2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Updates and advances in multiple sclerosis neurotherapeutics

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The multiple sclerosis (MS) neurotherapeutic landscape is rapidly evolving. New disease-modifying therapies (DMTs) with improved efficacy and safety, in addition to an expanding pipeline of agents with novel mechanisms, provide more options for patients with MS. While treatment of MS neuroinflammation is well tailored in the existing DMT armamentarium, concerted efforts are currently underway for identifying neuropathological targets and drug discovery for progressive MS. There is also ongoing research to develop agents for remyelination and neuroprotection. Further insights are needed to guide DMT initiation and sequencing as well as to determine the role of autologous stem cell transplantation in relapsing and progressive MS. This review provides a summary of these updates.

          Plain language summary

          The range of treatment options available for multiple sclerosis (MS) is growing, with the aim of developing safer and more effective therapies. There are ongoing efforts to discover additional mechanisms of MS and create drugs that can target these pathways. A more tailored approach will allow better personalization of drug selection for patients. There is currently a special focus on identifying treatment targets for progressive MS, where there are only a limited number of therapeutic options available to date. In addition, there is ongoing research aimed at developing stem cell therapies, drugs that provide neuroprotection and agents that can potentially reverse the damage caused by MS through remyelination. In this review, these topics are summarized.

          Related collections

          Most cited references176

          • Record: found
          • Abstract: found
          • Article: found

          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.

            Adaptive immunity depends on T-cell exit from the thymus and T and B cells travelling between secondary lymphoid organs to survey for antigens. After activation in lymphoid organs, T cells must again return to circulation to reach sites of infection; however, the mechanisms regulating lymphoid organ exit are unknown. An immunosuppressant drug, FTY720, inhibits lymphocyte emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate (S1P) receptors. However, the role of S1P receptors in normal immune cell trafficking is unclear. Here we show that in mice whose haematopoietic cells lack a single S1P receptor (S1P1; also known as Edg1) there are no T cells in the periphery because mature T cells are unable to exit the thymus. Although B cells are present in peripheral lymphoid organs, they are severely deficient in blood and lymph. Adoptive cell transfer experiments establish an intrinsic requirement for S1P1 in T and B cells for lymphoid organ egress. Furthermore, S1P1-dependent chemotactic responsiveness is strongly upregulated in T-cell development before exit from the thymus, whereas S1P1 is downregulated during peripheral lymphocyte activation, and this is associated with retention in lymphoid organs. We find that FTY720 treatment downregulates S1P1, creating a temporary pharmacological S1P1-null state in lymphocytes, providing an explanation for the mechanism of FTY720-induced lymphocyte sequestration. These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              Defining the clinical course of multiple sclerosis

              Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
                Bookmark

                Author and article information

                Journal
                Neurodegener Dis Manag
                Neurodegener Dis Manag
                NMT
                Neurodegenerative Disease Management
                Future Medicine Ltd (London, UK )
                1758-2024
                1758-2032
                31 October 2022
                February 2023
                31 October 2022
                : 13
                : 1
                : 47-70
                Affiliations
                [1 ]Cleveland Clinic, Department of Neurology, Cleveland, OH 44195, USA
                [2 ]Cleveland Clinic, Lou Ruvo Center for Brain Health, Las Vegas, NV 89106, USA
                Author notes
                [* ]Author for correspondence: hershc@ 123456ccf.org
                Author information
                https://orcid.org/0000-0002-5716-5645
                Article
                10.2217/nmt-2021-0058
                10072078
                36314777
                d8082f03-1436-455d-b449-a51ece5037b3
                © 2022 Cleveland Clinic

                This work is licensed under the Creative Commons Attribution 4.0 License

                History
                : 25 December 2021
                : 30 September 2022
                : 31 October 2022
                Page count
                Pages: 24
                Categories
                Review

                autologous hematopoietic stem cell transplantation,btk inhibitors,disease-modifying therapy,early highly effective therapy,escalation therapy,multiple sclerosis,neuroprotective agents,progressive multiple sclerosis,relapsing multiple sclerosis,remyelinating therapies

                Comments

                Comment on this article