Self-assembling peptides for regeneration and repair of neural tissue

Abstract

The present invention provides methods and compositions for enhancing regeneration and/or repair of neural tissue. One method include providing a nanoscale structured material at the site of injury, wherein the nanoscale structured material provides an environment that is permissive for regeneration of neural tissue and allows axon growth from a location on one side of a site of injury or barrier to a location on the other side of the site of injury or barrier. A second method includes introducing a composition comprising self-assembling peptides into the subject at the site of injury, wherein the peptides are amphiphilic peptides that comprise substantially equal proportions of hydrophobic and hydrophilic amino acids and are complementary and structurally compatible. A variety of compositions comprising a nanoscale structured material or precursor thereof, and an additional substance such as a regeneration promoting factor, are also provided. In certain embodiments of the invention the nanoscale structured material or precursor thereof comprises self-assembling peptides. The invention further provides compositions and methods for repair of an intervertebral disc, including nucleus pulpusos repair.

1 - 5 . (canceled) 
     
     
         6 . A method for treating a subject with a neuronal injury comprising:
 introducing to the subject, at the site of the neuronal injury, a composition comprising a plurality of peptides, the peptides comprising between 8 and 16 amino acids,   wherein the peptides are amphiphilic and comprise substantially equal proportions of alternating hydrophobic and hydrophilic amino acids and are complementary and structurally compatible.   
     
     
         7 - 55 . (canceled) 
     
     
         56 . A method for treating a subject with spinal dysfunction or damage comprising:
 introducing to the subject, at the site of the spinal dysfunction, a composition comprising a plurality of peptides, the peptides comprising between 8 and 16 amino acids,   wherein the peptides are amphiphilic and comprise substantially equal proportions of alternating hydrophobic and hydrophilic amino acids that are complementary and structurally compatible.   
     
     
         72 . The method of  claim 6 , wherein each peptide has an amino acid sequence that includes at least one instance of RADA. 
     
     
         73 . The method of  claim 6 , wherein each peptide has an amino acid sequence that includes at least one instance of RADA16 (SEQ ID NO. 1). 
     
     
         74 . The method of  claim 6 , further comprising the step of assembling the peptides in situ. 
     
     
         75 . The method of  claim 74 , further comprising the step of adding ions to the composition to induce assembly. 
     
     
         76 . The method of  claim 6 , wherein the peptides are self-assembled prior to the introducing step. 
     
     
         77 . The method of  claim 6 , wherein the peptides are self-assembled during the introducing step. 
     
     
         78 . The method of  claim 6 , wherein the composition is in solution. 
     
     
         79 . The method of  claim 78 , wherein the composition has a peptide concentration between about 0.1 percent (1 mg/ml) and about 10 percent (100 mg/ml). 
     
     
         80 . The method of  claim 79 , wherein the composition has a peptide concentration between about 0.5 percent (5 mg/ml) and about 5 percent (50 mg/ml). 
     
     
         81 . The method of  claim 79 , wherein the composition has a peptide concentration of about 1 mg/ml, about 5 mg/ml, about 10 mg/ml, about 15 mg/ml, about 20 mg/ml or about 25 mg/ml. 
     
     
         82 . The method of  claim 6 , wherein the introducing step is by injection. 
     
     
         83 . The method of  claim 6 , wherein the site of the neuronal injury is in the central nervous system. 
     
     
         84 . The method of  claim 6 , wherein the site of the neuronal injury is in the peripheral nervous system. 
     
     
         85 . The method of  claim 6 , wherein the composition comprises a regeneration promoting factor. 
     
     
         86 . The method of  claim 85 , wherein the regeneration promoting factor is selected from the group consisting of: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (Nt-4/5), ciliary neurotrophic factor (CNTF), glial cell derived growth factor (GDNF), neurturin (NTN), persephin (PSP), artemin (ART), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), growth-associated protein 43 (GAP-43), cytoskeleton-associated protein 23 (CAP-23), B-cell lymphoma 2 (Bcl-2), L1, neural cell adhesion molecule (NCAM), N-cadherin, agrin, laminin, acetylcholine receptor inducing activity protein (ARIA), a semaphorin, a slit protein, a netrin, and an ephrin. 
     
     
         87 . The method of claim  1 , wherein the composition comprises an siRNA, shRNA, or a template for synthesis of an siRNA or shRNA that is targeted to a transcript that encodes the molecule that inhibits regeneration or repair. 
     
     
         88 . A method for preventing the formation of scar tissue in nerve tissue in a subject comprising:
 introducing to the subject, at the site of the nerve tissue, a composition comprising a plurality of peptides, the peptides comprising between 8 and 16 amino acids,   wherein the peptides are amphiphilic and comprise substantially equal proportions of alternating hydrophobic and hydrophilic amino acids that are complementary and structurally compatible.