University of Utah Research Foundation

La Jolla Cancer Research Foundation

The Burnham Institute

American National Red Cross

Wayne A Border

Nancy A Noble

Erkki I Ruoslahti

Daniel Lawrence

Yu Yamaguchi

The present invention is methods and compositions for reducing and preventing the excess accumulation of extracellular matrix in a tissue and/or organ or at a wound site using a combination of agents that inhibit TGF&#x3b2;, or using agents that inhibit TGF&#x3b2; in combination with agents that degrade excess accumulated extracellular matrix, or at least one agent that degrades excess accumulated extracellular matrix. The compositions and methods of the invention are used to treat conditions such as fibrotic diseases and scarring that result from excess accumulation of extracellular matrix, impairing tissue or organ function or skin appearance in a subject.

Methods for treating conditions associated with the accumulation of excess extracellular matrix

The present invention is methods and compositions for reducing and preventing the excess accumulation of extracellular matrix in a tissue and/or organ or at a wound site using a combination of agents that inhibit TGF&#x3b2;, or using agents that inhibit TGF&#x3b2; in combination with agents that degrade excess accumulated extracellular matrix. The compositions and methods of the invention are used to treat conditions such as fibrotic diseases and scarring that result from excess accumulation of extracellular matrix, impairing tissue or organ function or skin appearance in a subject.

The present invention provides a method for treating or arresting the progress of pathologies characterized by an accumulation of extracellular matrix components by providing an agent to suppress the activity of transforming growth factor &#x3b2; (TGF-&#x3b2;) a peptide growth factor which is anabolic and leads to fibrosis and angiogenesis. In one embodiment, such agent is anti-TGF-&#x3b2; antibody. Pathologies which can be so treated include, but are not limited to, glomerulonephritis, adult respiratory distress syndrome and cirrhosis of the liver. The invention further provides a method for the diagnosis of pathologies, or incipient pathologies, which are characterized by the accumulation of extracellular matrix components in tissues by determining the levels of TGF-&#x3b2; in the tissues, a high level being indicative of such pathologies.

Methods of decreasing the accumulation of extracellular matrix associated with glomerulonephritis with anti-TGF-&#x3b2;-specific antibodies

The present invention relates to methods of preventing or reducing scarring in a wound area by administering decorin or biglycan to the wound.

Methods of preventing or reducing scarring with decorin or biglycan

The present invention is methods for inhibiting the renin-induced production of TGF&bgr; using a renin inhibitory agent to reduce excess accumulation of extracellular matrix in tissue in a subject, and to the use of renin inhibitory agents and additional TGF&bgr; inhibitory agents to reduce TGF&bgr; production to treat and prevent fibrotic diseases.

Methods for preventing and treating fibrotic diseases resulting from accumulation of excess extracellular matrix induced by TGF&bgr; using renin inhibitors

The present invention provides methods for reducing a pathology in a subject characterized by a deleterious accumulation of TGF-.beta.-induced extracellular matrix in a tissue by introducing a nucleic acid encoding a TGF.beta.-specific inhibitory agent or active fragment thereof into a cell in the subject. In one embodiment, the nucleic acid encoding the TGF-.beta. specific inhibitory agent is introduced into a cell in vivo by injection, for example, in skeletal muscle. In another embodiment, the nucleic acid encoding the TGF-.beta. specific inhibitory agent is transfected into a cell ex vivo to obtain a cell expressing the agent, and the cell is then administered into the subject to be treated. TGF-.beta. specific inhibitory agents of the present invention include, but are not limited to, members of the decoring family of proteoglycans such as decorin, biglycan, fibromodulin and lumican or an antibody specific for TGF-.beta.. Pathologies that can be reduced by the present invention include various fibrotic diseases and conditions.

Anti-transforming growth factor-.beta. gene therapy

A method of treating of glomerulonephritis in a patient by administering decorin.

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Salt Lake City, UT, United States of America

Wayne A Border