Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease that is characterized by the formation of heterotopic bone tissues in soft tissues, such as skeletal muscle, ligament, and tendon. It is difficult to remove such heterotopic bones via internal medicine or invasive procedures. The identification of activin A receptor, type I (ACVR1)/ALK2 gene mutations associated with FOP has allowed the genetic diagnosis of FOP. The ACVR1/ALK2 gene encodes the ALK2 protein, which is a transmembrane kinase receptor in the transforming growth factor-β family. The relevant mutations activate intracellular signaling in vitro and induce heterotopic bone formation in vivo. Activin A is a potential ligand that activates mutant ALK2 but not wild-type ALK2. Various types of small chemical and biological inhibitors of ALK2 signaling have been developed to establish treatments for FOP. Some of these are in clinical trials in patients with FOP.

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• How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva
  Dushyanth Srinivasan, Martin Arostegui, Erich J. Goebel, Kaitlin N. Hart, Senem Aykul, John B. Lees-Shepard, Vincent Idone, Sarah J. Hatsell, Aris N. Economides
  Biomolecules.2024; 14(1): 101.     CrossRef
• Fibrodysplasia Ossificans Progressiva Mimics Generalized Dystonia Disorder: A Case Report
  Seraj Makkawi, Osama Khojah, Reema Abualnaja, Abdulaziz Qashqari, Nawaf A Alahmadi, Abdullatif G Bshnaq, Abdulrahman Alharthi, Hashem H Al-Hashemi, Aiman M Shawli
  Cureus.2023;[Epub]     CrossRef
• Exploration of marine natural resources in Indonesia and development of efficient strategies for the production of microbial halogenated metabolites
  Hiroyuki Yamazaki
  Journal of Natural Medicines.2022; 76(1): 1.     CrossRef
• A Novel De Novo Frameshift Pathogenic Variant in the FAM111B Resulting in Progressive Osseous Heteroplasia Phenotype
  Anna Ryabets-Lienhard, Panadeekarn Panjawatanan, Kyle Vogt, Jianling Ji, Senta Georgia, Pisit Pitukcheewanont
  Calcified Tissue International.2022; 112(4): 518.     CrossRef
• Inhibitory effects of sesquiterpene lactones from the Indonesian marine sponge Lamellodysidea cf. herbacea on bone morphogenetic protein-induced osteoblastic differentiation
  Satoshi Ohte, Hiroyuki Yamazaki, Ohgi Takahashi, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Delfly B. Abdjul, Wilmar Maarisit, Magie M. Kapojos, Huiping Zhang, Fumiaki Hayashi, Michio Namikoshi, Takenobu Katagiri, Hiroshi Tomoda, Ryuji Uchid
  Bioorganic & Medicinal Chemistry Letters.2021; 35: 127783.     CrossRef
• Genomic Context and Mechanisms of the ACVR1 Mutation in Fibrodysplasia Ossificans Progressiva
  Roberto Ravazzolo, Renata Bocciardi
  Biomedicines.2021; 9(2): 154.     CrossRef
• New insights on fibrodysplasia ossificans progressiva: discussion of an autoptic case report and brief literature review
  Vittorio Bolcato, Claudia Carelli, Silvia Damiana Visonà, Marcella Reguzzoni, Maja Di Rocco, Alessandra Radogna, Livio Pietro Tronconi, Matteo Moretti
  Intractable & Rare Diseases Research.2021; 10(2): 136.     CrossRef
• Accumulated Knowledge of Activin Receptor-Like Kinase 2 (ALK2)/Activin A Receptor, Type 1 (ACVR1) as a Target for Human Disorders
  Takenobu Katagiri, Sho Tsukamoto, Mai Kuratani
  Biomedicines.2021; 9(7): 736.     CrossRef
• Cytoskeleton Reorganization in EndMT—The Role in Cancer and Fibrotic Diseases
  Wojciech Michał Ciszewski, Marta Ewelina Wawro, Izabela Sacewicz-Hofman, Katarzyna Sobierajska
  International Journal of Molecular Sciences.2021; 22(21): 11607.     CrossRef
• Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate
  Juliana Souza Vieira, Emanuelle Juliana Cunha, Juliana Feltrin de Souza, Luis Henrique Koeler Chaves, Jessica Lakes de Souza, Allan Fernando Giovanini
  World Journal of Experimental Medicine.2020; 10(1): 1.     CrossRef
• ALK2: A Therapeutic Target for Fibrodysplasia Ossificans Progressiva and Diffuse Intrinsic Pontine Glioma
  Katsuhiko Sekimata, Tomohiro Sato, Naoki Sakai
  Chemical and Pharmaceutical Bulletin.2020; 68(3): 194.     CrossRef
• Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases
  Riko Nishimura, Kenji Hata, Yoshifumi Takahata, Tomohiko Murakami, Eriko Nakamura, Maki Ohkawa, Lerdluck Ruengsinpinya
  International Journal of Molecular Sciences.2020; 21(4): 1340.     CrossRef
• Design of primers for direct sequencing of nine coding exons in the human ACVR1 gene
  Masaru Matsuoka, Sho Tsukamoto, Yuta Orihara, Rieko Kawamura, Mai Kuratani, Nobuhiko Haga, Kenji Ikebuchi, Takenobu Katagiri
  Bone.2020; 138: 115469.     CrossRef
• A new diketopiperazine-like inhibitor of bone morphogenetic protein-induced osteoblastic differentiation produced by marine-derived Aspergillus sp. BFM-0085
  Satoshi Ohte, Takehiro Shiokawa, Nobuhiro Koyama, Takenobu Katagiri, Chiaki Imada, Hiroshi Tomoda
  The Journal of Antibiotics.2020; 73(8): 554.     CrossRef
• Penicillic Acid Congener, a New Inhibitor of BMP-Induced Alkaline Phosphatase Activity in Myoblasts, Produced by the Fungus Penicillium sp. BF-0343
  Nobuhiro Koyama, Yasuhiro Otoguro, Satoshi Ohte, Takenobu Katagiri, Hiroshi Tomoda
  Natural Product Communications.2020; 15(9): 1934578X2094265.     CrossRef
• Fibrodysplasia ossificans progressiva: current concepts from bench to bedside
  Arun-Kumar Kaliya-Perumal, Tom J. Carney, Philip W. Ingham
  Disease Models & Mechanisms.2020;[Epub]     CrossRef
• Clinical Aspects and Current Therapeutic Approaches for FOP
  Hiroshi Kitoh
  Biomedicines.2020; 8(9): 325.     CrossRef
• Screening for Small Molecule Inhibitors of BMP-Induced Osteoblastic Differentiation from Indonesian Marine Invertebrates
  Hiroyuki Yamazaki, Satoshi Ohte, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Delfly B. Abdjul, Wilmar Maarisit, Magie M. Kapojos, Michio Namikoshi, Takenobu Katagiri, Hiroshi Tomoda, Ryuji Uchida
  Marine Drugs.2020; 18(12): 606.     CrossRef
• Propranolol and ascorbic acid in control of fibrodysplasia ossificans progressiva flare-ups due to accidental falls
  Durval Batista Palhares, Deborah Ribeiro Nascimento, Marilene Garcia Palhares, Suzana Lopes Bomfim Balaniuc, Liane de Rosso Giuliani, Paula Cristhina Niz Xavier, José Mauro Goulart Brum, Fabiana Alves, Francisco Oliveira Vieira, Elaine Maria Souza-Fagunde
  Intractable & Rare Diseases Research.2019; 8(1): 24.     CrossRef
• Late-onset fibrodysplasia ossificans progressiva with atypical presentation: A case report
  Conor M. Cunningham, J. Matthew Royeca, Samuel W. King, Hemant Pandit
  Case Reports in Women's Health.2019; 23: e00134.     CrossRef
• Fibrodysplasia ossificans progressiva: lessons learned from a rare disease
  Gulseren Akyuz, Kardelen Gencer-Atalay, Pinar Ata
  Current Opinion in Pediatrics.2019; 31(6): 716.     CrossRef
• Discovery of Heterotopic Bone-Inducing Activity in Hard Tissues and the TGF-β Superfamily
  Takenobu Katagiri, Sho Tsukamoto, Yutaka Nakachi, Mai Kuratani
  International Journal of Molecular Sciences.2018; 19(11): 3586.     CrossRef