Targeting B Cells to Modify MS, NMOSD, and MOGAD

Graf, Jonas; Mareś, Jan; Barnett, Michael; Aktaş, Orhan; Albrecht, Philipp; Zamvil, Scott S.; Hartung, Hans‐Peter

doi:10.1212/nxi.0000000000000918

Cited by 48 publications

(29 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…• Future treatment directions: (1) B-cell depleting monoclonal antibodies other than rituximab have poorly been studied in MOGAD. These include other anti-CD20 agents (e.g., ocrelizumab, ofatumumab) and anti-CD19 agents (e.g., inebilizumab) (183,184). These drugs can reasonably be considered alternatives to rituximab in MOGAD due to the similar mechanisms of action.…”

Section: Maintenance Treatmentmentioning

confidence: 99%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

et al. 2022

View full text Add to dashboard Cite

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is the most recently defined inflammatory demyelinating disease of the central nervous system (CNS). Over the last decade, several studies have helped delineate the characteristic clinical-MRI phenotypes of the disease, allowing distinction from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). The clinical manifestations of MOGAD are heterogeneous, ranging from isolated optic neuritis or myelitis to multifocal CNS demyelination often in the form of acute disseminated encephalomyelitis (ADEM), or cortical encephalitis. A relapsing course is observed in approximately 50% of patients. Characteristic MRI features have been described that increase the diagnostic suspicion (e.g., perineural optic nerve enhancement, spinal cord H-sign, T2-lesion resolution over time) and help discriminate from MS and AQP4+NMOSD, despite some overlap. The detection of MOG-IgG in the serum (and sometimes CSF) confirms the diagnosis in patients with compatible clinical-MRI phenotypes, but false positive results are occasionally encountered, especially with indiscriminate testing of large unselected populations. The type of cell-based assay used to evaluate for MOG-IgG (fixed vs. live) and antibody end-titer (low vs. high) can influence the likelihood of MOGAD diagnosis. International consensus diagnostic criteria for MOGAD are currently being compiled and will assist in clinical diagnosis and be useful for enrolment in clinical trials. Although randomized controlled trials are lacking, MOGAD acute attacks appear to be very responsive to high dose steroids and plasma exchange may be considered in refractory cases. Attack-prevention treatments also lack class-I data and empiric maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the presenting attack. A variety of empiric steroid-sparing immunosuppressants can be considered and may be efficacious based on retrospective or prospective observational studies but prospective randomized placebo-controlled trials are needed to better guide treatment. In summary, this article will review our rapidly evolving understanding of MOGAD diagnosis and management.

show abstract

Section: Maintenance Treatmentmentioning

confidence: 99%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Cladribine seems to act on an early phase of the pathological cascades of both conditions, inhibiting downstream pathological events [18]. The drug displays activity against both T and B cells, which differs from other effective drugs used in both conditions like B-cell depleting monoclonal antibodies [4,5]. Further investigation is necessary to determine whether the dual action of cladribine could prove more efficient in NMOSD.…”

Section: Discussionmentioning

confidence: 99%

Cladribine suppresses disease activity in neuromyelitis optica spectrum disorder: a 2‐year follow‐up study

Rejdak

Papuć

2021

Euro J of Neurology

View full text Add to dashboard Cite

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, inflammatory, B-cell mediated autoimmune disease affecting the central nervous system (CNS) with severe consequences [1]. Neurological episodes (relapses) are typically severe with partial recovery, leading to sustained disability. Most patients with NMOSD have detectable levels of autoantibodies to aquaporin-4 (AQP4), a membrane water channel expressed in astrocytes. Accumulated evidence suggests that this antibody is pathogenic [2]. Binding of AQP4 immunoglobulin G (IgG) to AQP4 activates complementdependent cytotoxicity, which leads to a cascade of inflammatory events including leukocyte infiltration and cytokine release along with breakdown of the blood-brain barrier (BBB). These inflammatory events result in demyelination and axonal damage, leading to the observed neurological deficits [3]. NMOSD is a difficult condition to treat and new therapeutic options are needed to provide effective and safe drugs that are also acceptable for

show abstract

“…We note that meningeal T cell infiltration has been seen before the appearance of clinical signs and even prior to dissemination into the CNS parenchyma 33 , 34 , indicating that this initial step is a potential T cell checkpoint in early disease pathology 35 . In addition, subpial aggregates of B cells and CD8 + T cells have been implicated as drivers of compartmentalized inflammation during the progressive stages of the disease 36 , 37 .…”

Section: Pathophysiology and Therapeuticsmentioning

confidence: 99%

Thinking outside the box: non-canonical targets in multiple sclerosis

Bierhansl

Hartung

Aktaş

et al. 2022

Nat Rev Drug Discov

Self Cite

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that causes demyelination, axonal degeneration and astrogliosis, resulting in progressive neurological disability. Fuelled by an evolving understanding of MS immunopathogenesis, the range of available immunotherapies for clinical use has expanded over the past two decades. However, MS remains an incurable disease and even targeted immunotherapies often fail to control insidious disease progression, indicating the need for new and exceptional therapeutic options beyond the established immunological landscape. In this Review, we highlight such non-canonical targets in preclinical MS research with a focus on five highly promising areas: oligodendrocytes; the blood–brain barrier; metabolites and cellular metabolism; the coagulation system; and tolerance induction. Recent findings in these areas may guide the field towards novel targets for future therapeutic approaches in MS.

show abstract

Targeting B Cells to Modify MS, NMOSD, and MOGAD

Cited by 48 publications

References 62 publications

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Cladribine suppresses disease activity in neuromyelitis optica spectrum disorder: a 2‐year follow‐up study

Thinking outside the box: non-canonical targets in multiple sclerosis

Contact Info

Product

Resources

About