An ultra-rare disease, fibrodysplasia ossificans progressiva (FOP) results from gain-of-function mutations in the ACVR1 or ALK2 gene, which lead to the formation of heterotopic ossifications. Preclinical results (particularly in mouse models) published in June 2025 show that these ossifications are prevented by oral administration of:
- RK783, a molecule identified during the screening of 140,000 molecules that selectively inhibits the BMP-Smad1/5/9 signaling pathway, which is abnormally activated in FOP,
- BYL719 or alpelisib, or Piqray®, an anticancer drug that inhibits phosphatidylinositol -3-kinase (PI3Kα).
The first compound is thought to be more effective at high doses and when administered acutely, within two days of muscle trauma. Alpelisib remains effective when administered three to seven days after the same trauma.
