Regenerative Polypeptides and Uses Thereof

Abstract

Described herein are polypeptides comprising an FGF17, IGF2, or BMP7 amino acid sequence and an amino acid sequence from a heterologous polypeptide useful for the treatment of soft-tissue and muscle diseases, disorders, and injuries. Also described herein are synergistic combinations of a Fibroblast Growth Factor Receptor agonist and a glycosaminoglycan, an Insulin-like Growth Factor 1 Receptor (IGF1R) agonist and a short chain fatty acid, and BMP receptor agonists and mTOR activators and/or glycosaminoglycans. Also described are methods of treating muscle and soft-tissue diseases comprising administering the polypeptides and/or synergistic compositions.

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         26 . A method of treating an individual with a cartilage-related disorder comprising administering a therapeutically effective amount of a polypeptide comprising a Fibroblast Growth Factor 17 (FGF17) subfamily amino acid sequence to the individual. 
     
     
         27 . The method of  claim 26 , wherein the FGF17 amino acid sequence comprises an amino acid sequence at least about 90%, 95%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 54. 
     
     
         28 . The method of  claim 27 , wherein the FGF17 amino acid sequence further comprises a mutation selected from: deletion of amino acids G181-T203, deletion of amino acids 197-T203, deletion of amino acids 204-216, deletion of amino acids 181-216, amino acid substitutions R204Q and K207Q, deletion of amino acids 197-216, amino acid substitutions K191A, K193A, and S200A, and combinations thereof. 
     
     
         29 . The method of  claim 26 , wherein proliferation of a chondrocyte is increased. 
     
     
         30 . The method of  claim 26 , wherein the FGF17 promotes survival of a chondrocyte. 
     
     
         31 . The method of  claim 26 , wherein the FGF17 reduces senescence of a chondrocyte. 
     
     
         32 . The method of  claim 26 , wherein the FGF17 increases expression of a SOX9, a MMP3, a MMP13, or a COL2A1. 
     
     
         33 . The method of  claim 26 , wherein the cartilage-related disorder is an osteoarthritis, an osteochondritis dissecans, an achondroplasia, or a degenerative cartilage lesion. 
     
     
         34 . The method of  claim 29 , wherein the cartilage related disorder is an osteoarthritis. 
     
     
         35 . The method of  claim 26 , wherein the cartilage-related disorder may be due to tears, injuries, or wear. 
     
     
         36 . The method of  claim 26 , wherein the cartilage-related disorder is a cartilage damage. 
     
     
         37 . The method of  claim 25 , wherein the cartilage-related disorder is a cartilage loss. 
     
     
         38 . The method of  claim 34 , wherein proliferation of a chondrocyte is increased. 
     
     
         39 . The method of  claim 38 , wherein the FGF17 promotes survival of a chondrocyte. 
     
     
         40 . The method of  claim 39 , wherein the FGF17 reduces senescence of a chondrocyte. 
     
     
         41 . The method of  claim 40 , wherein the FGF17 increases expression of a SOX9, a MMP3, a MMP13, or a COL2A1. 
     
     
         42 . The method of  claim 26 , wherein the polypeptide further comprises a modification to improve stability. 
     
     
         43 . The method of  claim 42 , wherein the modification is a chemical medication. 
     
     
         44 . The method of  claim 42 , wherein the modification is a conjugation to another protein. 
     
     
         45 . The method of  claim 44 , further comprising the amino acid substitutions K191A, K193A, and S200A in the FGF17, and the other protein is a human Fcm.