Proteoglycan degrading mutants for treatment of cns

Abstract

The present disclosure relates to the preparation and deletion mutants of chondroitinase proteins and their use in methods for promoting the diffusion of therapeutic composition into tissues and their use for neurological functional recovery after central nervous system (“CNS”) injury or disease.

What is claimed is: 
     
         1 . A mutant chondroitinase AC protein comprising an amino acid sequence of chondroitinase AC (SEQ ID NO: 5) truncated by a deletion of about 1 to about 100 amino acids from the N-terminus. 
     
     
         2 . The mutant chondroitinase AC protein of  claim 1 , further comprising a deletion of about 1 to about 275 amino acids from the C-terminus of chondroitinase AC (SEQ ID NO: 5). 
     
     
         3 . The mutant chondroitinae AC protein of  claim 2 , wherein the mutant chondroitinase AC protein is selected from SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11. 
     
     
         4 . A composition comprising a mutant chondroitinase AC protein comprising an amino acid sequence of chondroitinase AC (SEQ ID NO: 5) truncated by a deletion of about 1 to about 100 amino acids from the N-terminus. 
     
     
         5 . The composition of  claim 4 , wherein the mutant chondroitinase AC protein further comprises a deletion of about 1 to about 275 amino acids from the C-terminus of chondroitinase AC (SEQ ID NO: 5). 
     
     
         6 . The composition of  claim 5 , wherein the mutant chondroitinase AC protein is selected from SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11. 
     
     
         7 . The composition of  claim 5 , wherein the composition further comprises molecules that block action of neurite growth inhibitors, molecules that promote neurite growth, neurotrophic factors, neuregulins, neural cell adhesion molecule L1, growth factors, phosphodiesterase inhibitors, diagnostic molecules, therapeutic molecules, or a combination thereof. 
     
     
         8 . The composition of  claim 5 , further comprising a pharmaceutically acceptable excipient. 
     
     
         9 . A recombinant nucleic acid comprising a sequence encoding a mutant chondroitinase AC protein, wherein the mutant chondroitinase AC protein comprises an amino acid sequence of SEQ ID NO: 5 truncated by a deletion of about 1 to about 100 amino acids from the N-terminus.