Zhou Yijun, Shi Ce, Sun Hongchen
Department of Endodontics, Hospital of Stomatology, Jilin University, Changchun 130021, China.
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun 130021, China.
J Zhejiang Univ Sci B. 2025 Apr 23;26(4):317-332. doi: 10.1631/jzus.B2300779.
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital bilateral malformation of the large toe and progressive, extensive, and irreversible heterotopic ossification (HO) of soft tissues throughout the body, leading to severe disabilities. FOP is caused primarily by mutations in activin A receptor type 1 (), also known as activin-like kinase 2 (), which encodes a receptor belonging to the bone morphogenetic protein (BMP) type I family. However, the continuous and complex process of HO in FOP is not yet fully understood, which has impeded the development of therapeutic drugs. Despite surgical removal of HO, which often results in recurrence and expansion of ossification, there is currently no definitive drug treatment available to completely prevent, halt, or reverse the progression of HO in FOP. Currently, researchers are intensively studying the pathogenesis of FOP at various stages and developing promising drug candidates, including saracatinib, palovarotene, and rapamycin. This review provides an overview of progress in understanding the mechanism of FOP and the development of therapeutic drugs, with the goal of providing insights for further research and the development of new treatment methods.
进行性骨化性纤维发育不良（FOP）是一种罕见的遗传性疾病，其特征为大脚趾先天性双侧畸形，以及全身软组织进行性、广泛性和不可逆的异位骨化（HO），导致严重残疾。FOP主要由1型激活素A受体（ACVR1）突变引起，ACVR1也被称为激活素样激酶2（ALK2），它编码一种属于骨形态发生蛋白（BMP）I型家族的受体。然而，FOP中HO持续且复杂的过程尚未完全了解，这阻碍了治疗药物的开发。尽管手术切除HO通常会导致骨化复发和扩大，但目前尚无明确的药物治疗方法可完全预防、阻止或逆转FOP中HO的进展。目前，研究人员正在深入研究FOP各个阶段的发病机制，并开发有前景的候选药物，包括萨拉替尼、帕罗西汀和雷帕霉素。本综述概述了在理解FOP机制和治疗药物开发方面的进展，目的是为进一步研究和开发新的治疗方法提供见解。
