Tissue repair by modulation of beta-1 integrin biological function

摘要

The present invention methods and novel compounds for facilitating tissue repair and regeneration when the extracellular matrix is damaged. Specifically, binding of the beta 1 integrin is shown to provide a modulation of its functional activity resulting in up regulation of extracellular matrix anabolism. The invention therefore provides a method and novel compounds which can facilitate tissue regeneration in many systems such as the lung, skin, liver and bone. In particular, the binding of the JB1a antibody to a site of amino acid residues 82 to 87 of the mature beta 1 integrin is shown to be particularly effective in mediating the described tissue repair effect.

主权项

1. A method of enhancing tissue repair and regeneration to treat emphysema comprising administering an antibody, or an antigen binding fragment thereof, which modulates function of beta 1 integrin to a subject in need thereof, wherein the antibody or an antigen binding fragment binds to a domain of beta 1 integrin comprising amino acid residues 82 to 87 comprising residues TAEKLK (SEQ ID NO: 1) of mature beta 1 integrin and wherein the functional modulation of beta 1 integrin results in (i) an inhibition of apoptotic pathway, (ii) an alteration in metalloproteinases, (iii) an increase in an anabolism of extracellular matrix and (iv) an increase in inactive-MMP9.