ArticleThe Journal of clinical investigation2022
An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice.
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 26 papers.
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26 citing papers in PubMed, 41 citations in OpenAlex.
- Pathogenic transcriptional reprogramming of fibro-adipogenic progenitors in mice with FOP and its mitigation by inhibition of ACVR1 and activin A.bioRxiv : the preprint server for biology · 2026Article
- Article
- Activation of PPARγ redirects fibro-adipogenic progenitors to replace ectopic bone with fat in models of fibrodysplasia ossificans progressiva and trauma-induced heterotopic ossification.bioRxiv : the preprint server for biology · 2026Article
- The role of muscle fascia in heterotopic ossification and maintenance of skeletal muscle integrity in fibrodysplasia ossificans progressiva.bioRxiv : the preprint server for biology · 2025Article
- GNAS/PKA signaling promotes aberrant osteochondral differentiation of Gli1The EMBO journal · 2025Article
- Article
- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- Targeted allele-specificMolecular therapy. Nucleic acids · 2025Article
- PdgfrαGenes & diseases · 2025Review
- Heterotopic ossification: Current developments and emerging potential therapies.Chinese medical journal · 2025Review
- Fibrodysplasia ossificans progressiva: Two case reports.Radiology case reports · 2024Article
- Cellular and Molecular Mechanisms of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva.Biomedicines · 2024Review
- iMSC-mediated delivery of ACVR2B-Fc fusion protein reduces heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva.Stem cell research & therapy · 2024Article
- iMSC-mediated delivery of ACVR2B-Fc fusion protein reduces heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva.Stem cell research & therapy · 2024Article
- Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.Biomolecules · 2024Review
- Sex as a Critical Variable in Basic and Pre-Clinical Studies of Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Article
- Sex as a Critical Variable in Basic and Pre-Clinical Studies of Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Article
- How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
- How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
- Context-dependent TGFβ family signalling in cell fate regulation.Nature reviews. Molecular cell biology · 2023Review
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9 authors at 2 institutions in 1 country.
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Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive and catastrophic heterotopic ossification (HO) of skeletal muscle and associated soft tissues. FOP is caused by dominantly acting mutations in the gene encoding the bone morphogenetic protein (BMP) type I receptor, ACVR1 (ALK2), the most prevalent of which results in an arginine to histidine substitution at position 206 (ACVR1[R206H]). The fundamental pathological consequence of FOP-causing ACVR1 receptor mutations is to enable activin A to initiate canonical BMP signaling in fibro-adipogenic progenitors (FAPs), which drives HO. We developed a monoclonal blocking antibody (JAB0505) against the extracellular domain of ACVR1 and tested its effect on HO in 2 independent FOP mouse models. Although JAB0505 inhibited BMP-dependent gene expression in wild-type and ACVR1(R206H)-overexpressing cell lines, JAB0505 treatment profoundly exacerbated injury-induced HO. JAB0505-treated mice exhibited multiple, distinct foci of heterotopic lesions, suggesting an atypically broad anatomical domain of FAP recruitment to endochondral ossification. This was accompanied by dysregulated FAP population growth and an abnormally sustained immunological reaction following muscle injury. JAB0505 drove injury-induced HO in the absence of activin A, indicating that JAB0505 has receptor agonist activity. These data raise serious safety and efficacy concerns for the use of bivalent anti-ACVR1 antibodies to treat patients with FOP.
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