The Role of ACVR1 in the Pathogenesis of Fibrodysplasia Ossificans Progressiva

Abstract

Fibrodysplasia Ossificans Progressiva (FOP) is a rare and severely disabling genetic disorder characterized by progressive heterotopic ossification, where bone forms in soft tissues outside the normal skeletal structure. This pathological process leads to severe immobility and a drastically reduced quality of life. The disorder is primarily caused by a recurrent activating mutation in the ACVR1 gene, which encodes a bone morphogenetic protein (BMP) type I receptor. The most common mutation, R206H, results in constitutive activation of the BMP signaling pathway, driving abnormal bone formation. This review delves into the role of ACVR1 in FOP pathogenesis, detailing the molecular mechanisms by which the R206H mutation disrupts BMP signaling and triggers heterotopic ossification. Additionally, it examines the progression of the disease, challenges in developing effective treatments, and emerging therapeutic strategies, including targeted approaches to inhibit the overactive ACVR1 receptor. These insights provide a foundation for advancing the understanding and management of FOP.