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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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Citations
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Self-citationThe Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases
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“Furthermore, identifying the appropriate patient populations is an important consideration given that MS is a heterogeneous disease and, therefore, requires differential treatments.(145) Innovative strategies that could be used to tackle these obstacles include: (i) a multiple-target approach with compounds able to si…”
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“To date, there are no treatments to cure MS, but disease progression control and symptom ease can be obtained with several therapeutic strategies (Ben-Zacharia, 2011; Hauser and Cree, 2020).”
BackgroundRepurposing artemisinins as neuroprotective agents: a focus on the PI3k/Akt signalling pathway
Arthur, R., Navik, U., & Kumar, P. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02350-z · Cited by 18
“These drugs include corticosteroids, immunomodulators, immunosuppressants, interferon 1β, and humanized anti-α 4-integrin antibodies (Hauser and Cree 2020; Lassmann 2013; Leray et al.”
BackgroundNeuro-immune crosstalk in depressive symptoms of multiple sclerosis
Wang, C., Zhou, Y., & Feinstein, A. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106005 · Cited by 20
“particularly during the relapsing phase of MS (Hauser and Cree, 2020), to contribute to improving depression symptoms.”
BackgroundProtein biomarkers in multiple sclerosis
Kim, J. (2023) · encephalitis · doi:10.47936/encephalitis.2022.00101 · Cited by 18
Attia, M. S., Ewida, H. A., Hafez, M. A. A., El‐Maraghy, S. A., & El‐Sawalhi, M. M. (2023) · Diagnostics · doi:10.3390/diagnostics13081448 · Cited by 18
The role of exosomes in central nervous system tissue regeneration and repair
Wang, J., & Yang, L. (2023) · Biomedical Materials · doi:10.1088/1748-605x/ace39c · Cited by 19
Cell replacement therapy with stem cells in multiple sclerosis, a systematic review
Christodoulou, M. V., Petkou, E., Atzemoglou, N., Gkorla, E., Karamitrou, A., Simos, Y. V., Bellos, S., Bekiari, C., Kouklis, P. D., Konitsiotis, S., et al. (2023) · Human Cell · doi:10.1007/s13577-023-01006-1 · Cited by 22
“Existing immunomodulatory agents, despite being very efficient in reducing the rate of relapses, do not prevent progressive neurodegenerative processes, nor do they have any regenerative effect, while they may cause significant adverse effects [3].”
BackgroundGold, R., Schmidt, S., Deisenhammer, F., Motte, J., Richter, N., Taipale, K., Salmen, H. C., Bohland, C., & Schirduan, K. (2024) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864241241382 · Cited by 18
Zhang, J., Wu, M., Li, J., Song, W., Lin, X., & Zhu, L. (2024) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2024.105643 · Cited by 18
Cerebral iron accumulation in multiple sclerosis: Pathophysiology and therapeutic implications.
Bjørklund, G., Wallace, D. R., Hangan, T., BUTNARIU, M., Butnariu, M., Gurgas, L., & Peana, M. (2025) · Autoimmunity Reviews · doi:10.1016/j.autrev.2025.103741 · Cited by 21
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“With these observations in mind, a plethora of disease-modifying therapies aimed at dampening the immune system have become available [70].”
Cathepsins in Neurological Diseases
Lewandowski, D., Konieczny, M., Różycka, A., Chrzanowski, K., Owecki, W., Kalinowski, J., Stepura, M., Jagodziński, P. P., & Dorszewska, J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167886 · Cited by 17
“Key risk factors include Epstein–Barr virus infection, vitamin D deficiency, smoking, and genetic predispositions linked to the major histocompatibility complex (HLA) [106,107].”
Ahmad, S., Ali, S., Rehman, D. A. U., Haq, I. U., Liaqat, I., Aftab, M. N., & Shume, T. (2026) · Journal of Medical Microbiology · doi:10.1099/jmm.0.002117 · Cited by 21
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The Role of Diet and Gut Microbiome in Multiple Sclerosis
Jayasinghe, M., Prathiraja, O., Kayani, A. M. A., Jena, R., Caldera, D., Silva, M. S., Singhal, M., & Pierre, J. (2022) · Cureus · doi:10.7759/cureus.28975 · Cited by 18
“With the development of much more effective treatment modalities, the mean time of 19 years for the progression of RRMS to SPMS has been lengthened [7].”
Papukchieva, S., Stratil, A.-S., Kahn, M., Neß, N.-H., Hollnagel-Schmitz, M., Gerencser, V., Rustemeier, J., Eberl, M., Friedrich, B., & Ziemssen, T. (2024) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864241237857 · Cited by 20
Panghal, A., & Flora, S. J. S. (2024) · Discover Nano · doi:10.1186/s11671-024-04135-0 · Cited by 20
“These treatments include immune system-suppressing drugs, physical therapy and lifestyle adaptations like stress management and exercise [6, 7].”
BackgroundMultiple Sclerosis and the Endogenous Opioid System
Dworsky-Fried, Z., Chadwick, C. I., Kerr, B. J., & Taylor, A. M. W. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.741503 · Cited by 17
Zhang, W., Wu, P.-F., Yin, R., Sun, M., Zhang, R., Liao, X., Lin, Y., & Lü, H. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.817067 · Cited by 17
“HSV viruses lurk in the sensory ganglion of the trigeminal nerve, remain exist lifelong, and could invade CNS (Kimberlin et al., 2001).”
BackgroundInfluentialKearns, P. K. A., Martin, S. J., Chang, J. C., Meijboom, R., York, E. N., Chen, Y., Weaver, C., Stenson, A., Hafezi, K., Thomson, S., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-058506 · Cited by 16
Pau, M., Cocco, E. E., Arippa, F., Casu, G., Porta, M., Menascu, S., Achiron, A., & Kalron, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12093222 · Cited by 17
“Currently, there is no cure for MS; hence, various pharmacological and non-pharmacological treatments are essential in assisting with the management of the disease’s symptoms [3,4].”
BackgroundThe role of Microbiota in the Pathogenesis of Alzheimer’s Disease
Sharma, A., & Martins, I. J. (2023) · Acta Scientifci Nutritional Health · doi:10.31080/asnh.2023.07.1272 · Cited by 16
Anti-inflammatory effect of curcumin on neurological disorders: a narrative review
Zhou, B., & Hu, B. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1658115 · Cited by 19
“Although the precise etiology remains elusive, genome-wide association studies have identi fi ed over 200 risk loci, particularly within the major histocompatibility complex region, underscoring the importance of immune dysregulation (Hauser and Cree, 2020).”
Zha, Z., Liu, Y.-J., Liu, S., Zhang, N., Li, J.-L., Qi, F., Jin, L.-Y., Xue, B., Yang, T., Fan, Y., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3800004 · Cited by 15
“Multiple sclerosis (MS) is a heterogeneous neurodegenerative condition [1] that leads to nontraumatic neurological disability as a result of demyelination and axonal injury of the central nervous system (CNS) [2], for which there is still a lack of e ff ective therapies.”
Drug repurposing: Clemastine fumarate and neurodegeneration
Zhu, J., Ma, R., & Li, G. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113904 · Cited by 16
Martinez-Paz, C., García-Cabrera, E., & Vilches‐Arenas, Á. (2023) · Cannabis and Cannabinoid Research · doi:10.1089/can.2022.0254 · Cited by 16
Hecker, M., Frahm, N., & Zettl, U. K. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics16010003 · Cited by 15
“Additionally, we considered all DMDs approved for the treatment of MS by the US Food and Drug Administration and/or the European Medicines Agency as of June 2023 [8,10,49,50] (Table 2).”
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Impact of serum neurofilament light on clinical decisions in a tertiary multiple sclerosis clinic
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“According to the location and severity of lesions, patients with MS often present with a variety of clinical manifestations, including sensory loss or abnormality, optic nerve symptoms, weakness, facial nerve weakness, ataxia, vertigo, pain, fatigue, bladder and bowel problems, and psychological disorders.(3) Long-ter…”
Tredicine, M., Ria, F., Poerio, N., Lucchini, M., Bianco, A. D., Santis, F. D., Valentini, M., Arcangelis, V. D., Rende, M., Stabile, A. M., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121930 · Cited by 17
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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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