 NLM ISO Abbreviation: Handb Clin Neurol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <1985- >: Amsterdam ; New York : Elsevier Original Publication: Amsterdam [Netherlands] : New York : North-Holland Pub. Co. ; Wiley Interscience Division - John Wiley & Sons, [©1969- |
| مواضيع طبية MeSH: | Parkinson Disease*/genetics , Alzheimer Disease*/therapy, Humans ; Biomarkers ; Aging |
| مستخلص: | Clinical trials of putative disease-modifying therapies in neurodegeneration have obeyed the century-old principle of convergence, or lumping, whereby any feature of a clinicopathologic disease entity is considered relevant to most of those affected. While this convergent approach has resulted in important successes in trials of symptomatic therapies, largely aimed at correcting common neurotransmitter deficiencies (e.g., cholinergic deficiency in Alzheimer's disease or dopaminergic deficiency in Parkinson's disease), it has been consistently futile in trials of neuroprotective or disease-modifying interventions. As individuals affected by the same neurodegenerative disorder do not share the same biological drivers, splitting such disease into small molecular/biological subtypes, to match people to therapies most likely to benefit them, is vital in the pursuit of disease modification. We here discuss three paths toward the splitting needed for future successes in precision medicine: (1) encourage the development of aging cohorts agnostic to phenotype in order to enact a biology-to-phenotype direction of biomarker development and validate divergence biomarkers (present in some, absent in most); (2) demand bioassay-based recruitment of subjects into disease-modifying trials of putative neuroprotective interventions in order to match the right therapies to the right recipients; and (3) evaluate promising epidemiologic leads of presumed pathogenetic potential using Mendelian randomization studies before designing the corresponding clinical trials. The reconfiguration of disease-modifying efforts for patients with neurodegenerative disorders will require a paradigm shift from lumping to splitting and from proteinopathy to proteinopenia. (Copyright © 2023 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Alzheimer's disease; Clinical trials; Disease modification; Parkinson's disease; Precision medicine |
| المشرفين على المادة: | 0 (Biomarkers) |
| تواريخ الأحداث: | Date Created: 20230221 Date Completed: 20230223 Latest Revision: 20230223 |
| رمز التحديث: | 20230223 |
| DOI: | 10.1016/B978-0-323-85555-6.00020-5 |
| PMID: | 36803811 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0072-9752 |
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| DOI: | 10.1016/B978-0-323-85555-6.00020-5 |