Anti-CD52 Therapy for Multiple Sclerosis: An Update in the COVID Era

Kasarełło, Kaja; Mirowska‐Guzel, Dagmara

doi:10.2147/itt.s240890

Cited by 7 publications

(1 citation statement)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to involvement in angiogenesis, IFI30 marks the high infiltration of immune cells (51) and is highly enriched in ME group iii ( Fig2A ). Genes that are essential for the weakening of VE junctions ( TM4SF19 , (52)) and lymphocyte trans-endothelial migration ( CD52 , (53)) are highly enriched in the intralesional WM ( Fig2D ). Moreover, intralesional WM-enriched ME group iii (ME19, 13, 8) and ME18 ( Fig2E ) are marked by genes that are primarily expressed by immune cells ( MMP9 , FBP1 , S100A12 , GPNMB , CXCR4 , FigS7A-B ).…”

Section: Mainmentioning

confidence: 99%

A 4D transcriptomic map for the evolution of multiple sclerosis-like lesions in the marmoset brain

Lin,

Brake,

Donadieu

et al. 2023

Preprint

View full text Add to dashboard Cite

Single-time-point histopathological studies on postmortem multiple sclerosis (MS) tissue fail to capture lesion evolution dynamics, posing challenges for therapy development targeting development and repair of focal inflammatory demyelination. To close this gap, we studied experimental autoimmune encephalitis (EAE) in the common marmoset, the most faithful animal model of these processes. Using MRI-informed RNA profiling, we analyzed ∼600,000 single-nucleus and ∼55,000 spatial transcriptomes, comparing them against EAE inoculation status, longitudinal radiological signals, and histopathological features. We categorized 5 groups of microenvironments pertinent to neural function, immune and glial responses, tissue destruction and repair, and regulatory network at brain borders. Exploring perilesional microenvironment diversity, we uncovered central roles of EAE-associated astrocytes, oligodendrocyte precursor cells, and ependyma in lesion formation and resolution. We pinpointed imaging and molecular features capturing the pathological trajectory of WM, offering potential for assessing treatment outcomes using marmoset as a platform.One sentence summaryA cross-modality study to identify the spatiotemporal-based diversity of primate brain cells during white matter inflammatory demyelination to inform lesion detection, stratification, and management in multiple sclerosis.

show abstract

Section: Mainmentioning

confidence: 99%

A 4D transcriptomic map for the evolution of multiple sclerosis-like lesions in the marmoset brain

Lin,

Brake,

Donadieu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis

Albach,

Geier,

Keicher

et al. 2024

Neurol Ther

View full text Add to dashboard Cite

Introduction Lymphocyte depletion via anti-CD52 monoclonal antibody (mAb) therapy is an effective treatment strategy for relapsing–remitting multiple sclerosis (MS) but is associated with infusion/injection-associated reactions (IARs) and autoimmune-related adverse events (AEs). Gatralimab is a next-generation humanized anti-CD52 mAb. Methods Two first-in-human trials were conducted in participants with progressive MS to assess the pharmacodynamics, pharmacokinetics, and safety of gatralimab administered via subcutaneous (SC) and intravenous (IV) routes, and to determine the effect of different comedication regimes on IARs to SC gatralimab. A Phase 1 trial (NCT02282826) included double-blind, placebo-controlled sequential ascending single IV (1, 3.5, and 12 mg) and SC (12, 36, and 60 mg) dose groups. A Phase 1b trial (NCT02977533) involved five groups who received SC gatralimab (36, 48, or 60 mg) and different comedications. A long-term safety (LTS) study (NCT02313285) examined safety and pharmacodynamics over 4 years. Results Gatralimab produced depletion of lymphocytes (dose-dependently) and CD4+ regulatory T cells, with partial repopulation to normal values by approximately 12 months. Peak serum gatralimab concentrations followed dose-proportionality and were delayed by 6.0–7.5 days following SC administration. Treatment-emergent AEs, including IARs, were reported for most participants but were generally of mild or moderate severity, and treatment-emergent serious AEs were mostly MS-related. Methylprednisolone and antihistamine comedications were associated with reduced incidence of fevers and skin and subcutaneous tissue AEs, respectively. During the LTS study, one participant (3.0%) experienced an autoimmune-related AE (Basedow’s disease), and subsequently died from pulmonary sepsis deemed unrelated to gatralimab by the investigator. Conclusions These data show that gatralimab achieves the desired pharmacodynamic effect of lymphocyte depletion followed by repopulation, and has an acceptable safety profile, including low risk of non-MS autoimmunity. Although gatralimab is no longer in development for MS, insights from these trials may inform the development of comedication regimes of future anti-CD52 mAbs and subcutaneous formulations of other lymphocyte-depleting mAbs. Trial registration NCT02282826, NCT02977533, NCT02313285. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-024-00659-w.

show abstract

Multiple sclerosis: a narrative overview of current pharmacotherapies and emerging treatment prospects

Olejnik,

Roszkowska,

Adamus

et al. 2024

Pharmacol. Rep

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by pathological processes of demyelination, subsequent axonal loss, and neurodegeneration within the central nervous system. Despite the availability of numerous disease-modifying therapies that effectively manage this condition, there is an emerging need to identify novel therapeutic targets, particularly for progressive forms of MS. Based on contemporary insights into disease pathophysiology, ongoing efforts are directed toward developing innovative treatment modalities. Primarily, monoclonal antibodies have been extensively investigated for their efficacy in influencing specific pathological pathways not yet targeted. Emerging approaches emphasizing cellular mechanisms, such as chimeric antigen receptor T cell therapy targeting immunological cells, are attracting increasing interest. The evolving understanding of microglia and the involvement of ferroptotic mechanisms in MS pathogenesis presents further avenues for targeted therapies. Moreover, innovative treatment strategies extend beyond conventional approaches to encompass interventions that target alterations in microbiota composition and dietary modifications. These adjunctive therapies hold promise as complementary methods for the holistic management of MS. This narrative review aims to summarize current therapies and outline potential treatment methods for individuals with MS.

show abstract

Anti-CD52 Therapy for Multiple Sclerosis: An Update in the COVID Era

Cited by 7 publications

References 68 publications

A 4D transcriptomic map for the evolution of multiple sclerosis-like lesions in the marmoset brain

A 4D transcriptomic map for the evolution of multiple sclerosis-like lesions in the marmoset brain

Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis

Multiple sclerosis: a narrative overview of current pharmacotherapies and emerging treatment prospects

Contact Info

Product

Resources

About