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

Background And Objectives: To 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.

Methods: iPSC-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.

Duplications Are Associated With Progressive Muscular Atrophy, but Not With Multifocal Motor Neuropathy and Primary Lateral Sclerosis.

Objective: To assess the association between copy number (CN) variation in the survival motor neuron () locus and multifocal motor neuropathy (MMN), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS) susceptibility and to determine the association of and CN with MMN, PMA, and PLS disease course.

Methods: In this monocenter study, we used multiplex ligation-dependent probe amplification to determine and CN in Dutch patients with MMN, PMA, and PLS and controls. We stratified clinical parameters for and CN.

Intragenic and structural variation in the locus and clinical variability in spinal muscular atrophy.

Clinical severity and treatment response vary significantly between patients with spinal muscular atrophy. The approval of therapies and the emergence of neonatal screening programmes urgently require a more detailed understanding of the genetic variants that underlie this clinical heterogeneity. We systematically investigated genetic variation other than copy number in the locus.

Analysis of , , and as potential disease severity modifiers in spinal muscular atrophy.

Objective: To investigate mutations in genes that are potential modifiers of spinal muscular atrophy (SMA) severity.

Methods: We performed a hypothesis-based search into the presence of variants in fused in sarcoma () transactive response DNA-binding protein 43 (), plastin 3 (), and profilin 2 () in a cohort of 153 patients with SMA types 1-4, including 19 families. Variants were detected with targeted next-generation sequencing and confirmed with Sanger sequencing.