Fibrodysplasia ossificans progressiva: A blueprint for metamorphosis

Frederick S. Kaplan, Vitali Y. Lounev, Haitao Wang, Robert J. Pignolo, Eileen M. Shore

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The most important milestone in understanding a genetic disease is the identification of the causative mutation. However, such knowledge is often insufficient to decipher the pathophysiology of the disorder or to effectively treat those affected. Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling, genetic disease of progressive heterotopic endochondral ossification (HEO) enabled by missense mutations that promiscuously and provisionally activate ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, in all affected individuals. While activating mutations of the ACVR1/ALK2 receptor are necessary, disease activity and progression also depend on altered cell and tissue physiology. Recent findings identify inflammatory and immunological factors, vascular-derived mesenchymal stem cells, and a hypoxic lesional microenvironment that trigger, promote, and enable episodic progression of FOP in the setting of the genetic mutation. Effective therapies for FOP will need to consider these seminal pathophysiologic interactions.

Original languageEnglish (US)
Pages (from-to)5-10
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume1237
Issue number1
DOIs
StatePublished - Nov 2011

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Keywords

  • ACVR1
  • ALK2
  • BMP
  • Fibrodysplasia
  • Heterotopic ossification
  • Ossificans progressiva

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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