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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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“through the use of pharmacological disease-modifying therapies (DMTs).(5) Despite the acceptance of DMTs and their effectiveness, pwMS have demonstrated a desire for greater access to self-management programs that use lifestyle modification to manage known risk factors for disease progression.”
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“MS is still an incurable disease, but current disease-modifying therapies (DMTs) prolong MS patients’ quality lifetime with no clinical and radiological disease progression [4].”
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“Magnetic resonance imaging (MRI) and cerebrospinal fluid analysis usually support the diagnosis [24].”
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Morcom, L. R., Xia, W., Xu, Z., Awasthi, Y., Geywitz, C., Ellis, M. O., Noli, T., Zulji, A., Yamamoto, D., Girdler, G. C., et al. (2026) · Nature · doi:10.1038/s41586-026-10310-3 · Cited by 6
“Cortical atrophy, reflecting degeneration of grey-and white-matter compartments, remains a consistent feature of progressive MS despite effective anti-B and anti-T cell immune therapies 10,11 .”
Calvillo-Robledo, A., Ramírez-Farías, C., Valdez‐Urias, F., Huerta-Carreón, E. P., & Quintanar‐Stephano, A. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1138627 · Cited by 6
Gupta, A., Roy, A., Pandit, S., Pandey, N., & Rustagi, S. (2023) · OBM Neurobiology · doi:10.21926/obm.neurobiol.2304186 · Cited by 6
Janakiraman, M., Leliavski, A., Varadarajulu, J., Jenne, D. E., & Krishnamoorthy, G. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02974-9 · Cited by 6
“Also, historically MS was viewed as a T cell-driven disease but the role of B cells and antibodies in the pathogenesis is increasingly being appreciated [33].”
BackgroundNatalizumab promotes anti-inflammatory and repair effects in multiple sclerosis
Lereim, R. R., Nytrová, P., Guldbrandsen, A., Havrdová, E., Myhr, K., Barsnes, H., & Berven, F. S. (2024) · PLoS ONE · doi:10.1371/journal.pone.0300914 · Cited by 7
Sapouna, V., Zikopoulos, A., Thanopoulou, S., Zachariou, D., Giannakis, I., Kaltsas, A., Sopheap, B., Sofikitis, N., & Zachariou, A. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14040355 · Cited by 6
“The origins of MS remain uncertain, but it is commonly regarded as a multifactorial disorder involving a combination of genetic predisposition and environmental factors [2].”
BackgroundModeling and simulation for prediction of multiple sclerosis progression
Prathapan, V., Eipert, P., Wigger, N., Kipp, M., Appali, R., & Schmitt, O. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.108416 · Cited by 6
Ojo, T. O., Elegbeleye, O. E., Bolaji, O. Q., Adelusi, T. I., Oladipo, E. K., Olawuyi, M. O., Afolayan, B. O., Oyaronbi, A. O., Ogunjobi, T. T., Oyewole, M. P., et al. (2024) · Neurogenetics · doi:10.1007/s10048-024-00764-w · Cited by 6
“Currently, the decision to treat MS induced by EBV focuses on management therapy which directs the drugs to MS-associated symptoms rather than the causative agent [41, 42].”
Irastorza-Valera, L., Gómez, E. S., Benítez, J. M., Montáns, F. J., & Saucedo‐Mora, L. (2024) · Biomimetics · doi:10.3390/biomimetics9060362 · Cited by 7
“Treatment strategies have rapidly improved in a palliative sense but continuously fail to remedy continuous neurodegeneration [278].”
BackgroundTNF-alfa Gene Polymorphism Associations with Multiple Sclerosis
Kalvaitis, L., Gedvilaitė, G., Kriaučiūnienė, L., Balnytė, R., & Liutkevičienė, R. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13133693 · Cited by 6
“Other studies suggest that it is a multifactorial disease, meaning that both environmental and genetic factors may play a role in the development of MS [13].”
BackgroundExploring the therapeutic potential of dioscin and diosgenin in neurological disorders
Biswas, S., Patil, P., Ranjan, S., & Gautam, A. (2024) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2024.100069 · Cited by 6
Şenel, P., Faysal, A. A., Ağar, S., Yurtsever, M., & Gölcü, A. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.138083 · Cited by 6
Diffuse nuclear Overhauser effect MRI contrast changes detected in multiple sclerosis subjects at 7T
Jacobs, P. S., Swain, A., Wilson, N. E., Liu, F., Benyard, B., Spangler, B. C., Seitz, M., Fu, A., Nanga, R. P. R., Elliott, M. A., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcaf043 · Cited by 6
Guo, M., Deng, G., Huang, B., Lin, Z., Yang, X., Dong, L., Wang, Z., Guo, Y., Yi, M., Wang, W., et al. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01093 · Cited by 6
Khan, B., Sartaj, R., Rahiyab, M., Ali, S. S., Hussain, Z., Khan, I., & Iqbal, A. (2025) · Human Gene · doi:10.1016/j.humgen.2025.201436 · Cited by 8
Inshasi, J. S. S., Al-Fahad, S. A., Alsaadi, T. M., Hassan, A., Zein, T., Mifsud, V. A., Nouri, S. I., Shakra, M., Shatila, A. O., Szólics, M., et al. (2021) · Neurology and Therapy · doi:10.1007/s40120-021-00243-6 · Cited by 6
“Comprehensive information can be found in regional [8] and international [9–11] guidelines for MS care and from reviews by experts in the field [12, 13].”
Backgroundde Souza, A. M., Pitombeira, M. S., de Souza, L. E., Marques, F. L. N., Buchpiguel, C. A., Real, C. C., & Faria, D. D. P. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.313062 · Cited by 7
“…no treatment (naïve or without treatment for more than 4 months), first-line injectable therapies (beta interferons and glatiramer acetate), oral therapies (fingolimod and dimethyl fumarate), natalizumab, and classic immunosuppressants (azathioprine and methotrexate) (Hauser and Cree, 2020).”
TnP Peptide Suppresses Experimental Autoimmune Encephalomyelitis (EAE) in a Preclinical Mouse Model
Lima, C., Maleski, A. L. A., Bernardo, J. T. G., Zelli, V. C., Komegae, E. N., & Lopes‐Ferreira, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.857692 · Cited by 6
Multiple Sclerosis Treatment in the COVID-19 Era: A Risk-Benefit Approach
Immovilli, P., Morelli, N., Terracciano, C., Rota, E., Marchesi, E., Vollaro, S., Mitri, P. D., Zaino, D., Bazzurri, V., & Guidetti, D. (2022) · Neurology International · doi:10.3390/neurolint14020030 · Cited by 6
Shi, T., Browne, R. W., Tamaño‐Blanco, M., Jakimovski, D., Weinstock‐Guttman, B., Zivadinov, R., Ramanathan, M. K., & Blair, R. H. (2023) · Metabolomics · doi:10.1007/s11306-023-02010-0 · Cited by 6
“Disease modifying therapies aim to alter the course of MS through immune function modifications and increased anti-inflammatory activity (Hauser & Cree, 2020; McGinley et al., 2021).”
BackgroundSánchez‐Bonilla, D., Robles‐Nasta, M., Gallardo‐Pérez, M. M., Hernández-Flores, E. J., Montes-Robles, M. A., Pastelín-Martínez, M. D. L., Garcés‐Eisele, S. J., Olivares‐Gazca, J. C., Ruiz‐Delgado, G. J., & Ruiz-Argüelles, G. J. (2023) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2023.104744 · Cited by 6
Mountford, S., Kahn, M., Balakrishnan, P., Jacyshyn-Owen, E., Eberl, M., Friedrich, B., Joschko, N., & Ziemssen, T. (2023) · Digital Health · doi:10.1177/20552076231173520 · Cited by 6
“Relapses, as well as progression, can both include a variety of clinical presentations including but not limited to fatigue, impaired motor function, spasticity, generalized pain, gait disturbance, speech problems, and cognitive impairment.(9,10) If these symptoms do not partially or fully resolve, but even progress o…”
BackgroundMotavallihaghi, S., Ghaemipanaeian, M., Asl, S. S., Foroughi-Parvar, F., & Maghsood, A. H. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110379 · Cited by 6
Fang, X., Lu, Y., Fu, Y., Liu, Z., Kermode, A. G., Qiu, W., Ling, L., & Liu, C. (2023) · Brain Sciences · doi:10.3390/brainsci13060924 · Cited by 7
“However, with the development of increasingly effective therapies for RRMS, disease-modifying therapies could modify the course of disease through suppression or modulation of immune function [6,7].”
BackgroundGarcía-Ortega, Y. E., Gómez-Gaitán, E. A., Macías-Islas, M. Á., Saldaña-Cruz, A. M., Contreras-Haro, B., Gámez-Nava, J. I., Pérez-Guerrero, E. E., Nava-Valdivia, C. A., Gallardo-Moya, S., Martínez-Hernández, A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914594 · Cited by 6
“These pharmacological treatments modify the course of MS through the suppression or modulation of immune function, preventing the transition of autoreactive T and B lymphocytes across the blood-CSF barrier and through autoreactive lymphocyte depletion [12,13].”
Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis
Kramer, J., Linker, R. A., Paling, D., Czapliński, A., Hoffmann, O. M., Yong, V. W., Barker, N., Ross, A. P., Lucassen, E. B., Gufran, M., et al. (2023) · Multiple Sclerosis Journal - Experimental Translational and Clinical · doi:10.1177/20552173231203816 · Cited by 6
“Advances in the development of DMTs for relapsing forms of MS enabled additional factors, including route and frequency of administration, and requirements for concomitant premedication prior to administration, to be considered when selecting the most appropriate treatment.(1) Two key aspects involved in DMT decisions…”
BackgroundSortino, M., Petrigna, L., Trovato, B., Amato, A., Castorina, A., D’Agata, V., Maugeri, G., & Musumeci, G. (2023) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk8040154 · Cited by 6
“The pharmacological treatment of MS targets acute attacks, reduction in symptoms, and biological activity [8].”
BackgroundSchneider, M., Kramer, J., Banks, A. M., & Moses, H. (2024) · Multiple Sclerosis Journal · doi:10.1177/13524585241242027 · Cited by 6
Toward Functional PET Imaging of the Spinal Cord
Courault, P., Zimmer, L., & Lancelot, S. (2024) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2024.07.002 · Cited by 6
Suppression of experimental autoimmune encephalomyelitis by IgG Fc fragments bearing regRF epitopes
Beduleva, L., Khramova, T., Sidorov, A., Terentiev, A., Николаевна, А. Н., Menshikova, D., Ivanov, P., Fomina, K., Gorbushina, A., Shklyaeva, N., et al. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108309 · Cited by 6
Pleșa, A., Antochi, F. A., Macovei, M.-L., Vîrlan, A.-G., Georgescu, R., Beuran, D.-I., Bucurica, S., Sîrbu, C. A., Axelerad, A. D., & Pleşa, C. (2024) · Diagnostics · doi:10.3390/diagnostics14192198 · Cited by 5
“To assess disease severity, we used the Expanded Disability Status Scale (EDSS), which ranges from 0 to 10 in 0.5 increments based on neurological examination and patient history [17,18].”
MethodInfluentialMakkawi, S., Abulaban, A. A., Malik, Y. M. A., Alshehri, E., Althobaiti, A., Aljarallah, S., Elboghdady, A., AlHajjar, L. M., Shami, S., Bohlega, S., et al. (2025) · Neurology and Therapy · doi:10.1007/s40120-024-00707-5 · Cited by 5
García-Salas, R., Cilleros-Holgado, P., Spirito, A. D., Gómez-Fernández, D., Piñero-Pérez, R., Romero-Domínguez, J. M., Álvarez-Córdoba, M., Reche-López, D., Romero-González, A., López-Cabrera, A., et al. (2025) · Aging · doi:10.18632/aging.206198 · Cited by 8
“Although there are no developed therapeutic agents that can fully cure MS, several medications significantly slow disease progression and alleviate symptoms [8].”
Ciapă, M. A., Donica, V. C., Costea, C. F., & Bogdănici, C. M. (2025) · Diagnostics · doi:10.3390/diagnostics15101189 · Cited by 5
“Despite these advancements, a silent progression independent of relapse was revealed, which had previously been masked by acute episodes and remissions [38].”
Fatigue and its correlation with anxiety and depression in patients with multiple sclerosis in China
Wang, H., Wang, R., Zhao, R., Zhang, G., Zhang, G., & Zhao, X. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1604540 · Cited by 7
Villar-Delfino, P. H., Christo, P. P., & Volpe, C. M. O. (2025) · Sclerosis · doi:10.3390/sclerosis3030028 · Cited by 5
“…MS are initiated and sustained by peripheral immune activation, characterized by the infiltration of autoreactive lymphocytes into the CNS, as well as by resident CNS immune cells, particularly activated microglia, which perpetuate inflammation and contribute to axonal and neuronal damage [18,19].”
Ferrazzano, G., Fantozzi, R., Haggiag, S., Landi, D., Napoli, F., Buscarinu, M. C., Malimpensa, L., Bianco, A. D., Borriello, G., Barbuti, E., et al. (2025) · Neurology and Therapy · doi:10.1007/s40120-025-00818-7 · Cited by 5
Challenges and opportunities in nanotherapeutics targeted for central nervous system disorders
Yong, J. M., Hakobyan, K., Mahmud, S. A. Z., Johnson, D., Lee, J., Diwan, A. D., Gu, Z., Moalem‐Taylor, G., & Mao, G. (2025) · Nanoscale · doi:10.1039/d5nr02463c · Cited by 5
Piedrabuena, M. A., Correale, J. D., Silva, B. A., Fiol, M. P., Marrodán, M., Zárate, M. A., Heriz, A., Ayerbe, J., Míguez, J., Pita, C., et al. (2025) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2025.123727 · Cited by 5
Foong, Y. C., Merlo, D., Gresle, M. M., Buzzard, K. A., Horáková, D., Havrdová, E., Kalinčík, T., Roos, I., Hodgkinson, S. J., Lechner‐Scott, J., et al. (2025) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2025-336513 · Cited by 5
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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