IMMUNE MODULATION FOR THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION
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.