Methods of treating diabetes and/or promoting survival of pancreatic islets after transplantation

Abstract

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 and/or preventing a condition of insulin deficiency, comprising administering to a patient in need thereof an effective amount of a SMAD7 antisense oligonucleotide comprising the nucleotide 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 condition is selected from the group consisting of: latent autoimmune diabetes, a metabolic imbalance, a pre-diabetic state, metabolic syndrome, and a lipid or glucose related disorder. 
     
     
         2 - 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 6 or SEQ ID NO: 10. 
     
     
         8 . The method of  claim 1 , wherein the SMAD7 antisense oligonucleotide is administered parenterally. 
     
     
         9 . The method of  claim 8 , wherein the SMAD7 antisense oligonucleotide is administered subcutaneously. 
     
     
         10 - 15 . (canceled) 
     
     
         16 . The method of  claim 1 , 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 16 , wherein two or more of the internucleoside bonds of the SMAD7 antisense oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 10 are phosphorothioate bonds. 
     
     
         19 . The method of  claim 1 , wherein the lipid or glucose related disorder is selected from the group consisting of hyperlipidemia and hypercholesterolemia. 
     
     
         20 . The method of  claim 1 , wherein the metabolic imbalance is selected from the group consisting of diabetes mellitus, gestational diabetes, a genetic defect of β-cell function, a genetic defect in insulin action, a disease of the exocrine pancreas, an endocrinopathy, a drug or chemical-induced infection, and a genetic syndrome associated with diabetes. 
     
     
         21 . The method of  claim 1 , wherein the method is effective to prevent pancreatic islet β cell destruction. 
     
     
         22 . A method of treating and/or preventing a condition of insulin deficiency, comprising administering to a patient in need thereof a pharmaceutical composition comprising:
 an effective amount of a SMAD7 antisense oligonucleotide comprising the nucleotide 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 condition is selected from the group consisting of: latent autoimmune diabetes, a metabolic imbalance, a pre-diabetic state, metabolic syndrome, and a lipid or glucose related disorder.   
     
     
         23 . The method of  claim 22 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 6 or SEQ ID NO: 10. 
     
     
         24 . The method of  claim 22 , wherein the SMAD7 antisense oligonucleotide comprises the nucleotide sequence of SEQ ID NO: 10. 
     
     
         25 . The method of  claim 24 , wherein all internucleoside bonds of the SMAD7 antisense oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 10 are phosphorothioate bonds. 
     
     
         26 . The method of  claim 24 , wherein two or more of the internucleoside bonds of the SMAD7 antisense oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 10 are phosphorothioate bonds. 
     
     
         27 . The method of  claim 22 , wherein the pharmaceutical composition is administered parenterally. 
     
     
         28 . The method of  claim 22 , wherein the pharmaceutical composition is administered subcutaneously. 
     
     
         29 . The method of  claim 22 , wherein the lipid or glucose related disorder is selected from the group consisting of hyperlipidemia and hypercholesterolemia. 
     
     
         30 . The method of  claim 22 , wherein the metabolic imbalance is selected from the group consisting of diabetes mellitus, gestational diabetes, a genetic defect of β-cell function, a genetic defect in insulin action, a disease of the exocrine pancreas, an endocrinopathy, a drug or chemical-induced infection, and a genetic syndrome associated with diabetes. 
     
     
         31 . The method of  claim 22 , wherein the method is effective to prevent pancreatic islet β cell destruction.