CTLA4 FUSION PROTEINS FOR THE TREATMENT OF DIABETES
A method of treating, preventing, or delaying the progression of Type 1 diabetes mellitus autoimmunity by administering an effective amount of a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) molecule is provided herewith. The CTLA4 molecule may be a fusion protein of a CTLA4 extracellular region and an immunoglobulin, such as abatacept.
1 . A method of treating diabetes mellitus in a subject comprising administering an effective amount of a fusion protein composition comprising a T-cell co-stimulation antagonist and a portion of an immunoglobulin molecule.
2 . The method of claim 1 wherein the T-cell co-stimulation antagonist comprises the extracellular domain of CTLA4, an effective fragment of the extracellular domain or immunologically active variant of the extracellular domain.
3 . The method of claim 1 wherein the T-cell co-stimulation antagonist binds a B7 antigen expressed on B cells and/or on antigen presenting cells (APCs).
4 . The method of claim 1 wherein the composition comprises Abatacept.
5 . The method of claim 1 wherein the composition is administered as a pharmaceutically acceptable salt.
6 . The method of claim 1 wherein the composition further comprises an oil-based carrier.
7 . The method of claim 6 , wherein said oil-based carrier is a water-in-oil emulsion.
8 . The method of claim 6 , wherein said oil-based carrier is an oil-in-water emulsion.
9 . The method of claim 6 , wherein said oil-based carrier is IFA.
10 . The method of claim 6 , wherein said oil-based carrier is Montanide ISA.
11 . The method of claim 1 , wherein the composition is administered by intravenous infusion.
12 . The method of claim 11 , wherein the composition is administered by intravenous infusion in about 50 to 200 ml of physiological saline.
13 . The method of claim 11 , wherein the composition is administered at a dose ranging from about 5 mg/kg to about 50 mg/kg
14 . The method of claim 11 , wherein the intravenous infusion of the composition is repeated over time.
15 . The method of claim 11 , wherein the intravenous infusion of the composition is repeated at least once following a time interval ranging from about one week to about two months.
16 . The method of claim 11 , wherein the composition is administered at a dose ranging from about 250 to 2000 mg.
17 . The method of claim 16 , wherein the composition is administered at a dose of 500 mg.
18 . The method of claim 16 , wherein the composition is administered at a dose of 750 mg.
19 . The method of claim 16 , wherein the composition is administered at a dose of 1000 mg.
20 . The method of claim 1 , wherein the method further comprises determining levels of C-peptide in blood samples taken from the subject over time as an indicator of effectiveness of the treatment in inhibiting activation of auto-aggressive T-cells.
21 . The method of claim 20 , wherein the effectiveness of the composition in inhibiting activation of auto-aggressive T-cells is indicated by maintenance of C-peptide production or a delay in reduction of C-peptide production as compared to a standard.
22 . The method of claim 20 , wherein the effectiveness of the composition in inhibiting activation of auto-aggressive T-cells is indicated by improved HbA1c or reduction in the use of insulin by said subject as compared to a standard.
23 . The method of claim 20 , wherein the reduction of C-peptide production in said subject is delayed for at least six months.
24 . The method of claim 20 , wherein the reduction of C-peptide production in said subject is delayed for at least nine months.
25 . The method of claim 1 , wherein the subject is white.
26 . The method of claim 1 , wherein said treating diabetes mellitus in a subject comprising preventing the onset of diabetes in a subject at risk for diabetes mellitus.
27 . The method of claim 1 , wherein said treating diabetes mellitus in a subject comprising delaying the onset of diabetes by at least six months in a subject at risk for diabetes mellitus.