How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva.

ABSTRACT: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodic yet cumulative heterotopic ossification (HO) of skeletal muscles, tendons, ligaments, and fascia. FOP arises from missense mutations in Activin Receptor type I (ACVR1), a type I bone morphogenetic protein (BMP) receptor. Although initial findings implicated constitutive activity of FOP-variant ACVR1 (ACVR1^FOP) and/or hyperactivation by BMPs, it was later shown that HO in FOP requires activation of ACVR1^FOP by Activin A. Inhibition of Activin A completely prevents HO in FOP mice, indicating that Activin A is an obligate driver of HO in FOP, and excluding a key role for BMPs in this process. This discovery led to the clinical development of garetosmab, an investigational ant

SUBMITTER: Srinivasan D 

PROVIDER: S-EPMC10813747 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature