ArticleThe Journal of clinical investigation2022
Anti-ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 62 citations in OpenAlex.
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- Fibrodysplasia ossificans progressiva: genetic and clinical characterization in a cohort of Polish patients and review of potential therapies.Journal of applied genetics · 2026Review
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- CryoEM structure of ALK2:BMP6 reveals distinct mechanism that allow ALK2 to interact with both BMP and activin ligands.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Crosstalk Between Skeletal Muscle and Proximal Connective Tissues in Lipid Dysregulation in Obesity and Type 2 Diabetes.Metabolites · 2025Review
- Developing HaloTag and SNAP-Tag Chemical Inducers of Dimerization to Probe Receptor Oligomerization and Downstream Signaling.Angewandte Chemie (International ed. in English) · 2025Article
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- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- Heterotopic ossification: Current developments and emerging potential therapies.Chinese medical journal · 2025Review
- Targeting to BMP9 to restrain flare-up of fibrodysplasia ossificans progressiva.EMBO molecular medicine · 2025Article
- Iliopsoas myositis ossificans after transverse myelitis in a child: a case report.Frontiers in surgery · 2025Article
- Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single-Cell Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Immunologic Aspects in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
- The prognostic value and potential immunotherapeutic efficacy ofJournal of gastrointestinal oncology · 2024Article
- Acute fracture of an extensively ossified segment of the Achilles tendon.BMJ case reports · 2024Article
- Context-dependent TGFβ family signalling in cell fate regulation.Nature reviews. Molecular cell biology · 2023Review
- Review
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21 authors at 3 institutions in 1 country.
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Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder whose most debilitating pathology is progressive and cumulative heterotopic ossification (HO) of skeletal muscles, ligaments, tendons, and fascia. FOP is caused by mutations in the type I BMP receptor gene ACVR1, which enable ACVR1 to utilize its natural antagonist, activin A, as an agonistic ligand. The physiological relevance of this property is underscored by the fact that HO in FOP is exquisitely dependent on activation of FOP-mutant ACVR1 by activin A, an effect countered by inhibition of anti-activin A via monoclonal antibody treatment. Hence, we surmised that anti-ACVR1 antibodies that block activation of ACVR1 by ligands should also inhibit HO in FOP and provide an additional therapeutic option for this condition. Therefore, we generated anti-ACVR1 monoclonal antibodies that block ACVR1's activation by its ligands. Surprisingly, in vivo, these anti-ACVR1 antibodies stimulated HO and activated signaling of FOP-mutant ACVR1. This property was restricted to FOP-mutant ACVR1 and resulted from anti-ACVR1 antibody-mediated dimerization of ACVR1. Conversely, wild-type ACVR1 was inhibited by anti-ACVR1 antibodies. These results uncover an additional property of FOP-mutant ACVR1 and indicate that anti-ACVR1 antibodies should not be considered as therapeutics for FOP.
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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.