When one skeleton is enough: approaches and strategies for the treatment of fibrodysplasia ossificans progressiva (FOP)

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 the molecular triggers, responding cells and tissue microenvironments that facilitate aberrant skeletal metamorphosis in a permissive genetic background of increased BMP pathway activity.

Section editors:Frederick Kaplan – The University of Pennsylvania School of Medicine, Department of Orthopaedic Surgery, Philadelphia, PA 19104, USAAmber Salzman – Cardiokine, Inc., Philadelphia, PA 19102, USA