Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Hum Gene Ther. 2022 Aug;33(15-16):782-788. doi: 10.1089/hum.2022.023.


Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

Keywords: ALK2 mutation; RNA; fibrodysplasia ossificans progressiva; gene therapy; heterotopic ossification.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Activin Receptors, Type I / genetics
  • Feasibility Studies
  • Genetic Therapy / adverse effects
  • Humans
  • Myositis Ossificans* / complications
  • Myositis Ossificans* / genetics
  • Myositis Ossificans* / therapy
  • Ossification, Heterotopic* / genetics


  • Activin Receptors, Type I