Combination therapies for treating type 1 diabetes

Abstract

In accordance with the subject invention, combination therapies can be used to modulate a patient's immune response in order to prevent, delay and/or reverse type 1 diabetes.

We claim: 
     
         1 . A method for enhancing the ability of CD4+ CD25+ T cells to defend against a pathological autoimmune process, wherein said method comprises administering, to a patient in need of an enhanced defense against a pathological autoimmune process, a combination therapy, wherein the combination therapy consists of administering anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF); and optionally,
 one or more additional agents selected from stem cells, agents that reduce a pathological autoimmune response, exenatide, DPPIV inhibitors, EGF, INGAP, a local cytokine, alpha-1 antitrypsin (AAT), vitamin D, anti-oxidants, anti-inflammatory agents, glulisine, glucagons, modulators of cytokines, anti-apoptotic molecules, exendin-4, carriers, adjuvants, binders, diluents, excipients, lubricants, glidants, flavoring agents, preservatives, coloring agents, chelating agents, buffers, and agents for the adjustment of tonicity.   
     
     
         2 . The method, according to  claim 1 , which is used to treat a condition selected from the group consisting of type 1 diabetes, rheumatoid arthritis, multiple sclerosis, thyroiditis, inflammatory bowel disease, Addison's disease, pancreas transplantation, kidney transplantation, islet transplantation, heart transplantation, lung transplantation, and liver transplantation. 
     
     
         3 . The method, according to  claim 1 , wherein the combination therapy consists of administering anti-thymocyte globulin (ATG), granulocyte colony-stimulating factor (G-CSF), and one or more agents selected from alpha-1 antitrypsin (AAT), vitamin D, anti-oxidants, anti-inflammatory agents and modulators of cytokines; and optionally,
 one or more additional agents selected from stem cells, agents that reduce a pathological autoimmune response, exenatide, DPPIV inhibitors, EGF, INGAP, a local cytokine, glulisine, glucagons, anti-apoptotic molecules, exendin-4, carriers, adjuvants, binders, diluents, excipients, lubricants, glidants, flavoring agents, preservatives, coloring agents, chelating agents, buffers, and agents for the adjustment of tonicity.   
     
     
         4 . The method, according to  claim 1 , wherein the combination therapy consists of administering anti-thymocyte globulin (ATG), granulocyte colony-stimulating factor (G-CSF), and one or more agents selected from glulisine, glucagons, DPP4 inhibitors, anti-apoptotic molecules and exendin-4; and optionally,
 one or more additional agents selected from stem cells, agents that reduce a pathological autoimmune response, exenatide, DPPIV inhibitors, EGF, INGAP, a local cytokine, alpha-1 antitrypsin (AAT), vitamin D, anti-oxidants, anti-inflammatory agents, modulators of cytokines, carriers, adjuvants, binders, diluents, excipients, lubricants, glidants, flavoring agents, preservatives, coloring agents, chelating agents, buffers, and agents for the adjustment of tonicity.   
     
     
         5 . The method, according to  claim 4 , wherein the glucagon is glucagon-like peptide-1 (GLP-1). 
     
     
         6 . The method according to  claim 1 , wherein the therapy is administered prior to a clinical manifestation of type 1 diabetes. 
     
     
         7 . The method, according to  claim 1 , wherein the combination therapy is administered to a patient who has been determined to have at least one of the following: islet cell antibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADA), and insulinoma-associated-2-autoantibodies (IA-2A). 
     
     
         8 . The method, according to  claim 7 , wherein the patient has at least two of the listed antibodies. 
     
     
         9 . The method, according to  claim 1 , wherein beta cell mass of the patient has declined to less than 50% but more than 10% of normal. 
     
     
         10 . The method, according to  claim 1 , wherein the patient has been determined to be genetically pre-disposed to type 1 diabetes. 
     
     
         11 . The method, according to  claim 1 , wherein the therapy is done in conjunction with islet transplantation.