Multiple sclerosis: Immunopathological heterogeneity and its implications

Engelhardt, Britta; Comabella, Manuel; Andrew, Chan

doi:10.1002/eji.202149757

Cited by 10 publications

(6 citation statements)

References 144 publications

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“…Despite significant advancements in targeted therapies for MS, several challenges remain. For example, the development of targeted therapies can be time-consuming and costly, and the efficacy of these therapies may vary depending on disease stage and patient characteristics (22). In addition, the use of targeted therapies may be associated with adverse effects, such as increased risk of infections or malignancies.…”

Section: Targeted Therapies In Multiple Sclerosis: Role Of Precision ...mentioning

confidence: 99%

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

Pathak

2023

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Multiple Sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system. It is a complex and heterogeneous disease, and its pathogenesis is still not completely understood. Precision medicine, which involves the use of advanced technologies such as genomics, proteomics, metabolomics, and imaging to identify specific biomarkers and disease subtypes, is a promising approach to the management of multiple sclerosis. Precision medicine in MS includes the development of targeted therapies that aim to modulate specific immune pathways involved in MS pathogenesis. This review article aims to provide an overview of the current status and future directions of precision medicine in MS. The article discusses the importance of precision diagnostics in MS, including the identification of biomarkers and imaging techniques for MS, as well as the challenges and opportunities of personalized treatment in MS. Targeted therapies in MS are also discussed, including the challenges of developing and implementing these therapies. The article highlights the potential of combination therapies in MS, and the role of AI and ML in improving biomarker identification. The challenges of implementing precision medicine in clinical practice are also addressed, including the standardization of diagnostic criteria and treatment guidelines, and the ethical and legal considerations of personalized treatment. Overall, precision medicine represents a promising approach to the management of MS, with the potential to improve diagnosis, prognosis, and treatment outcomes. However, the implementation of precision medicine in MS clinical practice requires addressing several challenges, including the standardization of diagnostic criteria and treatment guidelines, and the development of affordable and accessible technologies and therapies. With continued research and advances in technology, precision medicine has the potential to transform the field of MS research and clinical practice.

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Section: Targeted Therapies In Multiple Sclerosis: Role Of Precision ...mentioning

confidence: 99%

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

Pathak

2023

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“…Current drug approvals refer to different disease courses and activity. Pathophysiologically multiple sclerosis is currently considered a continuum with acute, focal inflammatory lesions, and spatially compartmentalised chronic inflammation within the CNS; neurodegenerative/neuroregenerative processes may also contribute [4,5]. The extent of the different processes can vary both inter-and intra-individually and over time [5].…”

Section: Commentary On the Different Disease Courses And Activity Of ...mentioning

confidence: 99%

“…Pathophysiologically multiple sclerosis is currently considered a continuum with acute, focal inflammatory lesions, and spatially compartmentalised chronic inflammation within the CNS; neurodegenerative/neuroregenerative processes may also contribute [4,5]. The extent of the different processes can vary both inter-and intra-individually and over time [5]. Thus, from a pathophysiological point of view, the conceptual dichotomy of relapsing vs. progressive is controversial since underlying mechanisms may at least partly overlap.…”

Section: Commentary On the Different Disease Courses And Activity Of ...mentioning

confidence: 99%

Specific Aspects of Immunotherapy for Multiple Sclerosis in Switzerland—A Structured Commentary, Update 2022

Friedli

Salmen

Hoepner

et al. 2022

CTN

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Multiple sclerosis (MS), particularly relapsing MS (RMS), has become a treatable disease in recent decades, and immunotherapies are now able to influence long-term disease course. A wide range of disease-modifying drugs are available, which makes the choice of therapy in individual cases considerably more complex. Due to specific regulatory aspects (partly diverging approvals by Swissmedic compared to the European Medicines Agency (EMA), and an independent evaluation process for the Federal Office of Public Health (FOPH) specialities list (SL)), we issued a consensus recommendation regarding specific aspects of immunotherapy for MS in Switzerland in 2019. Here, we present revised recommendations with an update on newly approved drugs and new safety aspects, also in reference to the risk of COVID-19 infection and vaccination.

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“…This has led to an increasing complexity in the clinical practice in selecting the appropriate DMT for each patient. Patients can present a suboptimal response to a DMT, which results in the appearance of relapses and magnetic resonance imaging (MRI) lesions that lead to the accumulation of disability [4]. Therefore, the identification of biomarkers of clinical response is a major necessity in MS to classify patients as optimal responders to a DMT and avoid the use of ineffective drugs in non-responders.…”

Section: Introductionmentioning

confidence: 99%

Response to Fingolimod in Multiple Sclerosis Patients Is Associated with a Differential Transcriptomic Regulation

Sánchez-Sanz,

Muñoz-Viana,

Sabín-Muñoz

et al. 2024

IJMS

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Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (five responders and five non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signaling pathways. These DEGs were predominantly immune related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). The S1P, NF-kB and TCR signaling pathways were differentially modulated in responder and non-responder patients. These transcriptomic differences offer the potential of being exploited as biomarkers of a clinical response to fingolimod.

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Multiple sclerosis: Immunopathological heterogeneity and its implications

Cited by 10 publications

References 144 publications

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

Specific Aspects of Immunotherapy for Multiple Sclerosis in Switzerland—A Structured Commentary, Update 2022

Response to Fingolimod in Multiple Sclerosis Patients Is Associated with a Differential Transcriptomic Regulation

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