biostudies-literatureSong IWBrittle Bone Disorders ConsortiumNICHD NIH HHSThe Clinical Translational Core of BCM IDDRCNCI NIH HHSNIAMS NIH HHSUSDA/ARS under Cooperative Agreemente152571https://www.ebi.ac.uk/biostudies/studies/S-EPMC8970679biostudies-literatureUnknown132(7)BACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-β signaling is a pathogenic mechanism in OI. Here, we evaluated TGF-β signaling in children with OI and conducted a phase I clinical trial of TGF-β inhibition in adults with OI.METHODSHistology and RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) were used to identify dysregulated pathways. Reverse-phase protein array, Western blot, and IHC were performed to evaluate protein expression. A phase I study of fresolimumab, a TGF-β neutralizing antibody, was conducted in 8 adults with OI. Safety and effects on bone remodeling markers and The Journal of clinical investigationTargeting TGF-β for treatment of osteogenesis imperfecta.PMC897067958-6250-6-001P50 HD103555U54AR068069U54 AR068069P30 CA125123P50HD103555Strudthoff ERosenfeld SOrwoll EWallace MMcGuire SShenava VTran AMunivez EShypailo RJiang MMLee BEsposito PHuang SThornton MSong IWSutton VRNguyen DGrafe IGannon FHMusaad SNagamani SCfalseTargeting TGF-β for treatment of osteogenesis imperfecta.BACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-β signaling is a pathogenic mechanism in OI. Here, we evaluated TGF-β signaling in children with OI and conducted a phase I clinical trial of TGF-β inhibition in adults with OI.METHODSHistology and RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) were used to identify dysregulated pathways. Reverse-phase protein array, Western blot, and IHC were performed to evaluate protein expression. A phase I study of fresolimumab, a TGF-β neutralizing antibody, was conducted in 8 adults with OI. Safety and effects on bone remodeling markers and 2022-01-01T00:00:00Z2022 Apr2026-05-31T01:04:52.123Z2025-04-04T11:31:31.907ZS-EPMC89706793511381210.1172/JCI152571