Inhibitor of IGFBP3/TMEM219 Axis and Diabetes

Abstract

The present invention relates to the role of the IGFBP3/TMEM219 axis in the onset of diabetes and the related use of IGFBP3/TMEM219 axis inhibitors for the treatment and/or prevention of diabetes. The invention also relates to a method to identify a subject at risk of developing Type 1 and/or Type 2 diabetes and relative kit.

1 .- 19 . (canceled) 
     
     
         20 . A method of treating and/or preventing diabetes in a subject, comprising:
 administering an effective amount of an inhibitor of the IGFBP3/TMEM219 axis to a subject, wherein said inhibitor comprises a fragment of the receptor TMEM219, said fragment comprising an extracellular domain of TMEM219.   
     
     
         21 . The method of  claim 20 , wherein said inhibitor is a fragment of the receptor TMEM219. 
     
     
         22 . The method of  claim 20 , wherein said inhibitor is ecto-TMEM219. 
     
     
         23 . The method of  claim 20 , wherein said inhibitor is soluble. 
     
     
         24 . The method of  claim 20 , wherein said inhibitor is pegylated. 
     
     
         25 . The method of  claim 20 , wherein said inhibitor is a host cell genetically engineered to express said fragment of the receptor TMEM219. 
     
     
         26 . The method of  claim 20 , wherein the diabetes is Type-1 or Type-2 diabetes. 
     
     
         27 . The method of  claim 20 , wherein the subject is selected from the group consisting of: a subject at risk of developing Type-1 and/or Type-2 diabetes, and a subject with early stage Type-1 and/or Type-2 diabetes. 
     
     
         28 . The method of  claim 20 , wherein said inhibitor of the IGFBP3/TMEM219 axis is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier. 
     
     
         29 . The method of  claim 28 , wherein said pharmaceutical composition comprises a second therapeutic agent. 
     
     
         30 . The method of  claim 29 , wherein the second therapeutic agent is selected from the group consisting of: insulin in any form, Pramlintide (Symlin), angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), Aspirin, Cholesterol-lowering drugs. Metformin (Glucophage, Glumetza, others), Sulfonylureas (glyburide (DiaBeta, Glynase), glipizide (Glucotrol) and glimepiride (Amaryl), Meglitinides (for instance repaglinide (Prandin) and nateglinide (Starlix)), Thiazolidinediones (Rosiglitazone (Avandia) and pioglitazone (Actos) for examples), DPP-4 inhibitors (sitagliptin (Januvia), saxagliptin (Onglyza) and linagliptin (Tradjenta)), GLP-1 receptor agonists (Exenatide (Byetta) and liraglutide (Victoza)), SGLT2 inhibitors, examples include canagliflozin (Invokana) and dapagliflozin (Farxiga). 
     
     
         31 . A method of treating and/or preventing diabetes in a subject, comprising:
 administering an effective amount of an inhibitor of the IGFBP3/TMEM219 axis to a subject, wherein said inhibitor comprises a polynucleotide coding for a fragment of the receptor TMEM219, said fragment comprising an extracellular domain of TMEM219.   
     
     
         32 . The method of  claim 31 , wherein said polynucleotide codes for ecto-TMEM219. 
     
     
         33 . The method of  claim 31 , wherein said inhibitor is soluble. 
     
     
         34 . The method of  claim 31 , wherein said inhibitor is a vector comprising or expressing said polynucleotide. 
     
     
         35 . The method of  claim 31 , wherein said inhibitor is a host cell comprising said polynucleotide. 
     
     
         36 . The method of  claim 31 , wherein the diabetes is Type-1 or Type-2 diabetes. 
     
     
         37 . The method of  claim 31 , wherein the subject is selected from the group consisting of: a subject at risk of developing Type-1 and/or Type-2 diabetes, and a subject with early stage Type-1 and/or Type-2 diabetes. 
     
     
         38 . The method of  claim 31 , wherein said inhibitor of the IGFBP3/TMEM219 axis is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier. 
     
     
         39 . The method of  claim 38 , wherein said pharmaceutical composition comprises a second therapeutic agent. 
     
     
         40 . The method of  claim 39 , wherein the therapeutic agent is selected from the group consisting of: insulin in any form, Pramlintide (Symlin), angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), Aspirin, Cholesterol-lowering drugs. Metformin (Glucophage, Glumetza, others), Sulfonylureas (glyburide (DiaBeta, Glynase), glipizide (Glucotrol) and glimepiride (Amaryl), Meglitinides (for instance repaglinide (Prandin) and nateglinide (Starlix)), Thiazolidi nediones (Rosiglitazone (Avandia) and pioglitazone (Actos) for examples), DPP-4 inhibitors (sitagliptin (Januvia), saxagliptin (Onglyza) and linagliptin (Tradjenta)), GLP-1 receptor agonists (Exenatide (Byetta) and liraglutide (Victoza)), SGLT2 inhibitors, examples include canagliflozin (Invokana) and dapagliflozin (Farxiga). 
     
     
         41 . A composition comprising an inhibitor of the IGFBP3/TMEM219 axis, wherein said inhibitor comprises a fragment of the receptor TMEM219 or a polynucleotide coding for said fragment, wherein said fragment comprises an extracellular domain of TMEM219. 
     
     
         42 . The composition of  claim 41 , wherein said inhibitor is a fragment of the receptor TMEM219. 
     
     
         43 . The composition of  claim 41 , wherein said inhibitor is ecto-TMEM219. 
     
     
         44 . The composition of  claim 41 , wherein said polynucleotide codes for ecto-TMEM219. 
     
     
         45 . The composition of  claim 41 , wherein said inhibitor is a vector comprising or expressing said polynucleotide. 
     
     
         46 . The composition of  claim 41 , wherein said inhibitor is a host cell genetically engineered to express said fragment of the receptor TMEM219. 
     
     
         47 . The composition of  claim 41 , wherein said inhibitor is a host cell comprising said polynucleotide 
     
     
         48 . The composition of  claim 41 , wherein said composition comprises a pharmaceutical composition comprising said inhibitor and a pharmaceutically acceptable carrier. 
     
     
         49 . The composition of  claim 48 , wherein said pharmaceutical composition comprises a second therapeutic agent.