From mysteries to medicines: Drug development for fibrodysplasia ossificans progressiva

Frederick S. Kaplan, Robert J. Pignolo, Eileen M. Shore

Research output: Contribution to journalReview article

25 Scopus citations

Abstract

Introduction: Fibrodysplasia ossificans progressiva (FOP) is the most disabling disorder of skeletal metamorphosis in humans and leads to the formation of a second skeleton of heterotopic bone. Presently, there is no effective treatment. Areas covered: In this review, the authors discuss heterozygous activating mutations in Activin receptor A, type I/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that are the genetic cause of FOP and reveal a promising pharmacologic target in the BMP signaling pathway. Despite these germline mutations, episodic disease activation is induced by soft tissue injury and resultant inflammatory triggers that are dependent on responding progenitor cells and a tissue microenvironment that supports heterotopic ossification. Expert opinion: Here, we review opportunities and challenges for the development of effective therapeutics for FOP. There are many potential approaches that may eventually be used to harness FOP. The long-term treatment of FOP is likely to involve not one, but several concomitant approaches that acknowledge molecular mechanisms involved in the induction and progression of the disease.

Original languageEnglish (US)
Pages (from-to)637-649
Number of pages13
JournalExpert Opinion on Orphan Drugs
Volume1
Issue number8
DOIs
StatePublished - 2013

Keywords

  • Bone morphogenetic protein receptors
  • Fibrodysplasia ossificans progressiva
  • Heterotopic endochondral ossification
  • Skeletal metamorphosis

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
  • Health Policy
  • Pharmacology (medical)

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