Therapeutic Advances in Multiple Sclerosis

Yang, Jennifer H.; Rempe, Torge; Whitmire, Natalie; Dunn-Pirio, Anastasie M.; Graves, Jennifer

doi:10.3389/fneur.2022.824926

Cited by 58 publications

(43 citation statements)

References 152 publications

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“…Yet, as exemplified by MS, relapses and remission are treated distinctively, indicating that heterogeneous processes prevail at different stages of the disease. In fact, steroids and TPE are used to treat acute clinical deteriorations while disease modifying therapies (DMTs) are administered during remission to prevent further relapses [ 21 , 22 ]. Future studies should investigate the impact of anti-CD20 medications and TPE on cytokines and other inflammatory substances to determine the common denominator responsible for the treatment response of both therapies.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Aspects of Therapeutic Plasma Exchange in Neurological Disorders—A Pilot Study

Foettinger

Pilz

Wipfler

et al. 2023

IJMS

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Therapeutic plasma exchange (TPE) is used for drug-resistant neuroimmunological disorders, but its mechanism of action remains poorly understood. We therefore prospectively explored changes in soluble, humoral, and cellular immune components associated with TPE. We included ten patients with neurological autoimmune disorders that underwent TPE and assessed a panel of clinically relevant pathogen-specific antibodies, total serum immunoglobulin (Ig) levels, interleukin-6 (IL-6, pg/mL), C-reactive protein (CRP, mg/dL), procalcitonin (PCT, µg/L) and major lymphocyte subpopulations (cells/µL). Blood was collected prior to TPE (pre-TPE, baseline), immediately after TPE (post-TPE), as well as five weeks (follow-up1) and 130 days (follow-up2) following TPE. Pathogen-specific antibody levels were reduced by −86% (p < 0.05) post-TPE and recovered to 55% (follow-up1) and 101% (follow-up2). Ig subclasses were reduced by −70–89% (p < 0.0001) post-TPE with subsequent complete (IgM/IgA) and incomplete (IgG) recovery throughout the follow-ups. Mean IL-6 and CRP concentrations increased by a factor of 3–4 at post-TPE (p > 0.05) while PCT remained unaffected. We found no alterations in B- and T-cell populations. No adverse events related to TPE occurred. TPE induced a profound but transient reduction in circulating antibodies, while the investigated soluble immune components were not washed out. Future studies should explore the effects of TPE on particular cytokines and assess inflammatory lymphocyte lineages to illuminate the mode of action of TPE beyond autoantibody removal.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Aspects of Therapeutic Plasma Exchange in Neurological Disorders—A Pilot Study

Foettinger

Pilz

Wipfler

et al. 2023

IJMS

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“…The MS pathogenesis is still under discussion, although it is known that there are confirmed risk factors, such as the presence of the allele HLA- DRB1*1501 in the MHC complex of affected subjects and environmental factors like vitamin D level, obesity, smoking, and the Epstein-Barr virus (EBV) infection [ 13 ].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities

Bianco

Antonacci

Liguori

2023

IJMS

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The term “neurodegenerative diseases” (NDs) identifies a group of heterogeneous diseases characterized by progressive loss of selectively vulnerable populations of neurons, which progressively deteriorates over time, leading to neuronal dysfunction. Protein aggregation and neuronal loss have been considered the most characteristic hallmarks of NDs, but growing evidence confirms that significant dysregulation of innate immune pathways plays a crucial role as well. NDs vary from multiple sclerosis, in which the autoimmune inflammatory component is predominant, to more “classical” NDs, such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. Of interest, many of the clinical differences reported in NDs seem to be closely linked to sex, which may be justified by the significant changes in immune mechanisms between affected females and males. In this review, we examined some of the most studied NDs by looking at their pathogenic and phenotypical features to highlight sex-related discrepancies, if any, with particular interest in the individuals’ responses to treatment. We believe that pointing out these differences in clinical practice may help achieve more successful precision and personalized care.

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“…DMTs for MS include immune modulators such as β-interferons, glatiramer acetate, teriflunomide, cladribine, natalizumab, and dimethyl fumarate; S1P receptor modulators, including fingolimod, ozanimod, siponimod, and ponesimod; and agents that deplete CD20+ B cells, including ocrelizumab and ofatumumab. 26 "Early on [in the pandemic]," explained Shin, "there was a concern that patients with MS might be extra vulnerable and that DMTs could increase vulnerability to COVID-19, particularly the categories of medicines that are perceived to be more immunosuppressive." This, Shin discussed, led to some prescribers delaying certain treatments at the start of the pandemic, although, in general, Shin reported that this is no longer occurring.…”

Section: Covid-19 Infection Sars-cov-2 Vaccinations and Disease Modif...mentioning

confidence: 99%

The Efficacy and Safety of SARS-CoV-2 Vaccinations in People with Multiple Sclerosis

Roberts¹

2023

EMJ Neurol

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While people with multiple sclerosis (MS) are not more likely to contract COVID-19, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related complications may be higher for people with MS who have comorbidities or who are taking certain disease modifying therapies (DMT). Robert Shin, Professor of Neurology at MedStar Georgetown University Hospital, Washington, D.C., USA, and Deborah Fuller, Department of Microbiology, University of Washington School of Medicine, and Associate Director of the Washington National Primate Research Center, Seattle, Washington, USA, first discussed why vaccinations against SARS-CoV-2 should be recommended to people with MS. They then discussed evidence that suggests that the antibody response following vaccination may be dampened in people taking some DMTs, especially those that deplete CD20+ B cells; however, T cell responses to vaccinations may also provide protection. There is also evidence that messenger RNA (mRNA) SARS-CoV-2 vaccines, as opposed to viral vector or recombinant protein subunit vaccines, and boosters may lead to a better antibody response. Vaccine responses vary between patients taking different sphinogosine-1-phosphate (S1P) receptor modulators, being low for fingolimod and high for next generation S1P receptor modulators. Overall, more studies of vaccine response and timing are needed to best update the guidelines for people with MS.

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Therapeutic Advances in Multiple Sclerosis

Cited by 58 publications

References 152 publications

Immunomodulatory Aspects of Therapeutic Plasma Exchange in Neurological Disorders—A Pilot Study

Immunomodulatory Aspects of Therapeutic Plasma Exchange in Neurological Disorders—A Pilot Study

Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities

The Efficacy and Safety of SARS-CoV-2 Vaccinations in People with Multiple Sclerosis

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