Methods for treatment of multiple sclerosis using peptide analogues at position 91 of human myelin basic protein

Abstract

Peptide analogues of human myelin basic protein containing residues 87-99 are provided. Residue 91 of the peptide analogues is altered from the L-lysine residue found in the native protein to any other amino acid. Pharmaceutical compositions of the peptide analogues are provided. In addition, the peptide analogues are administered to patients with multiple sclerosis.

What is claimed is:  
     
         1 . A peptide analogue derived from residues 87-99 of human myelin basic protein, wherein at least the lysine residue at position 91 is altered to another amino acid; and wherein the peptide analogue is not in the form of a noncovalent complex with a Major Histocompatibility (MHC) component.  
     
     
         2 . The peptide analogue of  claim 1  wherein the amino acid at position 91 is altered to a non-conservative amino acid.  
     
     
         3 . The peptide analogue of  claim 1  wherein the amino acid at position 91 is altered with an amino acid selected from the group consisting of D-lysine, alanine, glycine, glutamic acid, phenylalanine, arginine, asparagine, histidine, leucine and serine.  
     
     
         4 . The peptide analogue of  claim 1  wherein the amino acid at position 91 is altered to alanine.  
     
     
         5 . The peptide analogue of  claim 1  wherein the analogue causes reduced expression of TNF-α from MBP-reactive T cells relative to the native sequence.  
     
     
         6 . A pharmaceutical composition comprising a peptide analogue according to  claim 1  in combination with a physiologically acceptable carrier or diluent.  
     
     
         7 . A method of treating multiple sclerosis, comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising the peptide analogue of  claim 1 , in combination with a physiologically acceptable carrier or diluent.  
     
     
         8 . The method of  claim 7  wherein the amino acid at position 91 is altered with an amino acid selected from the group consisting of D-lysine, alanine, glycine, glutamic acid, phenylalanine, arginine, asparagine, histidine, leucine and serine.  
     
     
         9 . The method of  claim 7  wherein the amino acid at position 91 is altered to a non-conservative amino acid.  
     
     
         10 . The method of  claim 7  wherein the amino acid at position 91 is altered to alanine.  
     
     
         11 . The method of  claim 7  wherein the analogue causes reduced expression of TNF-α from MBP-reactive T cells relative to the native sequence.