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The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy

Multiple sclerosis (MS) is a highly heterogeneous disease involving a combination of inflammation, demyelination, and CNS injury. It is the leading cause of non-traumatic neurological disability in younger people. There is no cure, but treatments in the form of immunomodulatory drugs (IMDs) are avai...

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Autor principal: Pachner, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495360/
https://www.ncbi.nlm.nih.gov/pubmed/36140203
http://dx.doi.org/10.3390/biomedicines10092099
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author Pachner, Andrew
author_facet Pachner, Andrew
author_sort Pachner, Andrew
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description Multiple sclerosis (MS) is a highly heterogeneous disease involving a combination of inflammation, demyelination, and CNS injury. It is the leading cause of non-traumatic neurological disability in younger people. There is no cure, but treatments in the form of immunomodulatory drugs (IMDs) are available. Experience over the last 30 years has shown that IMDs, also sometimes called disease-modifying therapies, are effective in downregulating neuroinflammatory activity. However, there are a number of negatives in IMD therapy, including potential for significant side-effects and adverse events, uncertainty about long-term benefits regarding disability outcomes, and very high and increasing financial costs. The two dozen currently available FDA-approved IMDs also are heterogeneous with respect to efficacy and safety, especially long-term safety, and determining an IMD treatment strategy is therefore challenging for the clinician. Decisions about optimal therapy have been particularly difficult in early MS, at the time of the initial clinical demyelinating event (ICDE), at a time when early, aggressive treatment would best be initiated on patients destined to have a highly inflammatory course. However, given the fact that the majority of ICDE patients have a more benign course, aggressive immunosuppression, with its attendant risks, should not be administered to this group, and should only be reserved for patients with a more neuroinflammatory course, a decision that can only be made in retrospect, months to years after the ICDE. This quandary of moderate vs. aggressive therapy facing clinicians would best be resolved by the use of biomarkers that are predictive of future neuroinflammation. Unfortunately, biomarkers, especially molecular biomarkers, have not thus far been particularly useful in assisting clinicians in predicting the likelihood of future neuroinflammation, and thus guiding therapy. However, the last decade has seen the emergence of two highly promising molecular biomarkers to guide therapy in early MS: the CXCL13 index and neurofilament light. This paper will review the immunological and neuroscientific underpinnings of these biomarkers and the data supporting their use in early MS and will propose how they will likely be used to maximize benefit and minimize risk of IMDs in MS patients.
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spelling pubmed-94953602022-09-23 The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy Pachner, Andrew Biomedicines Review Multiple sclerosis (MS) is a highly heterogeneous disease involving a combination of inflammation, demyelination, and CNS injury. It is the leading cause of non-traumatic neurological disability in younger people. There is no cure, but treatments in the form of immunomodulatory drugs (IMDs) are available. Experience over the last 30 years has shown that IMDs, also sometimes called disease-modifying therapies, are effective in downregulating neuroinflammatory activity. However, there are a number of negatives in IMD therapy, including potential for significant side-effects and adverse events, uncertainty about long-term benefits regarding disability outcomes, and very high and increasing financial costs. The two dozen currently available FDA-approved IMDs also are heterogeneous with respect to efficacy and safety, especially long-term safety, and determining an IMD treatment strategy is therefore challenging for the clinician. Decisions about optimal therapy have been particularly difficult in early MS, at the time of the initial clinical demyelinating event (ICDE), at a time when early, aggressive treatment would best be initiated on patients destined to have a highly inflammatory course. However, given the fact that the majority of ICDE patients have a more benign course, aggressive immunosuppression, with its attendant risks, should not be administered to this group, and should only be reserved for patients with a more neuroinflammatory course, a decision that can only be made in retrospect, months to years after the ICDE. This quandary of moderate vs. aggressive therapy facing clinicians would best be resolved by the use of biomarkers that are predictive of future neuroinflammation. Unfortunately, biomarkers, especially molecular biomarkers, have not thus far been particularly useful in assisting clinicians in predicting the likelihood of future neuroinflammation, and thus guiding therapy. However, the last decade has seen the emergence of two highly promising molecular biomarkers to guide therapy in early MS: the CXCL13 index and neurofilament light. This paper will review the immunological and neuroscientific underpinnings of these biomarkers and the data supporting their use in early MS and will propose how they will likely be used to maximize benefit and minimize risk of IMDs in MS patients. MDPI 2022-08-28 /pmc/articles/PMC9495360/ /pubmed/36140203 http://dx.doi.org/10.3390/biomedicines10092099 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Pachner, Andrew
The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy
title The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy
title_full The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy
title_fullStr The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy
title_full_unstemmed The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy
title_short The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy
title_sort brave new world of early treatment of multiple sclerosis: using the molecular biomarkers cxcl13 and neurofilament light to optimize immunotherapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495360/
https://www.ncbi.nlm.nih.gov/pubmed/36140203
http://dx.doi.org/10.3390/biomedicines10092099
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