When One Skeleton is Enough: Approaches and Strategies for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)

Overview

Journal Drug Discov Today Ther Strateg

Publisher Elsevier

Date 2013 Apr 20

PMID 23599718

Citations 12

Authors

Frederick S Kaplan

Jay Groppe

Eileen M Shore

Affiliations

Soon will be listed here.

Abstract

A heterozygous missense mutation in activin receptor IA/activin-like kinase-2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, is responsible for fibrodysplasia ossificans progressiva (FOP), the most catastrophic disorder of skeletal metamorphosis in humans. The discovery of the FOP gene establishes a crucial milestone in understanding FOP, reveals a highly conserved target in the BMP signaling pathway for drug development and specifically stimulates therapeutic approaches for the development of inhibitors for ACVR1/ALK2 signaling. Effective therapies for FOP, and possibly for more common conditions of heterotopic ossification, will be based on interventions that selectively block promiscuous ACVR1/ALK2 signaling, and/or themolecular triggers, responding cells and tissue microenvironments that facilitate aberrant skeletal metamorphosis in a permissive genetic background of increased BMP pathway activity.

Citing Articles

The role of Activin A in fibrodysplasia ossificans progressiva: a prominent mediator.

Lin H, Shi F, Gao J, Hua P Biosci Rep. 2019; 39(8).

PMID: 31341010 PMC: 6680371. DOI: 10.1042/BSR20190377.

Difficult diagnosis and genetic analysis of fibrodysplasia ossificans progressiva: a case report.

Tian S, Zhu J, Lu Y BMC Med Genet. 2018; 19(1):30.

PMID: 29482508 PMC: 5828422. DOI: 10.1186/s12881-018-0543-7.

Myositis ossificans in children: a review.

Sferopoulos N, Kotakidou R, Petropoulos A Eur J Orthop Surg Traumatol. 2017; 27(4):491-502.

PMID: 28275867 DOI: 10.1007/s00590-017-1932-x.

TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation.

Rahman M, Akhtar N, Jamil H, Banik R, Asaduzzaman S Bone Res. 2015; 3:15005.

PMID: 26273537 PMC: 4472151. DOI: 10.1038/boneres.2015.5.

Cellular and morphological aspects of fibrodysplasia ossificans progressiva. Lessons of formation, repair, and bone bioengineering.

Martelli A, Santos Jr A Organogenesis. 2014; 10(3):303-11.

PMID: 25482313 PMC: 4750545. DOI: 10.4161/org.29206.

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