B-Cell-Directed Therapies: A New Era in Multiple Sclerosis Treatment DOI Creative Commons
Panagiotis Kanatas, Ioannis Stouras, Leonidas Stefanis

et al.

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, Journal Year: 2022, Volume and Issue: 50(3), P. 355 - 364

Published: May 16, 2022

ABSTRACT: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that often progresses to severe disability. Previous studies have highlighted role T cells in pathophysiology; however, success B-cell-targeted therapies has led an increased interest how B contribute immunopathology. In this review, we summarize evidence B-cell involvement MS mechanisms, starting with pathology and moving on review aspects cell immunobiology potentially relevant MS. We describe current theories critical contributions inflammatory CNS milieu MS, namely (i) production autoantibodies, (ii) antigen presentation, (iii) proinflammatory cytokines (bystander activation), (iv) EBV involvement. second part medications targeted patients their position therapeutic armamentarium based clinical trials real-world data. Covered strategies include targeting surface molecules such as CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) CD19 (inebilizumab), necessary for activation activating factor (BAFF) (belimumab) Bruton’s Tyrosine Kinase (BTK) (evobrutinib). finally discuss use therapeutics pregnancy.

Language: Английский

Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders DOI Creative Commons
Laura Mitrea, Silvia Amalia Nemeş, Katalin Szabo

et al.

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: March 31, 2022

Over the last 10 years, there has been a growing interest in relationship between gut microbiota, brain, and neurologic-associated affections. As multiple preclinical clinical research studies highlight microbiota’s potential to modulate general state of health state, it goes without saying that microbiota plays significant role neurogenesis, mental cognitive development, emotions, behaviors, progression neuropsychiatric illnesses. Gut produces important biologic products that, through gut-brain axis, are directly connected with appearance evolution neurological psychiatric disorders such as depression, anxiety, bipolar disorder, autism, schizophrenia, Parkinson’s disease, Alzheimer’s dementia, sclerosis, epilepsy. This study reviews recent on link microbiome’s shaping development most common Moreover, special attention is paid use probiotic formulations non-invasive therapeutic opportunity for prevention management neuropsychiatric-associated

Language: Английский

Citations

151
Bruton tyrosine kinase inhibitors for multiple sclerosis DOI Open Access
Julia Krämer, Amit Bar‐Or, Timothy J. Turner

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(5), P. 289 - 304

Published: April 13, 2023

Language: Английский

Citations

99
Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic DOI Creative Commons
de Sèze, Élisabeth Maillart, Antoine Guéguen

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 23, 2023

The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, pieces of evidence now support the view that B cells are essential players sclerosis pathogenic processes. High-efficacy disease-modifying therapies target have emerged over past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, lessen disability progression patients with relapsing Rituximab, ocrelizumab, ofatumumab currently used clinical practice, while phase III trials for ublituximab been recently completed. In this review, we compare four anti-CD20 terms their mechanisms action, routes administration, immunological targets, pharmacokinetic properties. A deeper understanding individual properties these molecules relation efficacy safety profiles is critical use practice.

Language: Английский

Citations

69
Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability DOI Creative Commons
Alise Carlson, Moein Amin, Jeffrey A. Cohen

et al.

Drugs, Journal Year: 2024, Volume and Issue: 84(3), P. 285 - 304

Published: March 1, 2024

Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed therapeutic landscape MS through robust efficacy on clinical manifestations MRI lesion activity, currently anti-CD20 mAb therapies for use in a cornerstone highly effective disease-modifying treatment. Ocrelizumab is only with regulatory approval primary progressive MS. There few data regarding relative these therapies, though several trials ongoing. Safety concerns applicable this class therapeutics relate primarily immunogenicity mechanism action, include infusion-related or injection-related reactions, development hypogammaglobulinemia (leading increased infection malignancy risk), decreased vaccine response. Exploration alternative dose/dosing schedules might be an strategy mitigating risks. Future biosimilar medications make more readily available. Although have led significant improvements disease outcomes, CNS-penetrant still needed effectively address compartmentalized inflammation thought play important role disability progression.

Language: Английский

Citations

18
Tolerance in the Age of Immunotherapy DOI
Jeffrey A. Bluestone, Mark S. Anderson

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(12), P. 1156 - 1166

Published: Sept. 16, 2020

The immune system distinguishes between "self" and "nonself" remembers dangerous exposures. Elaborate mechanisms control responses, but in some cases, the response either does not recognize danger or causes unwanted autoinflammation. authors review advances developing durable tolerance.

Language: Английский

Citations

94
Curcumin-based nanotechnology approaches and therapeutics in restoration of autoimmune diseases DOI
Niloufar Rahiman, Yuliya V. Markina, Prashant Kesharwani

et al.

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 348, P. 264 - 286

Published: June 8, 2022

Language: Английский

Citations

40
The beneficial role of autophagy in multiple sclerosis: Yes or No? DOI
Hayder M. Al‐kuraishy, Majid S. Jabir, Ali I. Al‐Gareeb

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 20(2), P. 259 - 274

Published: Sept. 15, 2023

Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS) due to an increase abnormal peripherally auto-reactive T lymphocytes which elicit autoimmunity. The main pathophysiology MS myelin sheath damage by immune cells and defect in generation oligodendrocytes. Macroautophagy/autophagy critical degradation process that eliminates dysfunctional or superfluous cellular components. Autophagy has property double-edged sword it may have both beneficial detrimental effects on neuropathology. Therefore, this review illustrates protective harmful autophagy with regard disease. prevents progression reducing oxidative stress inflammatory disorders. In contrast, over-activated associated neuropathology case use inhibitors alleviate pathogenesis MS. Furthermore, provokes activation different supporting play intricate role functions modulation regulating cell proliferation related demyelination remyelination. enhances remyelination increasing activity oligodendrocytes, astrocytes. However, induces activating microglia cells. conclusion, specific autophagic activators astrocytes, dendritic (DCs), induce against

Language: Английский

Citations

37
Microglial NLRP3 inflammasome activation in multiple sclerosis DOI
Melis Olcum, Bora Tastan, Cagla Kiser

et al.

Advances in protein chemistry and structural biology, Journal Year: 2019, Volume and Issue: unknown, P. 247 - 308

Published: Nov. 26, 2019

Language: Английский

Citations

69
Role of Peripheral Immune Cells-Mediated Inflammation on the Process of Neurodegenerative Diseases DOI Creative Commons
Qiuyu Yang, Guoqing Wang, Feng Zhang

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 15, 2020

Neurodegenerative diseases are characterized by progressive loss of selectively vulnerable neuronal populations, which contrasts with static neurons due to toxic or metabolic disorders. The mechanisms underlying their nature remain unknown. To date, a timely and well-controlled peripheral inflammatory reaction is verified be essential for neurodegenerative remission. influence inflammation on the central nervous system closely related immune cells activation in blood. participated uncontrolled prolonged that drives chronic progression diseases. Thus, dynamic modulation this interrupting vicious cycle might become disease-modifying therapeutic strategy This review focused role pathological

Language: Английский

Citations

52
Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex) DOI Creative Commons
Stanley Cohan, Barry Hendin, Anthony T. Reder

et al.

CNS Drugs, Journal Year: 2021, Volume and Issue: 35(7), P. 743 - 767

Published: July 1, 2021

Recombinant interferon (IFN) β-1b was approved by the US Food and Drug Administration as first disease-modifying therapy (DMT) for multiple sclerosis (MS) in 1993. Since that time, clinical trials real-world observational studies have demonstrated effectiveness of IFN therapies. The pivotal intramuscular β-1a phase III trial published 1996 to demonstrate a DMT could reduce accumulation sustained disability MS. Patient adherence treatment is higher with β-1a, given once weekly, than subcutaneous formulations requiring injections per week. Moreover, associated an increased incidence injection-site reactions neutralizing antibodies compared administration. In recent years, revisions MS diagnostic criteria improved clinicians' ability identify patients promoted use magnetic resonance imaging (MRI) diagnosis disease monitoring. MRI show relative placebo, reduces T2 gadolinium-enhancing lesions gray matter atrophy. approval number high-efficacy therapies been MS, though benefit these should be balanced against risk serious adverse events their long-term use. For some subpopulations patients, including pregnant women, safety profile β may provide particular benefit. addition, antiviral properties IFNs indicate potential therapeutic opportunities reducing viral infections such COVID-19.

Language: Английский

Citations

49