Methods of treating diabetes and/or promoting survival of pancreatic islets after transplantation
Disclosed herein are methods for treating/and or preventing diabetes using a specific inhibitor of SMAD7 expression or function. Also disclosed are methods of promoting organ and/or cell, e.g., pancreatic islet cell, survival after transplantation using a specific inhibitor of SMAD7 expression or function.
1. A method of treating diabetes by preventing pancreatic islet β cell destruction, the method comprising administering to a patient in need thereof an effective amount of a SMAD7 antisense oligonucleotide comprising a sequence selected from the group consisting of the nucleotide sequences of SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, and SEQ ID NO: 12, wherein the diabetes is selected from the group consisting of Type 1 diabetes, Type 2 diabetes, and gestational diabetes.
2. The method of claim 1 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 6 or SEQ ID NO: 10.
3. The method of claim 1 , wherein the SMAD7 antisense oligonucleotide is administered parenterally.
4. The method of claim 3 , wherein the SMAD7 antisense oligonucleotide is administered subcutaneously.
5. The method of claim 1 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 10.
6. The method of claim 5 , wherein all internucleoside bonds of the SMAD7 antisense oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 10 are phosphorothioate bonds.
7. The method of claim 1 , wherein two or more of the internucleoside bonds of the SMAD7 antisense oligonucleotide comprising SEQ ID NO: 10 are phosphorothioate bonds.
8. A method of treating diabetes by preventing pancreatic islet β cell destruction, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising:
an effective amount of a SMAD7 antisense oligonucleotide comprising a sequence selected from the group consisting of the nucleotide sequences of SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, and SEQ ID NO: 12; and
a pharmaceutically acceptable carrier, wherein the diabetes is selected from the group consisting of Type 1 diabetes, Type 2 diabetes, and gestational diabetes.
9. The method of claim 8 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 6 or SEQ ID NO: 10.
10. The method of claim 8 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 10.
11. The method of claim 10 , wherein all internucleoside bonds of the SMAD7 antisense oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 10 are phosphorothioate bonds.
12. The method of claim 8 , wherein the pharmaceutical composition is administered parenterally.
13. The method of claim 12 , wherein the pharmaceutical composition is administered subcutaneously.
14. The method of claim 8 , wherein two or more of the internucleoside bonds of the SMAD7 antisense oligonucleotide comprising SEQ ID NO: 10 are phosphorothioate bonds.
15. A method of treating hyperglycemia by preventing pancreatic islet β cell destruction, the method comprising administering to a patient in need thereof an effective amount of a SMAD7 antisense oligonucleotide comprising a sequence selected from the group consisting of the nucleotide sequences of SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, and SEQ ID NO: 12.
16. The method of claim 15 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 10.
17. The method of claim 16 , wherein all internucleoside bonds of the SMAD7 antisense oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 10 are phosphorothioate bonds.
18. The method of claim 15 , wherein the SMAD7 antisense oligonucleotide is administered parenterally.
19. The method of claim 18 , wherein the SMAD7 antisense oligonucleotide is administered subcutaneously.
20. The method of claim 15 , wherein two or more of the internucleoside bonds of the SMAD7 antisense oligonucleotide comprising SEQ ID NO: 10 are phosphorothioate bonds.
21. A method of treating hyperglycemia by preventing pancreatic islet β cell destruction, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising:
an effective amount of a SMAD7 antisense oligonucleotide comprising a sequence selected from the group consisting of the nucleotide sequences of SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, and SEQ ID NO: 12; and
a pharmaceutically acceptable carrier.
22. The method of claim 21 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 10.
23. The method of claim 22 , wherein all internucleoside bonds of the SMAD7 antisense oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 10 are phosphorothioate bonds.
24. The method of claim 21 , wherein the pharmaceutical composition is administered parenterally.
25. The method of claim 24 , wherein the pharmaceutical composition is administered subcutaneously.
26. The method of claims 21 , wherein two or more of the internucleoside bonds of the SMAD7 antisense oligonucleotide comprising SEQ ID NO: 10 are phosphorothioate bonds.