Type i diabetes therapy

Abstract

The present invention relates to novel methods and therapies for treating, preventing or delaying the onset of type 1 diabetes. In one aspect, the invention provides a method of preventing, delaying the onset of, or delaying the progression of, type 1 diabetes (T1D) in an individual, the method comprising providing in the individual an anti-inflammatory compound; and a pancreatic autoantigen or a derivative or variant thereof; thereby preventing, delaying the onset of, or delaying the progression of, T1D in the individual.

1 - 53 . (canceled) 
     
     
         54 . A method of delaying the progression of type 1 diabetes (T1D) in an individual having T1D, the method comprising providing in the individual:
 an anti-inflammatory compound, wherein the anti-inflammatory compound is a JAK inhibitor; and   a pancreatic autoantigen or a derivative or variant thereof;   thereby delaying the progression of T1D in the individual.   
     
     
         55 . The method of  claim 54 , wherein the pancreatic autoantigen or a derivative or variant thereof is selected from the group consisting of proinsulin, insulin, islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP), glutamate decarboxylase (GAD), islet-antigen 2 (IA-2) and zinc transporter 8 (ZnT8); optionally wherein the pancreatic autoantigen or a derivative or variant thereof is proinsulin. 
     
     
         56 . The method of  claim 54 , wherein the individual having T1D displays at least one symptom of T1D selected from the group consisting of: the individual has 2 or more autoantibodies against β-cell specific antigens, polyuria, polydipsia, weight loss, fatigue, and diabetic ketoacidosis (DKA), optionally wherein the pancreatic autoantigen or a derivative or variant thereof is selected from the group consisting of proinsulin, insulin, islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP), glutamate decarboxylase (GAD), islet-antigen 2 (IA-2) and zinc transporter 8 (ZnT8). 
     
     
         57 . The method of  claim 54 , wherein the T1D is early stage pre-symptomatic T1D or is newly diagnosed symptomatic T1D. 
     
     
         58 . The method of  claim 54 , wherein the T1D is early stage pre-symptomatic T1D, and wherein the individual having T1D has one or more of the following indicators of early stage type 1 diabetes: autoimmunity to at least two β-cell specific antigens, dysglycaemia, evidence of β-islet cell loss, reduced endogenous insulin production. 
     
     
         59 . The method of  claim 54 , wherein:
 (i) the JAK inhibitor and pancreatic autoantigen or a derivative or variant thereof are provided simultaneously; or   (ii) wherein the JAK inhibitor is provided prior to the pancreatic autoantigen or a derivative or variant thereof, optionally is continued to be provided during the time the pancreatic autoantigen or a derivative or variant thereof is provided; or   (iii) wherein the pancreatic autoantigen or a derivative or variant thereof is provided prior to the JAK inhibitor, optionally is continued to be provided during the time the JAK inhibitor is provided.   
     
     
         60 . The method of  claim 54 , wherein the JAK inhibitor binds to the active site of a JAK. 
     
     
         61 . The method of  claim 54 , wherein the JAK inhibitor competes with or prevents a substrate of JAK from binding to a JAK. 
     
     
         62 . The method of  claim 54 , wherein the JAK inhibitor directly inhibits the enzymatic activity of a JAK. 
     
     
         63 . The method of  claim 54 , wherein the JAK inhibitor inhibits the expression of a JAK. 
     
     
         64 . The method of  claim 54 , wherein the JAK inhibitor is selective for JAK1, JAK2, JAK3, TYK2 or a combination thereof. 
     
     
         65 . The method of  claim 54 , wherein the JAK inhibitor is selective for JAK1. 
     
     
         66 . The method of  claim 54 , wherein the JAK inhibitor is selective for JAK3. 
     
     
         67 . The method of  claim 54 , wherein the JAK inhibitor is selective for JAK1 and JAK2. 
     
     
         68 . The method of  claim 54 , wherein the JAK inhibitor is selective for JAK1 and TYK2. 
     
     
         69 . The method of  claim 54 , wherein the JAK inhibitor is selected from the group consisting of: Ruxolitinib, Tofacitinib, Oclacitinib, Baricitinib, Filgotinib, Gandotinib, Lestaurtinib, Momelotinib, Pacritinib, Upadacitinib, Peficitinib, TG1011348, AZD1480, BMS-911543, XL019, and NS018. 
     
     
         70 . The method of  claim 54 , wherein the JAK inhibitor is Baricitinib or Ruxolitinib. 
     
     
         71 . The method of  claim 54 , wherein the JAK inhibitor is provided to the individual by administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of the JAK inhibitor; and/or
 wherein the pancreatic autoantigen or a derivative or variant thereof is provided in the individual by administering to the individual a pharmaceutical composition comprising a pancreatic autoantigen or a derivative or variant thereof to the individual.   
     
     
         72 . The method of  claim 54 , wherein the JAK inhibitor is administered orally, by inhalation, subcutaneously, intravenously, intranasally, intramuscularly or intradermally; and/or
 wherein the pancreatic autoantigen or derivative or variant thereof is administered orally, by inhalation, subcutaneously, intravenously, intranasally, intramuscularly or intradermally.   
     
     
         73 . The method of  claim 54 , wherein the pancreatic autoantigen or a derivative or variant thereof is provided in the individual by administering to the individual, a composition comprising a nucleic acid construct for expressing the pancreatic autoantigen or derivative or variant thereof in the individual; and/or
 wherein the JAK inhibitor is provided in the individual by administering to the individual, a composition comprising a nucleic acid construct for expressing the JAK inhibitor in the individual.   
     
     
         74 . A composition comprising a JAK inhibitor and a pancreatic autoantigen or a derivative or variant thereof. 
     
     
         75 . The composition of  claim 74 , wherein the pancreatic autoantigen or a derivative or variant thereof is selected from the group consisting of proinsulin, insulin, islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP), glutamate decarboxylase (GAD), islet-antigen 2 (IA-2) and zinc transporter 8 (ZnT8); and/or
 wherein the JAK inhibitor is selective for JAK1, JAK2, JAK3, TYK2, or a combination thereof.