Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva

Yijun ZHOU; Ce SHI; Hongchen SUN

doi:10.1631/jzus.B2300779

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Review | Updated：2025-04-23

Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva
Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva
进行性骨化性纤维发育不良的发病机制及药物治疗的研究进展
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 4, Pages: 317-332(2025)
Affiliations：

1.Department of Endodontics, Hospital of Stomatology, Jilin University, Changchun 130021, China
2.Department of Oral Pathology, Hospital of Stomatology, Jilin University, Changchun 130021, China
3.Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun 130021, China
Funds：
DOI：10.1631/jzus.B2300779
CLC：
CSTR：
Received：29 October 2023，

Revised：12 January 2024，

Published Online：23 April 2025，

Published：23 April 2025
Accepted：

周怡君,史册,孙宏晨.进行性骨化性纤维发育不良的发病机制及药物治疗的研究进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(04):317-332.

Yijun ZHOU, Ce SHI, Hongchen SUN. Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(4): 317-332.
周怡君,史册,孙宏晨.进行性骨化性纤维发育不良的发病机制及药物治疗的研究进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(04):317-332. DOI： 10.1631/jzus.B2300779.

Yijun ZHOU, Ce SHI, Hongchen SUN. Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(4): 317-332. DOI： 10.1631/jzus.B2300779.

摘要

进行性骨化性纤维发育不良（FOP）是一种罕见的遗传性疾病，它以先天性双侧大脚趾畸形和全身软组织进行性、广泛性和不可逆的异位骨化（HO）为特征，最终可导致严重残疾。FOP主要由活化素A受体1（ACVR1，也被称为活化素受体样激酶2，即ALK2）的突变引起，该受体属于骨形态发生蛋白（BMP）I型受体。然而，FOP中复杂的HO形成机制尚未完全明确，这阻碍了治疗药物的开发。手术切除骨化组织常会导致HO的复发和扩大，而目前尚无药物可完全预防、停止或逆转FOP中HO的进展。目前，研究人员正在深入研究各个阶段FOP的发病机制，并开发候选药物，包括saracatinib、palovarotene和rapamycin等。本文就FOP的发病机制及治疗药物的研究进展进行综述，以期为进一步研究和开发新的治疗方法提供参考。

Abstract

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 (

ACVR1

)

also known as activin-like kinase 2 (

ALK2

)

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.

关键词

Keywords

references

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