Compound KTI-2338 Inhibits ACVR1 Receptor Signaling in Fibrodysplasia Ossificans Progressiva.

ABSTRACT: Background/Objectives: Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic bone disorder, leading to progressive immobilization through the formation of bone in muscles, tendons, and ligaments. A variant in the ACVR1 gene results in a constitutively overactive ALK2 receptor, leading to the aberrant activation of the SMAD1/5/9 pathway. This activation occurs not only in response to Activin A, which does not normally activate this pathway, but also through heightened sensitivity to BMP ligands and even in the absence of ligand binding. This dysregulated signaling ultimately drives the formation of heterotopic ossification. The inhibition of the altered ALK2 receptor holds promise as a potential treatment strategy that is currently being investigated in several trials.

SUBMITTER: Rosenberg NM 

PROVIDER: S-EPMC12736380 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature