adenovirus tissue inhibitor of matrix metalloproteinase-3

Adenovirus tissue inhibitor of matrix metalloproteinase-3 (also known as Ad5.CMVTO.TIMP-3 or RAdTIMP-3) is an investigational gene therapy designed to prevent saphenous vein graft (SVG) failure following coronary artery bypass graft (CABG) surgery. Developed by NHS Greater Glasgow and Clyde in collaboration with the University of Glasgow, the therapy consists of a replication-deficient recombinant adenoviral vector engineered to overexpress the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) gene. TIMP-3 is an endogenous extracellular matrix-associated inhibitor of matrix metalloproteinases (MMPs). By overexpressing TIMP-3, the therapy inhibits MMP-driven cell migration, stabilizes the extracellular matrix, and promotes vascular smooth muscle cell (VSMC) apoptosis via a FAS-dependent death receptor pathway, thereby preventing neointimal hyperplasia and subsequent graft occlusion. The treatment is administered ex vivo, where harvested vein graft segments are exposed to the gene therapy for 30 minutes prior to surgical implantation.

Other names

adenovirus tissue inhibitor of metalloproteinase-3adenoviral TIMP-3adenoviral tissue inhibitor of metalloproteinase-3