Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair

Havla, Joachim; Hohlfeld, Reinhard

doi:10.1007/s13311-022-01214-x

Cited by 8 publications

(3 citation statements)

References 99 publications

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“…There is increasing evidence that the pathological mechanisms of PMS and RRMS are different. While relapses are thought to be caused by acute focal inflammation, relapse-independent progression is the clinical consequence of more diffuse inflammatory and neurodegenerative processes [ 150 ]. Thus, high levels of mexDNA in RRMS might be predominantly due to active release in response to a stimulus, and could reflect early inflammatory activity rather than neuronal loss.…”

Section: Self-extracellular Nucleic Acids In Neuroinflammatory Diseasesmentioning

confidence: 99%

Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration

Kunze,

Fischer,

Marti

et al. 2023

J Biomed Sci

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Neurological disorders such as stroke, multiple sclerosis, as well as the neurodegenerative diseases Parkinson's or Alzheimer's disease are accompanied or even powered by danger associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue. Besides protein-related DAMPs or “alarmins”, numerous nucleic acid DAMPs exist in body fluids, such as cell-free nuclear and mitochondrial DNA as well as different species of extracellular RNA, collectively termed as self-extracellular nucleic acids (SENAs). Among these, microRNA, long non-coding RNAs, circular RNAs and extracellular ribosomal RNA constitute the majority of RNA-based DAMPs. Upon tissue injury, necrosis or apoptosis, such SENAs are released from neuronal, immune and other cells predominantly in association with extracellular vesicles and may be translocated to target cells where they can induce intracellular regulatory pathways in gene transcription and translation. The majority of SENA-induced signaling reactions in the brain appear to be related to neuroinflammatory processes, often causally associated with the onset or progression of the respective disease. In this review, the impact of the diverse types of SENAs on neuroinflammatory and neurodegenerative diseases will be discussed. Based on the accumulating knowledge in this field, several specific antagonistic approaches are presented that could serve as therapeutic interventions to lower the pathological outcome of the indicated brain disorders.

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Section: Self-extracellular Nucleic Acids In Neuroinflammatory Diseasesmentioning

confidence: 99%

Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration

Kunze,

Fischer,

Marti

et al. 2023

J Biomed Sci

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“…Although B cell-depleting antibody therapies are approved for treatment of RMS and primary-progressive MS (PPMS) [10–14], these agents only modestly limit disease progression [5,15,16,17 ▪ ].…”

Section: Introductionmentioning

confidence: 99%

Bruton tyrosine kinase inhibitors in multiple sclerosis: evidence and expectations

Krämer,

Wiendl

2024

Current Opinion in Neurology

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Purpose of review Despite availability of high-efficacy therapies for multiple sclerosis (MS), many patients experience significant disability worsening due to limited effects of currently available drugs on central nervous system (CNS)-compartmentalized inflammation. Bruton tyrosine kinase (BTK) is an intracellular signaling molecule involved in regulation of maturation, survival, migration, and activation of B cells and microglia, which are central players in the immunopathogenesis of progressive MS. Therefore, CNS-penetrant BTK inhibitors may better prevent disease progression by targeting immune cells on both sides of the blood–brain barrier. This review gives an overview on the preliminary results of clinical trials. Recent findings Currently, the efficacy and safety of six BTK inhibitors are being evaluated in clinical trials in patients with relapsing and progressive MS. Evobrutinib, tolebrutinib and fenebrutinib have shown efficacy and safety in relapsing MS in phase 2 studies, and evobrutinib and tolebrutinib in their extension studies up to 3–5 years. However, evobrutinib failed to distinguish itself from the comparator drug teriflunomide in reduction of relapse rate (primary end point) in two phase 3 studies in relapsing MS. Summary Inhibition of BTK has emerged as a promising therapeutic approach to target the CNS-compartmentalized inflammation. Results from phase 3 clinical trials will shed light on differences in efficacy and safety of BTK inhibitors and its potential role in the future MS landscape.

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“…The disease is provoked by hard demyelination and axonal degeneration leading to progressive damage of the nervous system and accumulation of persistent disability [1]. The autoimmune hypothesis involves the dysregulation of autoreactive T cells with B lymphocytes and macrophages, in which virusinduced immunopathology plays a relevant role [2].…”

Section: Introduction / вступmentioning

confidence: 99%

Differential Diagnosis of Exacerbations and Pseudo-Exacerbations Against the Background of Sars-Cov-2 by the Example of a Clinical Case of a Patient With Multiple Sclerosis

Lychko

Kolenko

Burtyka

2023

EUMJ

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Abstract. Due to the COVID-19 pandemic, there is an increasing need for information on how SARS-CoV-2 affects individuals with multiple sclerosis (MS). The patients receiving disease-modifying therapy (DMT) for MS are more likely to require medical attention for infection than the general population. SARS-CoV-2 can cause the worsening of MS symptoms and be mistaken for a relapse, so physicians must carefully assess whether a patient is experiencing a relapse or pseudo-exacerbation. Thus, there is a necessity for science-based guidelines on how to lower the risk of infection, as well as an early differential diagnosis of relapse and pseudo-exacerbation, and effective care for MS patients with COVID-19. Materials and methods of research: a patient with a history of MS treated with DMTs. The patient presented with worsening disease symptoms, likely exacerbation, and was diagnosed with COVID-19. Results: a thorough analysis of existing literature was conducted, along with a quick examination of how DMT was used in MS patients with COVID-19. The patient we dealt with was receiving DMT and experienced a severe illness. Timely use of intravenous corticosteroids and antibiotics allowed taking under control the activity of the pathological process. Fortunately, the outcome was favorable. Conclusions: this evaluation presents information about the clinical features, results, and functions of DMTs in MS patients infected with SARS-CoV-2. Healthcare professionals must carefully consider the possibility of relapse in MS patients with COVID-19, particularly during the pandemic, and should look out for pseudo-exacerbations. While many cases demonstrated a mild course of illness and successful recovery with DMTs, additional investigation is required to create guidelines supported by evidence.

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Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair

Cited by 8 publications

References 99 publications

Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration

Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration

Bruton tyrosine kinase inhibitors in multiple sclerosis: evidence and expectations

Differential Diagnosis of Exacerbations and Pseudo-Exacerbations Against the Background of Sars-Cov-2 by the Example of a Clinical Case of a Patient With Multiple Sclerosis

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