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Treatment of Multiple Sclerosis: A Review
Open accessAbstract
Multiple sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system, and the leading cause of nontraumatic neurological disability in young adults. Effective management requires a multifaceted approach to control acute attacks, manage progressive worsening, and remediate bothersome or disabling symptoms associated with this illness. Remarkable advances in treatment of all forms of MS, and especially for relapsing disease, have favorably changed the long-term outlook for many patients. There also has been a conceptual shift in understanding the immune pathology of MS, away from a purely T-cell-mediated model to recognition that B cells have a key role in pathogenesis. The emergence of higher-efficacy drugs requiring less frequent administration have made these preferred options in terms of tolerability and adherence. Many experts now recommend use of these as first-line treatment for many patients with early disease, before permanent disability is evident.
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“It may also partly explain why immunosuppressive therapies have thus far had little or no effect on disability accumulation in progressive MS trials4.”
From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [4]
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“While disease-modifying therapies have significantly improved prognosis for relapsing forms of multiple sclerosis (RMS), effective treatments for the progressive, neurodegenerative phase are lacking.”
From Insights and challenges on animal models for progressive multiple sclerosis (2026) · cites this paper as [17]
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“Most DMTs are approved for treatment of relapsing MS (RMS) [17], a smaller number have shown benefit in some SPMS populations [19, 22, 23], but only one DMT has shown efficacy for treatment of PPMS, underlining the unmet need of treatment options for these patients [20] (Table 2).”
From Insights and challenges on animal models for progressive multiple sclerosis (2026) · cites this paper as [17]
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“For example, IFN-γ has been proposed to play both stimulatory and suppressive roles in cancer, and type I IFNs are used both as an immunosuppressant to treat multiple sclerosis and as immunostimulatory adjuvant treatments for cancer (for example melanoma) and chronic viral infection (for example HCV)48–50.”
From Causal identification of single-cell experimental perturbation effects with CINEMA-OT (2023) · cites this paper as [50]
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“The development of B-celldepleting anti-CD20 monoclonal antibody (mAb) therapies has led to a better understanding of the role of B and T cells in this disease [2, 3], and, most importantly, has led to a new appreciation of the central role of B cells in MS pathophysiology [4, 5].”
BackgroundSelf-citationBTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair
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“Multiple sclerosis (MS) is the primary cause of neurological disability afflicting young adults, with a worldwide prevalence of more than 2.5 million people [1, 2].”
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“The MS onset is clinically characterized as relapsing–remitting (RRMS), diagnosed in 85 to 90% of patients [1,4].”
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“Multiple sclerosis (MS) is a chronic inflammatory disease that is characterized by demye-lination, neurodegeneration, and gliosis in the CNS. 96 Many researchers have considered MS to be an autoimmune disease in which immune cells infiltrate and attack healthy tissue, causing lesions; however, the…”
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“For MS, highly effective therapies have been developed for limiting disease relapse and focal brain inflammation; however, halting neurodegeneration remains an unmet goal for MS modalities 41 .”
The epidemiology of primary headaches in patients with multiple sclerosis
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“Multiple sclerosis (MS) is a chronic and progressive demyelinating disease of the central nervous system (CNS), which is characterized by spatially and temporally multiple lesions of unknown etiology (Hauser & Cree, 2020).”
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Significance of Mitochondrial Dysfunction in the Progression of Multiple Sclerosis
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Multifaceted Involvement of Microglia in Gray Matter Pathology in Multiple Sclerosis
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“treatments can reduce white matter lesion load but seem rather limited in their ability to significantly reduce or prevent gray matter neurodegeneration.(13)”
BackgroundProlonging the integrated stress response enhances CNS remyelination in an inflammatory environment
Chen, Y., Kunjamma, R. B., Weiner, M., Chan, J. R., & Popko, B. (2021) · eLife · doi:10.7554/elife.65469 · Cited by 42
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“The profound reduction of neuroinflammation in MS by anti-CD20monoclonal antibodies shows that B cells have a critical role in MS pathogenesis [2,54] (Table 1).”
BackgroundSelf-citationHarris, V., Stark, J. W., Williams, A., Roche, M., Malin, M. L., Kumar, A., Carlson, A., Kizilbash, C., Wollowitz, J. S., Andy, C., et al. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03765-6 · Cited by 41
“Most of the currently approved therapies for MS target immune mechanisms and exhibit varying degrees of efficacy in treating active RRMS [7].”
BackgroundMultiple Sclerosis: Therapeutic Strategies on the Horizon
Manjunatha, R. T., Habib, S., Sangaraju, S. L., Yepez, D., & Grandes, X. A. (2022) · Cureus · doi:10.7759/cureus.24895 · Cited by 42
“TABLE 1: Categories of MS RR: Relapsing-remitting, MS: Multiple Sclerosis [1,3] The course of the disease varies among patients [1].”
BackgroundInfluentialRole of Microglial Cells in the Pathophysiology of MS: Synergistic or Antagonistic?
Mado, H., Adamczyk-Sowa, M. H., & Sowa, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031861 · Cited by 43
“This aspect is all the more important because current disease-modifying therapies (DMTs) only reduce the loss of white matter but have limited properties in terms of significant reduction or prevention of gray matter neurodegeneration [5,63].”
Hegen, H., Berek, K., & Deisenhammer, F. (2022) · Wiener Medizinische Wochenschrift · doi:10.1007/s10354-022-00912-7 · Cited by 40
“An ever-increasing number of DMTs have been proven to reduce the number of relapses, accumulation of disability and brain MRI activity [5] and current treatment concepts recognize the importance of early treatment towards suppressing disease activity below the level of detectability [6].”
BackgroundBao, J., Tu, H., Li, Y., Sun, J., Hu, Z., Zhang, F., & Li, J. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.837452 · Cited by 36
“Two hundred million people have been suffering from multiple physical and psychological symptoms caused by MS (Hauser and Cree, 2020).”
BackgroundGrunwald, C., Krętowska-Grunwald, A., Adamska-Patruno, E., Kochanowicz, J., Kułakowska, A., & Chorąży, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052589 · Cited by 39
“A better understanding of the B cell’s role in MS pathophysiology led to the shift from sole T-cell-focused therapies to the introduction of anti-CD20 monoclonal antibodies ocrelizumab and ofatumumab into MS treatment [22].”
BackgroundNeuroprotective effects of rutin against cuprizone-induced multiple sclerosis in mice
Nicola, M. A., Attaai, A., Abdel-Raheem, M. H., Mohammed, A. F., & Abu-Elhassan, Y. F. (2024) · Inflammopharmacology · doi:10.1007/s10787-024-01442-x · Cited by 37
“Patients with MS may become tolerant to these medications or experience serious adverse effects such as progressive multifocal leukoencephalopathy (Hauser and Cree 2020).”
BackgroundZheng, W., Feng, Y., Zeng, Z., Ye, M., Wang, M., Liu, X., Tang, P., Shang, H., Sun, X., Lin, X., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02415-z · Cited by 36
Oertel, F. C., Krämer, J., Motamedi, S., Keihani, A., Zimmermann, H. G., Dimitriou, N. G., Condor-Montes, S., Bereuter, C., Cordano, C., Abdelhak, A., et al. (2023) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000200092 · Cited by 33
“Most approved disease-modifying treatments (DMTs) for MS are targeting the inflammatory disease component with the goal of decelerating or stopping disease progression.(2) Clinical trials, which led to the approval of these DMTs, have used structural outcome parameters both for inflammatory disease activity such as ne…”
BackgroundMethodNOX-induced oxidative stress is a primary trigger of major neurodegenerative disorders
Zilberter, Y., Tabuena, D. R., & Zilberter, M. Y. (2023) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2023.102539 · Cited by 35
“…et al., 2019; Heneka et al., 2014), acquired epilepsy ((Pauletti et al., 2019; Vezzani et al., 2019), ALS (Barbeito et al., 2010; Calvo et al., 2010; Martínez et al., 2020; McCombe and Henderson, 2011; McGeer and McGeer, 2002; Zhao et al., 2013), and MS (Hauser and Cree, 2020; Kamma et al., 2022).”
Shamaeizadeh, N., Varshosaz, J., Mirian, M., & Aliomrani, M. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.01.100 · Cited by 33
Natural Killer Cells in Multiple Sclerosis: Entering the Stage
Beliën, J., Goris, A., & Matthys, P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.869447 · Cited by 35
Gadhave, D. G., Sugandhi, V. V., & Kokare, C. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148674 · Cited by 33
Dexamethasone in Patients with Glioblastoma: A Systematic Review and Meta-Analysis
Scheffler, P., Fung, C., Momjian, S., Koessinger, D., Häni, L., Neidert, N. N., Straehle, J., Volz, F., Schnell, O., Beck, J., et al. (2024) · Cancers · doi:10.3390/cancers16071393 · Cited by 32
“Short-term glucocorticoid administration is generally deemed safe in most patients, even when given in substantial doses, such as in patients with acute worsening of multiple sclerosis [12].”
BackgroundLi, L., Wang, L., & Zhang, L. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c07536 · Cited by 33
Hou, J., Kim, N. H., Cai, T. A., Dahal, K. P., Weiner, H. L., Chitnis, T., Cai, T., & Xia, Z. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.34627 · Cited by 27
Gut Microbiota as a Potential Predictive Biomarker in Relapsing-Remitting Multiple Sclerosis
Navarro‐López, V., Méndez-Miralles, M. Á., Yebra, R. V., Fríes-Ramos, A., Sánchez-Pellicer, P., Ruzafa-Costas, B., Núñez-Delegido, E., Gómez-Gómez, H., Chumillas-Lidón, S., Picó-Monllor, J. A., et al. (2022) · Genes · doi:10.3390/genes13050930 · Cited by 34
“On the other hand, some DMTs (ocrelizumab and ofatumumab) are monoclonal antibodies that bind the CD20 antigen located on the surface of mature B cells and produce their depletion, causing chronic immunosuppression [11].”
BackgroundAiello, A., Coppola, A., Ruggieri, S., Farroni, C., Altera, A. M. G., Salmi, A., Vanini, V., Cuzzi, G., Petrone, L., Meschi, S., et al. (2022) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2022-330175 · Cited by 31
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Şenol, H., Özgün, Ö., Dağ, A., Eken, A., Güner, H., Aykut, G., Topçu, G., & Şen, A. (2023) · Journal of Natural Products · doi:10.1021/acs.jnatprod.2c00798 · Cited by 30
Iron metabolism disorder and multiple sclerosis: a comprehensive analysis
Tang, C. K., Yang, J., Zhu, C., Ding, Y., Yang, S., Xu, B., & He, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1376838 · Cited by 31
“However, current treatments for MS mostly focus on controlling the degree of disease in fl ammation, with limited effectiveness in targeting in fl ammation (6).”
BackgroundBild, W., Vasincu, A., Rusu, R.-N., Ababei, D. C., Stana, B. A., Stanciu, G. D., Savu, B., & Bild, V. (2022) · Biomolecules · doi:10.3390/biom12101429 · Cited by 32
“The initial inflammatory relapsing phase leads to astroglia proliferation [102] and neurodegenerative”
BackgroundReynoso-Moreno, I., Tietz, S., Vallini, E., Engelhardt, B., Gertsch, J., & Chicca, A. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.0c00214 · Cited by 28
Quirant‐Sánchez, B., Mansilla, M. J., Navarro‐Barriuso, J., Presas‐Rodríguez, S., Teniente‐Serra, A., Fondelli, F., Ramo-Tello, C. M., & Martínez-Cáceres, E. M. (2021) · Biomedicines · doi:10.3390/biomedicines9121758 · Cited by 30
Oh, J., Capezzuto, L., Kriara, L., Schjodt‐Eriksen, J., van Beek, J., Bernasconi, C., Montalbán, X., Butzkueven, H., Kappos, L., Giovannoni, G., et al. (2024) · Scientific Reports · doi:10.1038/s41598-023-49299-4 · Cited by 29
“If a participant completed the whole fixed test sequence on weeks 1, 3, and 6, for example, then this participant was considered persistent according to definition (iii) for 3 weeks.”
MethodOnline psychological interventions to improve symptoms in multiple sclerosis: A systematic review
Montañés‐Masias, B., Bort‐Roig, J., Pascual, J. C., Soler, J., & Briones‐Buixassa, L. (2022) · Acta Neurologica Scandinavica · doi:10.1111/ane.13709 · Cited by 27
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“Both clinical forms of MS appear to reflect the same underlying disease process characterized by neuro-inflammation and subsequent neurodegeneration [105, 106] present in all MS lesions across the entire disease course [105–110].”
BackgroundSleep and cognitive outcomes in multiple sclerosis; a systematic review
Golabi, B., Razmaray, H., Sahebari, S. S., Bandehagh, H., Hakimzadeh, Z., Khosroshahi, A., Moghaddamziabari, S., Aghaei, N., Sanaie, S., Talebi, M., et al. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-06103-5 · Cited by 29
“…pharmacological and non-pharmacological strategies for the management of MS symptoms [5–8], as well as effectual disease-modifying therapies [9–11], and supplementations [12, 13] are widely researched and found to be influential in enhancing patients’ quality of life and survival [14, 15].”
BackgroundExtracellular vesicles as drug and gene delivery vehicles in central nervous system diseases
Shi, X., He, W., Gupta, A. B., To, K., Clark, L., Mirle, N., Wynn, T., Wang, D., Ganesh, A., Zeng, H. M., et al. (2025) · Biomaterials Science · doi:10.1039/d4bm01394h · Cited by 31
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Impact of Vitamin D Supplementation on Multiple Sclerosis
Gandhi, F. R., Jhaveri, S., Avanthika, C., Singh, A., Jain, N., Gulraiz, A., Shah, P., & Nasir, F. (2021) · Cureus · doi:10.7759/cureus.18487 · Cited by 29
“Glatiramer acetate is a medication that can be taken continuously throughout pregnancy [59].”
BackgroundHecker, M., Frahm, N., Bachmann, P., Debus, J. L., Haker, M.-C., Mashhadiakbar, P., Langhorst, S. E., Baldt, J., Streckenbach, B., Heidler, F., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.946351 · Cited by 29
“DMDs can prevent the development of new lesions in the brain and spinal cord, reduce the frequency of relapses and delay the progression of disability (Rommer et al., 2019b; Hauser and Cree, 2020; Rommer and Zettl, 2022).”
BackgroundRole of fenofibrate in multiple sclerosis
Abulaban, A. A., Al-Kuraishy, H. M., Al-Gareeb, A. I., Elekhnawy, E., Alanazi, A., Alexiou, A. T., Papadakis, M., & Batiha, G. E. (2024) · European journal of medical research · doi:10.1186/s40001-024-01700-2 · Cited by 26
“One of the mechanisms hypothesized to explain the diffuse neurodegeneration found in MS patients involves mitochondrial dysfunction [40–43].”
BackgroundCordano, C., Werneburg, S., Abdelhak, A., Bennett, D. J., Beaudry‐Richard, A., Duncan, G. J., Oertel, F. C., Boscardin, W. J., Yiu, H., Jabassini, N., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101490 · Cited by 26
Self-citation
Metadata
- Authors
- Hauser, S. L., & Cree, B. A. C.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Hauser, Stephen L.
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 133
- Issue
- 12
- Pages
- 1380-1390.e2
- ISSN
- 0002-9343 (ISSN-L)
- PMC
- PMC7704606
- OpenAlex
- W3042308502
- Cited by
- 969
- References
- 81
- Citations by year
- 2026: 149 · 2025: 208 · 2024: 229 · 2023: 175 · 2022: 135 · 2021: 64 · 2020: 7
- FWCI
- 14.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Novartis
- Roche
- National Institute of Neurological Disorders and Stroke (R35NS111644)
- TG Therapeutics
- Valhalla Foundation
- National Multiple Sclerosis Society (RR 2005-A-13)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- multiple sclerosis, relapsing-remitting multiple sclerosis, disease-modifying therapy, B-cell therapy, T cell-mediated autoimmunity, neurodegeneration, disability progression, symptom management, first-line therapy, long-term prognosis
- MeSH terms
- Antibodies, Monoclonal, Humans, Immunosuppressive Agents, Multiple Sclerosis, Physical Therapy Modalities
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