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 type 1 diabetes mellitus autoimmunity in a subject comprising administering an effective amount of a fusion protein composition which comprises a fusion protein and an oil-based carrier, wherein the fusion protein comprises the extracellular domain of CTLA4 and a portion of an immunoglobulin molecule and said oil-based carrier is an oil-in-water emulsion comprising Incomplete Freund's Adjuvant (IFA) or Montanide Incomplete Seppic Adjuvant (ISA).
2. The method of claim 1 , wherein the oil-in-water emulsion comprises IFA.
3. The method of claim 1 , wherein the oil-in-water emulsion comprises Montanide ISA.
4. A method of treating type 1 diabetes mellitus autoimmunity in a subject in need thereof, the method comprising administering a therapeutically effective regimen of a composition comprising a fusion protein to the subject,
wherein the fusion protein comprises the extracellular domain of CTLA4 and a portion of an immunoglobulin molecule to the subject, and
wherein the therapeutically effective regimen comprises administering an effective amount of the composition over a period of at least 6 months at a frequency between about once a day and about once every two months.
5. The method of claim 4 , wherein the therapeutically effective regimen comprises administering the effective amount of the composition at a frequency of about once a week.
6. The method of claim 4 , wherein the therapeutically effective regimen comprises administering the effective amount of the composition at a frequency of about once every two weeks.
7. The method of claim 4 , wherein the therapeutically effective regimen comprises administering the effective amount of the composition at a frequency of about once a month.
8. The method of claim 4 , wherein the therapeutically effective regimen comprises administering the effective amount of the composition at a frequency of about once every 2 months.
9. The method of claim 4 , wherein the subject is human.
10. The method of claim 9 , wherein at the time of beginning the administration of the therapeutically effective regimen the subject had been diagnosed with type 1 diabetes mellitus within the last 200 days.
11. The method of claim 10 , wherein at the time of beginning the administration of the therapeutically effective regimen the subject had been diagnosed with type 1 diabetes mellitus within the last 100 days.
12. The method of claim 10 , wherein at least once between the time of diagnosis and the time of beginning the administration of the therapeutically effective regimen, the subject had a stimulated C-peptide concentration of at least about 0.2 nmol/L as measured by a mixed-meal tolerance test (MMTT).
13. The method of claim 4 , wherein at the time of beginning the administration of the therapeutically effective regimen the expression of at least one diabetes-related autoantibody had been detected in the subject.
14. The method of claim 4 , wherein the subject receives daily insulin during the administration of the therapeutically effective regimen.
15. The method of claim 4 , wherein the therapeutically effective regimen comprises administering the effective amount of the composition over a period of at least one year.
16. The method of claim 15 , wherein the therapeutically effective regimen comprises administering the effective amount of the composition over a period of at least two years.
17. The method of claim 4 , wherein the effective amount is between about 5 mg/kg and 50 mg/kg.
18. The method of claim 4 , wherein the composition comprises an oil-based carrier which is an oil-in-water emulsion comprising Incomplete Freund's Adjuvant (IFA) or Montanide Incomplete Seppic Adjuvant (ISA).
19. The method of claim 4 , further comprising measuring levels of C-peptide in the subject at least about once every six months during the administration of the therapeutically effective regimen.
20. A method of treating type 1 diabetes mellitus in a human subject diagnosed with type 1 diabetes mellitus within the last 100 days, the method comprising administering a therapeutically effective regimen of a composition comprising a fusion protein to the subject,
wherein the fusion protein comprises the extracellular domain of CTLA 4 and a portion of an immunoglobulin molecule to the subject, and
wherein the therapeutically effective regimen comprises administering an effective amount of the composition over a period of at least 6 months at a frequency between about once a week and about once every two months.