{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Song IW"],"funding":["Brittle Bone Disorders Consortium","NICHD NIH HHS","The Clinical Translational Core of BCM IDDRC","NCI NIH HHS","NIAMS NIH HHS","USDA/ARS under Cooperative Agreement"],"pagination":["e152571"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8970679"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["132(7)"],"pubmed_abstract":["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 "],"journal":["The Journal of clinical investigation"],"pubmed_title":["Targeting TGF-β for treatment of osteogenesis imperfecta."],"pmcid":["PMC8970679"],"funding_grant_id":["58-6250-6-001","P50 HD103555","U54AR068069","U54 AR068069","P30 CA125123","P50HD103555"],"pubmed_authors":["Strudthoff E","Rosenfeld S","Orwoll E","Wallace M","McGuire S","Shenava V","Tran A","Munivez E","Shypailo R","Jiang MM","Lee B","Esposito P","Huang S","Thornton M","Song IW","Sutton VR","Nguyen D","Grafe I","Gannon FH","Musaad S","Nagamani SC"],"additional_accession":[]},"is_claimable":false,"name":"Targeting TGF-β for treatment of osteogenesis imperfecta.","description":"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 ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-31T01:04:52.123Z","creation":"2025-04-04T11:31:31.907Z"},"accession":"S-EPMC8970679","cross_references":{"pubmed":["35113812"],"doi":["10.1172/JCI152571"]}}