ArticlemAbs
Functional activity of anti-LINGO-1 antibody opicinumab requires target engagement at a secondary binding site.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03222973 (A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With Optional Open-Label Extension in Subjects With Relapsing Multiple Sclerosis to Evaluate the Efficacy and Safety of BIIB033 as an Add-On Therapy to Anti-Inflammatory Disease-Modifying Therapies), which is not on this map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With Optional Open-Label Extension in Subjects With Relapsing Multiple Sclerosis to Evaluate the Efficacy and Safety of BIIB033 as an Add-On Therapy to Anti-Inflammatory Disease-Modifying Therapies
Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Emerging therapeutic strategies in multiple sclerosis: a focus on innovative and targeted approaches.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Oligodendrocyte dysfunction in neurodegenerative diseases: pathological features, underlying mechanisms and therapeutic targeting.Frontiers in aging neuroscience · 2026Review
- Primary Progressive Multiple Sclerosis: New Therapeutic Approaches.Neuropsychopharmacology reports · 2025Review
- Neuroprotective strategies in multiple sclerosis: a status update and emerging paradigms.Expert review of neurotherapeutics · 2025Review
- Demyelination and Remyelination: General Principles.Advances in neurobiology · 2025Review
- Nogo-A and LINGO-1: Two Important Targets for Remyelination and Regeneration.International journal of molecular sciences · 2023Review
- Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells.International journal of molecular sciences · 2023Article
- Nogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model.Brain communications · 2023Article
- A Glance at the Molecules That Regulate Oligodendrocyte Myelination.Current issues in molecular biology · 2022Review
- Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Article
- White Matter Damage in Alzheimer's Disease: Contribution of Oligodendrocytes.Current Alzheimer research · 2022Article
- A review of possible therapies for multiple sclerosis.Molecular and cellular biochemistry · 2021Review
- Review
- The Current Challenges for Drug Discovery in CNS Remyelination.International journal of molecular sciences · 2021Review
- Mechanism of delayed encephalopathy after acute carbon monoxide poisoning.Neural regeneration research · 2020Article
- Clinical Immunological Correlations in Patients with Multiple Sclerosis Treated with Natalizumab.Brain sciences · 2020Article
- Opicinumab: is it a potential treatment for multiple sclerosis?Annals of translational medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LINGO-1 is a membrane protein of the central nervous system (CNS) that suppresses myelination of axons. Preclinical studies have revealed that blockade of LINGO-1 function leads to CNS repair in demyelinating animal models. The anti-LINGO-1 antibody Li81 (opicinumab), which blocks LINGO-1 function and shows robust remyelinating activity in animal models, is currently being investigated in a Phase 2 clinical trial as a potential treatment for individuals with relapsing forms of multiple sclerosis (AFFINITY: clinical trial.gov number NCT03222973). Li81 has the unusual feature that it contains two LINGO-1 binding sites: a classical site utilizing its complementarity-determining regions and a cryptic secondary site involving Li81 light chain framework residues that recruits a second LINGO-1 molecule only after engagement of the primary binding site. Concurrent binding at both sites leads to formation of a 2:2 complex of LINGO-1 with the Li81 antigen-binding fragment, and higher order complexes with intact Li81 antibody. To elucidate the role of the secondary binding site, we designed a series of Li81 variant constructs that eliminate it while retaining the classic site contacts. These Li81 mutants retained the high affinity binding to LINGO-1, but lost the antibody-induced oligodendrocyte progenitor cell (OPC) differentiation activity and myelination activity in OPC- dorsal root ganglion neuron cocultures seen with Li81. The mutations also attenuate antibody-induced internalization of LINGO-1 on cultured cortical neurons, OPCs, and cells over-expressing LINGO-1. Together these studies reveal that engagement at both LINGO-1 binding sites of Li81 is critical for robust functional activity of the antibody.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.