期刊
BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY
卷 22, 期 1, 页码 191-205出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.berh.2007.11.007
关键词
fibrodysplasia ossificans progressiva (FOP); heterotopic ossification; bone morphogenetic protein; BMP; ACVR1; ALK2
类别
资金
- NIAMS NIH HHS [R01 AR041916-07S1, R01 AR041916, R01 AR041916-11, R01 AR041916-07, R01 AR041916-09, R01 AR041916-10, R01 AR041916-06, R01 AR041916-08A1] Funding Source: Medline
Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic condition of congenital skeletal malformations and progressive heterotopic ossification (HO), is the most catastrophic disorder of HO in humans. Episodic disease flare-ups are precipitated by soft tissue injury, and immobility is cumulative. Recently, a recurrent mutation in activin receptor 1A/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, was reported in all sporadic and familial cases of classic FOP, making this one of the most highly specific disease-causing mutations in the human genome. The discovery of the FOP gene establishes a critical milestone in understanding FOP, reveals a highly conserved target for drug development in the transforming growth factor (TGF)-beta/BMP signalling pathway, and compels therapeutic approaches for the development of small molecule signal transduction inhibitors for ACVR1/ALK2. Present management involves early diagnosis, assiduous avoidance of iatrogenic harm, and symptomatic amelioration of painful flare-ups. Effective therapies for FOP, and possibly for other common conditions of HO, may potentially be based on future interventions that block ACVR1/ALK2 signalling.
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