Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses
| Autor: | David Leppert, Olga Ciccarelli, Maria Pia Sormani, Claudia A. M. Wheeler-Kingshott, Davorka Tomic, Elisabetta Verdun di Cantogno, David Baker, Gavin Giovannoni, David L. Selwood, Robert Hyde, Paul M. Matthews, Klaus Schmierer, Shibeshih Belachew, Daniele Carassiti, Gary Cutter, Robert M. Herndon, Ali-Frederic Ben-Amor, Harold Koendgen, Volker Knappertz |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Multiple Sclerosis Inflammation Degeneration (medical) Primary progressive 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Secondary progressive Progressive multiple sclerosis Axonopathy business.industry Multiple sclerosis General Medicine Multiple Sclerosis Chronic Progressive medicine.disease Length-dependent Axons Asynchronous progressive multiple sclerosis Chronic Progressive 030104 developmental biology Siponimod Neurology chemistry Reserve capacity Neurology (clinical) medicine.symptom Therapeutic lag business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Multiple Sclerosis and Related Disorders. 12:70-78 |
| ISSN: | 2211-0348 |
| Popis: | Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms. However, anti-inflammatory therapies may modify these damaged pathways, but with a therapeutic lag that may take years to manifest. Based on these observations we propose that clinically apparent neurodegenerative components of progressive MS may occur in a length-dependent manner and asynchronously. If this hypothesis is confirmed it may have major implications for the future design of progressive MS trials. |
| Databáze: | OpenAIRE |
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