Polypeptide compositions with type vii collagen fibronectin type iii-like repeats and treatment methods for wound closure and healing

Abstract

Disclosed are compositions arid methods for accelerating wound closure and preventing inhibiting or reducing scarring or fibrosis. The methods of the present invention include administering to a person in need thereof an effective amount of a pharmaceutical composition comprising collagen 7 and/or one: or snore functional fragments or variants thereof. The functional fragments generally comprise at last one of the nine Fibronectin Type III-like Region of the NC1 region of collagen 7.

What is claimed is: 
     
         1 . A method of accelerating wound healing in a subject, the method comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition, the pharmaceutical composition comprising:
 a) one or more functional fragments of collagen 7; and   b) a pharmaceutical carrier.   
     
     
         2 . The method of  claim 1 , wherein the subject has no mutation in the COL7A1 gene. 
     
     
         3 . The method of  claim 1 , wherein the pharmaceutical composition is administered topically. 
     
     
         4 . The method of  claim 1 , wherein collagen 7 has an amino acid sequence as set forth in SEQ ID NO:1. 
     
     
         5 . The method of  claim 4 , wherein the one or more functional fragments is selected from the group consisting of FNIII Region 1 having an amino acid sequence corresponding to amino acid residues 233 to 325 of SEQ ID NO:1, FNIII Region 2 having an amino acid sequence corresponding to amino acid residues 333 to 413 of SEQ ID NO:1, FNIII Region 3 having an amino acid sequence corresponding to amino acid residues 419 to 492 of SEQ ID NO:1, FNIII Region 4 having an amino acid sequence corresponding to amino acid residues 509 to 587 of SEQ ID NO:1, FNIII Region 5 having an amino acid sequence corresponding to amino acid residues 598 to 680 of SEQ ID NO:1, FNIII Region 6 having an amino acid sequence corresponding to amino acid residues 687 to 771 of SEQ ID NO:1, FNIII Region 7 having an amino acid sequence corresponding to amino acid residues 777 to 862 of SEQ ID NO:1, FNIII Region 8 having an amino acid sequence corresponding to amino acid residues 867 to 952 of SEQ ID NO:1, FNIII Region 9 having an amino acid sequence corresponding to amino acid residues 955 to 1044 of SEQ ID NO:1, PCR2 having an amino acid sequence corresponding to amino acid residues 596 to 826 of SEQ ID NO:1, PCR3 having an amino acid sequence corresponding to amino acid residues 202 to 602 of SEQ ID NO:1, FP15 having an amino acid sequence corresponding to amino acid residues 596 to 709 of SEQ ID NO:1, FP16 having an amino acid sequence corresponding to amino acid residues 707 to 826 of SEQ ID NO:1, and PpuMi having an amino acid sequence corresponding to amino acid residues 202 to 360 of SEQ ID NO:1. 
     
     
         6 . The method of  claim 1 , wherein the one or more functional fragments is not capable of forming anchoring fibrils between the epidermal and dermal layers of human skin but is capable of binding to TGF-β1 and inhibiting TGF-β1 and TGF-β2 activity. 
     
     
         7 . The method of  claim 1 , wherein the one or more functional fragments is selected from the group consisting of FNIII Region 1, FNIII Region 2, FNIII Region 3, FNIII Region 4, FNIII Region 5, FNIII Region 6, FNIII Region 7, FNIII Region 8, and FNIII Region 9. 
     
     
         8 . The method of  claim 7 , wherein the one or more functional fragments comprises an amino acid sequence corresponding to residues 17 to 1253 of SEQ ID NO:1. 
     
     
         9 . The method of  claim 8 , wherein the one or more functional fragments further comprises an amino acid sequence corresponding to a fragment of less than 100, 50, 40, 20 or 10 amino acid residues of the central collagenous helical domain and/or less than 40, 20 or 10 amino acid residues of the carboxy terminal NC2 domain. 
     
     
         10 . The method of  claim 5 , wherein the one or more functional fragments is FNIII Region 1. 
     
     
         11 . The method of  claim 5 , wherein the one or more functional fragments is FNIII Region 5. 
     
     
         12 . The method of  claim 5 , wherein the one or more functional fragments is FNIII Region 6. 
     
     
         13 . The method of  claim 5 , wherein the one or more functional fragments is PCR2. 
     
     
         14 . The method of  claim 5 , wherein the one or more functional fragments is PCR3. 
     
     
         15 . The method of  claim 5 , wherein the one or more functional fragments is FP15. 
     
     
         16 . The method of  claim 5 , wherein the one or more functional fragments is FP16. 
     
     
         17 . The method of  claim 1 , wherein the one or more functional fragments includes an amino acid sequence that correspond to the binding site of collagen 7 to TGF-β1 and/or TGF-β2.