Multifocal motor neuropathy

Beadon, K; Guimarães‐Costa, Raquel; Léger, Jean‐Marc

doi:10.1097/wco.0000000000000605

Cited by 76 publications

(38 citation statements)

References 40 publications

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“…Patients with MMN are most commonly middle‐aged males who present with progressive, predominantly upper limb deficits 7 . These may cause varying degrees of functional impairment, and disability levels may be relatively mild 8 .…”

Section: Diagnostic Considerationsmentioning

confidence: 99%

Management challenges for chronic dysimmune neuropathies during the COVID‐19 pandemic

et al. 2020

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Since March 2020, the COVID‐19 pandemic has led to the need to re‐think the delivery of services to patients with chronic dysimmune neuropathies. Telephone/video consultations have become widespread but have compounded concerns about objective evaluation. Therapeutic decisions need, more than ever before, to be considered in the best interests of both patients, and society, while not denying function‐preserving/restoring treatment. Immunoglobulin therapy and plasma exchange, for those treated outside of the home, expose patients to the hazards of hospital or outpatient infusion centers. Steroid therapy initiation and continuation pose increased infectious risk. Immunosuppressant therapy similarly becomes highly problematic, with the risks of treatment continuation enhanced by uncertainties regarding duration of the pandemic. The required processes necessitate considerable time and effort especially as resources and staff are re‐deployed to face the pandemic, but are essential for protecting this group of patients and as an integral part of wider public health actions.

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Section: Diagnostic Considerationsmentioning

confidence: 99%

Management challenges for chronic dysimmune neuropathies during the COVID‐19 pandemic

et al. 2020

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“…The term MMN was introduced by Pestronk et al when reporting 2 patients with a motor neuropathy associated with high titres of IgM antibodies directed against GM1. The diagnosis of MMN is based on clinical, electrophysiological, and laboratory characteristics . Clinical features consist of slowly progressive, asymmetric muscle weakness of distal limbs, affecting at least 2 nerves in more than 1 limb.…”

Section: Multifocal Motor Neuropathy (Mmn)mentioning

confidence: 99%

Boundaries of chronic inflammatory demyelinating polyradiculoneuropathy

Bergh

Doorn

Jacobs

et al. 2020

J Peripheral Nervous Sys

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“…This is thought to interfere with axon-Schwann cell interactions, causing widening of the node and axonal damage. 1,2,6 Presence and titers of IgM anti-GM1 antibodies, as well as their complement activating properties, correlate with clinical features such as weakness and axonal damage. 7 Moreover, the binding of anti-GM1 IgM from patients to motor neurons (MNs) derived from induced pluripotent stem cells (iPSCs) and subsequent activation of the classical complement pathway causes disturbed calcium homeostasis and structural damage of these cells in vitro resembling changes occurring in MMN.…”

mentioning

confidence: 99%

Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy

Budding

Johansen

Walle

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesTo determine the role of complement in the disease pathology of multifocal motor neuropathy (MMN), we investigated complement activation, and inhibition, on binding of MMN patient-derived immunoglobulin M (IgM) antibodies in an induced pluripotent stem cell (iPSC)-derived motor neuron (MN) model for MMN.MethodsiPSC-derived MNs were characterized for the expression of complement receptors and membrane-bound regulators, for the binding of circulating IgM anti-GM1 from patients with MMN, and for subsequent fixation of C4 and C3 on incubation with fresh serum. The potency of ARGX-117, a novel inhibitory monoclonal antibody targeting C2, to inhibit fixation of complement was assessed.ResultsiPSC-derived MNs moderately express the complement regulatory proteins CD46 and CD55 and strongly expressed CD59. Furthermore, MNs express C3aR, C5aR, and complement receptor 1. IgM anti-GM1 antibodies in serum from patients with MMN bind to MNs and induce C3 and C4 fixation on incubation with fresh serum. ARGX-117 inhibits complement activation downstream of C4 induced by patient-derived anti-GM1 antibodies bound to MNs.DiscussionBinding of IgM antibodies from patients with MMN to iPSC-derived MNs induces complement activation. By expressing complement regulatory proteins, particularly CD59, MNs are protected against complement-mediated lysis. Yet, because of expressing C3aR, the function of these cells may be affected by complement activation upstream of membrane attack complex formation. ARGX-117 inhibits complement activation upstream of C3 in this disease model for MMN and therefore represents an intervention strategy to prevent harmful effects of complement in MMN.

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Multifocal motor neuropathy

Cited by 76 publications

References 40 publications

Management challenges for chronic dysimmune neuropathies during the COVID‐19 pandemic

Management challenges for chronic dysimmune neuropathies during the COVID‐19 pandemic

Boundaries of chronic inflammatory demyelinating polyradiculoneuropathy

Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy

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