Abstract
AbstractFibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disease caused by heterozygous missense mutations in Activin A receptor type I which is also known as Activin-like kinase 2 (ALK2), a type I receptor of Bone Morphogenetic Proteins(BMP). Patients with FOP usually undergo episodic flare-ups and the heterotopic ossification in soft and connective tissues. Molecular mechanism study indicates that Activin A, the ligand which normally transduces Transforming Growth Factor Beta signaling, abnormally activates BMP signaling through ALK2 mutants in FOP, leading to heterotopic bone formation. To date, effective therapies to FOP are unavailable. However, significant advances have recently been made in the development of FOP drugs. In this article, we review the recent advances in understanding the FOP mechanism and drug development, with a focus on the small-molecular and antibody drugs currently in the clinical trials for FOP treatment.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Clinical Biochemistry,Molecular Biology,General Medicine
Reference75 articles.
1. Kaplan FS, Shen Q, Lounev V, Seemann P, Groppe J, Katagiri T et al (2008) Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP). J Bone Miner Metab 26(6):521–530
2. Pignolo RJ, Shore EM, Kaplan FS (2013) Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatr Endocrinol Rev 10(Suppl 2):437–448
3. Kaplan FS, Xu M, Glaser DL, Collins F, Connor M, Kitterman J et al (2008) Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics 121(5):e1295–e1300
4. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH et al (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38(5):525–527
5. Furuya H, Ikezoe K, Wang L, Ohyagi Y, Motomura K, Fujii N et al (2008) A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H). Am J Med Genet A 146A(4):459–463
Cited by
12 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献