Silencing the FOP gene

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease in which bone is formed in soft tissues through heterotopic ossification (HO). HO is often a problem for patients who have received a traumatic insult, either to musculoskeletal tissues (traumatic HO) or to the skin or spinal cord (neurologic HO). Although trauma-induced HO can be painful, it is often transitory and easily treated with conventional therapies such as bisphosphonates, radiation and surgical removal of the heterotopic bone. In sharp contrast, the unpredictable and progressive nature of FOP leads to severe impairment of mobility and eventual paralysis due to ossification of joints. In addition, as this form of HO characteristically occurs on the chest, back and spine, damage to internal organs, particularly compression of the lungs, contributes to the lethality of FOP. There is currently no treatment for FOP, due in part to the rarity of the disease and the difficulty in obtaining samples from FOP patients for study – even minimal trauma, such as a tissue biopsy, can trigger HO to occur in these patients. Thus, the discovery of the genetic mechanism of FOP in 2006 was a tremendous accomplishment and renewed the hope of finding a cure.1