Morphogen-induced modulation of inflammatory response

Abstract

The present invention is directed to methods and compositions for alleviating tissue destructive effects associated with the inflammatory response to tissue injury in a mammal. The methods and compositions include administering a therapeutically effective concentration of a morphogen or morphogen-stimulating agent sufficient to alleviate immune cell-mediated tissue destruction.

1 - 48 . (canceled)  
     
     
         49 . A method for enhancing recovery of central nervous system function in a mammal, comprising administering an effective amount of a morphogen to a mammal afflicted with a central nervous system injury selected from ischemia or trauma, wherein said morphogen induces tissue-specific morphogenesis in said mammal and comprises a pair of folded polypeptides, each having an amino acid sequence having at least 70% homology with or 60% identity to the C-terminal seven-cysteine domain of human OP-1, residues 38-139 of SEQ ID NO: 5.  
     
     
         50 . A method for enhancing recovery of central nervous system function in a mammal, comprising administering an effective amount of a morphogen to a mammal afflicted with a central nervous system injury selected from ischemia or trauma, wherein said morphogen induces tissue-specific morphogenesis in said mammal and comprises a pair of folded polypeptides, each having an amino acid sequence selected from: 
 (a) Generic Sequence 3 defined by SEQ ID NO: 3;    (b) Generic Sequence 4 defined by SEQ ID NO: 4;    (c) Generic Sequence 5 defined by SEQ ID NO: 30; or,    (d) Generic Sequence 6 defined by SEQ ID NO: 31.    
     
     
         51 . A method for enhancing recovery of central nervous system function in a mammal, comprising administering an effective amount of a morphogen to a mammal afflicted with a central nervous system injury selected from ischemia or trauma, wherein said morphogen is human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP-2A, BMP-2B, DPP, Vgl, Vgr-1, BMP-3, BMP-5, or BMP-6.  
     
     
         52 . The method  claim 49 , wherein said amino acid sequence is that of the C-terminal seven-cysteine domain of human OP-1, residues 38-139 of SEQ ID NO: 5.  
     
     
         53 . The method of  claim 49 , wherein said morphogen is complexed with at least one pro-domain peptide comprising an N-terminal 18 amino acid peptide selected from N-termini of the pro domains of OP-1, OP-2, 60A, GDF-1, BMP-2A, BMP-2B, DPP, Vgl, Vgr-1, BMP-3, BMP-5, or BMP-6.  
     
     
         54 . The method  claim 49 , wherein said morphogen is noncovalently complexed with at least one solubility-enhancing fragment of a pro-domain polypeptide selected from the pro-domains of naturally-occurring morphogens.  
     
     
         55 . The method of  claim 54 , wherein said morphogen is complexed with a pair of said fragments.  
     
     
         56 . The method of  claim 49 , wherein said morphogen comprises the amino acid sequence of SEQ ID NO: 5.