Compositions, methods and uses for the treatment of diabetic neuropathies

Abstract

The present invention relates to compositions and methods for the treatment of diabetic neuropathies. More particularly, this invention relates to compositions and methods for promoting nerve regeneration in a subject suffering from, or at risk of suffering from a diabetic neuropathy, and for protecting nervous system cells against the stresses resulting from the perturbation of glucose homeostasis. More specifically, the present invention relates to novel single or combination therapies for diabetic neuropathies, comprising diabetic peripheral neuropathy, diabetic proximal neuropathy, diabetic autonomic neuropathy and diabetic focal neuropathy, based on restoring dorsal root ganglion neurons and other nerves integrity.

1 . A method for the treatment of a diabetic neuropathy in a subject in need thereof comprising administering to the subject a composition comprising at least two drugs selected from acamprosate, almitrine, amlexanox, azelastine, baclofen, carbetapentane, cimetidine, cinacalcet, dexbrompheniramine, diethylcarbamazine, diprophylline, D-mannose, fenspiride, fexofenadine, idebenone, ifenprodil, levosimendan, mexiletine, nicergoline, piribedil, rilmenidine, tolfenamic acid, tolperisone, torasemide and triamterene, or salts, prodrugs, derivatives, or sustained release formulations thereof. 
     
     
         2 . The method of  claim 1 , comprising administering to the subject:
 at least one drug selected from acamprosate, baclofen, carbetapentane, cimetidine, cinacalcet, dexbrompheniramine, diethylcarbamazine, ifenprodil, levosimendan, mexiletine, nicergoline, rilmenidine, tolperisone, torasemide and triamterene, or a salt, prodrug, derivative, or sustained release formulation thereof, and   at least one distinct drug selected form acamprosate, almitrine, amlexanox, azelastine, baclofen, carbetapentane, cimetidine, cinacalcet, dexbrompheniramine, diethylcarbamazine, diprophylline, D-mannose, fenspiride, fexofenadine, idebenone, ifenprodil, levosimendan, mexiletine, nicergoline, piribedil, rilmenidine, tolfenamic acid, tolperisone, torasemide and triamterene, or a salt, prodrug, derivative, or sustained release formulation thereof.   
     
     
         3 . The method of  claim 1 , comprising administering to the subject:
 at least one drug selected from acamprosate, cinacalcet, levosimendan, torasemide and triamterene, or a salt, prodrug, derivative, or sustained release formulation thereof, and   at least one distinct drug selected form acamprosate, almitrine, amlexanox, azelastine, baclofen, carbetapentane, cimetidine, cinacalcet, dexbrompheniramine, diethylcarbamazine, diprophylline, D-mannose, fenspiride, fexofenadine, idebenone, ifenprodil, levosimendan, mexiletine, nicergoline, piribedil, rilmenidine, tolfenamic acid, tolperisone, torasemide and triamterene, or a salt, prodrug, derivative, or sustained release formulation thereof.   
     
     
         4 . The method of  claim 1 , comprising administering to the subject:
 at least one drug selected from acamprosate, cinacalcet, levosimendan, torasemide and triamterene, or a salt, prodrug, derivative, or sustained release formulation thereof, and   at least one distinct drug selected form acamprosate, baclofen, carbetapentane, cimetidine, cinacalcet, dexbrompheniramine, diethylcarbamazine, ifenprodil, levosimendan, mexiletine, nicergoline, rilmenidine, tolperisone, torasemide and triamterene, or a salt, prodrug, derivative, or sustained release formulation thereof.   
     
     
         5 . The method of  claim 1 , comprising administering to the subject at least two drugs selected from acamprosate, baclofen, carbetapentane, cimetidine, cinacalcet, dexbrompheniramine, diethylcarbamazine, ifenprodil, levosimendan, mexiletine, nicergoline, rilmenidine, tolperisone, torasemide and triamterene, or salts, prodrugs, derivatives, or sustained release formulations thereof. 
     
     
         6 . The method of  claim 1 , comprising administering to the subject at least one of the following drug combinations:
 acamprosate and cinacalcet,   acamprosate and levosimendan,   acamprosate and torasemide,   acamprosate and triamterene,   acamprosate and baclofen,   cinacalcet and levosimendan,   cinacalcet and torasemide,   cinacalcet and triamterene,   torasemide and triamterene,   levosimendan and torasemide, or   levosimendan and triamterene, or   
       salts, prodrugs, derivatives, or sustained release formulations thereof. 
     
     
         7 . The method of  claim 1 , further comprising administering to the subject at least one drug selected from duloxetine and pregabalin, or a salt, prodrug, derivative, or sustained release formulation thereof. 
     
     
         8 . The method of  claim 1 , further comprising administering to the subject at least one antidiabetic agent selected from acarbose, acetohexamide, alogliptin, berberine, bezafibrate, bromocriptine, buformin, carbutamide, chlorpropamide, chromium picolinate, ciprofibrate, clofibrate, colesevelam, dexfenfluramine, dutogliptin, exenatide, fenofibrate, gemfibrozil, gemigliptin, glibenclamide, glibornuride, glicetanile, gliclazide, glimepiride, glipizide, gliquidone, glisentide, glyclopyramide, imidapril, insulin, inulin, lipoic acid, linagliptin, liraglutide, mecobalamin, metformin, miglitol, mitiglinide, nateglinide, orlistat, phenformin, pioglitazone, pramlintide, repaglinide, rosiglitazone, saxagliptin, sitagliptin, tolazamide, tolbutamide, vildagliptin or voglibose, or a salt, prodrug, derivative, or sustained release formulation thereof. 
     
     
         9 . The method of  claim 8 , wherein the at least one further antidiabetic agent is metformin, or a salt, prodrug, derivative, or sustained release formulation thereof. 
     
     
         10 . The method of  claim 1 , wherein the subject is suffering from or at risk of suffering from a diabetic neuropathy. 
     
     
         11 . The method of  claim 10 , wherein the diabetic neuropathy is selected from a diabetic peripheral neuropathy, a diabetic proximal neuropathy, a diabetic autonomic neuropathy and a diabetic focal neuropathy. 
     
     
         12 . The method of  claim 1 , wherein the subject is suffering from diabetes type I or II, chronic hyperglycaemia, impaired fasting glycaemia, impaired glucose tolerance or obesity. 
     
     
         13 . A method of  claim 1 , for use in promoting nerve regeneration in a subject suffering from or at risk of suffering from a diabetic neuropathy. 
     
     
         14 . A method of  claim 1 , for use in protecting nervous system cells against the stresses resulting from the perturbation of glucose homeostasis. 
     
     
         15 . The method of  claim 1 , which wherein the composition further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         16 . The method of  claim 1 , wherein the drugs in said composition are formulated or administered simultaneously, separately or sequentially. 
     
     
         17 . The method of  claim 1 , wherein said composition is administered repeatedly to the subject.