A setback in the use of monoclonal antibodies in FOP

Fibrodysplasia ossificans progessiva (FOP) is an ultra-rare disease caused by a mutation, almost always identical, in the ACVR1 gene. This gene encodes a type I bone morphogenetic protein (BMP) receptor. The clinical picture includes outbreaks of heterotopic ossification in the muscles, leading to true ankylosis.

  • Among the many therapeutic avenues considered, the specific blocking of the receptor ligand seemed very attractive;
  • however, two independent groups of researchers have just demonstrated that the use of these monoclonal antibodies is deleterious, at least in animals;
  • the FOP model animals used for this purpose tended to develop more heterotopic ossification, the opposite of what was expected.


ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1. Aykul S, Huang L, Wang L et al. J Clin Invest. 2022 May 5:e153792.


An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice. Lees-Shepard JB, Stoessel SJ, Chandler JT et al. J Clin Invest. 2022 May 3:e153795.