™™| 09/06/10 | |||
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Technology name:
Technology description: Membrane-type 1 matrix metalloprotein (MT1-MMP) has been identified as a target for treating age-related macular degeneration (AMD) and other retinal degenerations. MT-MMP activates pro-gelatinase A (proMMP 2), a major metalloproteinase responsible for cleavage of type IV collagen, the major structural component of basement membranes. MT1-MMP also has activity against other extracelluar matrix components, including type 1 and II collagen, fibronecting, vitronectin, laminin and proteoglycan.
Evidence for the role of MT1-MMP
• MT1-MMP is up-regulated
o In the retinal pigment epithelium (RPE) and photoreceptors of the eyes of patients with AMD
o In a monkey model of AMD
o In RCS rat, a model of retinal degeneration
• MT1-MMP is directly involved in the mechanism of phagocytosis by RPE Cells
• Progression of retinal degeneration in the RCS rat model is significantly reduced by blocking MT1-MMP action with an anti-MT1-MMP antibody
• A missense polymorphism of MT1-MMP, affecting the catalytic domain of the protein is found in higher frequency in DNA of patients with AMD
o 30% versus 14% | |||