Fibrodysplasia ossificans progressiva

Frederick S. Kaplan, Martine Le Merrer, David L. Glaser, Robert Pignolo, Robert E. Goldsby, Joseph A. Kitterman, Jay Groppe, Eileen M. Shore

Research output: Contribution to journalReview article

178 Citations (Scopus)

Abstract

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 IA/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)-β/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.

Original languageEnglish (US)
Pages (from-to)191-205
Number of pages15
JournalBest Practice and Research: Clinical Rheumatology
Volume22
Issue number1
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Myositis Ossificans
Heterotopic Ossification
Type I Bone Morphogenetic Protein Receptors
Activin Receptors
Soft Tissue Injuries
Activins
Mutation
Bone Morphogenetic Proteins
Transforming Growth Factors
Human Genome
Early Diagnosis
Signal Transduction
Phosphotransferases
Therapeutics
Pharmaceutical Preparations
Genes

Keywords

  • ACVR1
  • ALK2
  • BMP
  • bone morphogenetic protein
  • fibrodysplasia ossificans progressiva (FOP)
  • heterotopic ossification

ASJC Scopus subject areas

  • Rheumatology

Cite this

Kaplan, F. S., Le Merrer, M., Glaser, D. L., Pignolo, R., Goldsby, R. E., Kitterman, J. A., ... Shore, E. M. (2008). Fibrodysplasia ossificans progressiva. Best Practice and Research: Clinical Rheumatology, 22(1), 191-205. https://doi.org/10.1016/j.berh.2007.11.007

Fibrodysplasia ossificans progressiva. / Kaplan, Frederick S.; Le Merrer, Martine; Glaser, David L.; Pignolo, Robert; Goldsby, Robert E.; Kitterman, Joseph A.; Groppe, Jay; Shore, Eileen M.

In: Best Practice and Research: Clinical Rheumatology, Vol. 22, No. 1, 01.03.2008, p. 191-205.

Research output: Contribution to journalReview article

Kaplan, FS, Le Merrer, M, Glaser, DL, Pignolo, R, Goldsby, RE, Kitterman, JA, Groppe, J & Shore, EM 2008, 'Fibrodysplasia ossificans progressiva', Best Practice and Research: Clinical Rheumatology, vol. 22, no. 1, pp. 191-205. https://doi.org/10.1016/j.berh.2007.11.007
Kaplan FS, Le Merrer M, Glaser DL, Pignolo R, Goldsby RE, Kitterman JA et al. Fibrodysplasia ossificans progressiva. Best Practice and Research: Clinical Rheumatology. 2008 Mar 1;22(1):191-205. https://doi.org/10.1016/j.berh.2007.11.007
Kaplan, Frederick S. ; Le Merrer, Martine ; Glaser, David L. ; Pignolo, Robert ; Goldsby, Robert E. ; Kitterman, Joseph A. ; Groppe, Jay ; Shore, Eileen M. / Fibrodysplasia ossificans progressiva. In: Best Practice and Research: Clinical Rheumatology. 2008 ; Vol. 22, No. 1. pp. 191-205.
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