Immune modulation for the treatment of age-related macular degeneration

Abstract

The invention provides methods for treating age-related macular degeneration by administering (i) peptide compositions, (ii) regulatory T-cells from the patient or a compatible donor, or (iii) a combination of regulatory T-cells and said peptide compositions. Also provided are methods for diagnosing age-related macular degeneration and monitoring its progression.

1 . A method for treating age-related macular degeneration (AMD) in a human patient, comprising the steps of:
 orally administering via ingestion to a human patient having age-related macular degeneration a therapeutically effective amount of a synthetic peptide 15 amino acids to 50 amino acids in length, said peptide comprising the sequence   VTVIWTNNTEKTVKK (SEQ ID NO: 3) or a variant thereof in which a single amino acid is substituted with a different amino acid; and   repeating the oral administration via ingestion step for a plurality of days.   
     
     
         2 . The method of  claim 1 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         3 . The method of  claim 1 , wherein the synthetic peptide is
 VTVDVTNNTEKTVKK (SEQ ID NO: 3) or a variant thereof in which a single amino acid is substituted with a different amino acid.   
     
     
         4 . The method of  claim 3 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         5 . The method of  claim 3 , wherein the synthetic peptide is 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 3) 
                 
                     
                   VTVDVTNNTEKTVKK. 
                 
             
                
                
               
            
           
         
       
     
     
         6 . The method of  claim 5 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         7 . The method of  claim 1 , wherein the synthetic peptide comprises the sequence
 GEPIPVTVDVTNNTEKTVKK (SEQ ID NO: 2 or a variant thereof in which one or two amino acids are substituted with a different amino acid.   
     
     
         8 . The method of  claim 7 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         9 . The method of  claim 7 , wherein the synthetic peptide is
 GEPIPVTVDVTNNTEKTVKK (SEQ ID NO: 2) or a variant thereof in which one or two amino acids are substituted with a different amino acid.   
     
     
         10 . The method of  claim 9 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         11 . The method of  claim 1 , further comprising the step of:
 co-administering to the human patient at least one enhancer selected from the group consisting of: high molecular weight hyaluronic acid; IL-2; IL-15; TGF-β; all-trans retinoic acid; rapamycin; anti-CD3; anti-CD28; vitamin D3; dexamethasone; IL-10; idolamine-2,3-dioxygenase; FTY720; a sphingosine kinase 1 inhibitor; cholera toxin B subunit; ovalbumin; Flt2L; sirolimus; anti-thymocyte globulin; and CTLA-4/Ig.   
     
     
         12 . The method of  claim 11 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         13 . The method of  claim 3 , further comprising the step of:
 co-administering to the human patient at least one enhancer selected from the group consisting of: high molecular weight hyaluronic acid; IL-2; IL-15; TGF-β; all-trans retinoic acid; rapamycin; anti-CD3; anti-CD28; vitamin D3; dexamethasone; IL-10; idolamine-2,3-dioxygenase; FTY720; a sphingosine kinase 1 inhibitor; cholera toxin B subunit; ovalbumin; Flt2L; sirolimus; anti-thymocyte globulin; and CTLA-4/Ig.   
     
     
         14 . The method of  claim 13 , wherein the at least one enhancer comprises high molecular weight hyaluronic acid. 
     
     
         15 . The method of  claim 13 , Wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         16 . The method of  claim 5 , further comprising the step of:
 co-administering to the human patient at least one enhancer selected from the group consisting of: high molecular weight hyaluronic acid; IL-2; IL-15; TGF-β; all-trans retinoic acid; rapamycin; anti-CD3; anti-CD28; vitamin D3; dexamethasone; IL-10; idolamine-2,3-dioxygenase; FTY720; a sphingosine kinase 1 inhibitor; cholera toxin B subunit; ovalbumin; Flt2L; sirolimus; anti-thymocyte globulin; and CTLA-4/Ig.   
     
     
         17 . The method of  claim 16 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         18 . The method of  claim 7 , further comprising the step of:
 co-administering to the human patient at least one enhancer selected from the group consisting of: high molecular weight hyaluronic acid; IL-2; IL-15; TGF-β; all-trans retinoic acid; rapamycin; anti-CD3; anti-CD28; vitamin D3; dexamethasone; IL-10; idolamine-2,3-dioxygenase; FTY720; a sphingosine kinase 1 inhibitor; cholera toxin B subunit; ovalbumin; Flt2L; sirolimus; anti-thymocyte globulin; and CTLA-4/Ig.   
     
     
         19 . The method of  claim 18 , wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         20 . The method of  claim 9 , further comprising the step of:
 co-administering to the human patient at least one enhancer selected from the group consisting of: high molecular weight hyaluronic acid; IL-2; IL-15; TGF-β; all-trans retinoic acid; rapamycin; anti-CD3; anti-CD28; vitamin D3; dexamethasone; IL-10; idolamine-2,3-dioxygenase; FTY720; a sphingosine kinase 1 inhibitor; cholera toxin B subunit; ovalbumin; Flt2L; sirolimus; anti-thymocyte globulin; and CTLA-4/Ig.   
     
     
         21 . The method of  claim 21 , Wherein an increase in the number of regulatory T-cells responsive to the synthetic peptide results in the human patient. 
     
     
         22 . The method of  claim 1 , wherein the human patient has early AMD. 
     
     
         23 . The method of  claim 1 , wherein the patient has intermediate AMD. 
     
     
         24 . The method of  claim 1 , wherein the patient has late AMD. 
     
     
         25 - 81 . (canceled) 
     
     
         82 . A pharmaceutical composition, comprising
 a synthetic peptide having the sequence VTVDVTNNTEKTVKK (SEQ ID NO: 3) or a variant thereof in which a single amino acid is substituted with a different amino acid.