Methods of treating diabetes and compositions capable of same

Abstract

A composition of matter is disclosed which comprises isolated oligomers of human islet amyloid polypeptide (IAPP). Antibodies recognizing same are also disclosed. Use of the composition of matter and the antibodies are also disclosed.

What is claimed is: 
     
         1 . A composition of matter comprising isolated non-crosslinked oligomers of human islet amyloid polypeptide (IAPP), wherein the majority of said oligomers are dimers and/or trimers and wherein said oligomers are stable for up to 7 days. 
     
     
         2 . The composition of matter of  claim 1 , wherein said oligomers are stable for up to 7 days. 
     
     
         3 . The composition of matter of  claim 1 , wherein said composition comprises an anionic surfactant. 
     
     
         4 . The composition of matter of  claim 3 , wherein said anionic surfactant comprises sodium dodecyl sulfate (SDS). 
     
     
         5 . A method of generating a composition of matter comprising isolated oligomers of human islet amyloid polypeptide (IAPP), the method comprising:
 (a) dissolving human IAPP in an agent that eliminates structured forms of IAPP;   (b) removing said agent; and   (c) redissolving said non-structured form of IAPP in a solvent and an anionic surfactant, thereby generating the composition of matter.   
     
     
         6 . The method of  claim 5 , wherein said agent is selected from the group consisting of 1,1,1,3,3,3 hexafluoro-2-propanol (HFIP), trifluoroethanol (TFE), and trifluoroacetic acid (TFA). 
     
     
         7 . The method of  claim 5 , wherein said solvent is selected from the group consisting of sodium hydroxide, potassium hydroxide, ammonium hydroxide, and dimethyl sulfoxide. 
     
     
         8 . The method of  claim 5 , wherein said anionic surfactant is selected from the group consisting of Sodium dodecyl sulfate (SDS), Ammonium lauryl sulfate, Docusate sodium salt, N-Lauroylsarcosine sodium salt, Lithium dodecyl sulfate, 1-Octanesulfonic acid sodium salt, Sodium 1-butanesulfonate, Sodium hexanesulfonate, Chenodeoxycholic acid, Dehydrocholic acid, Glycocholic acid and Sodium deoxycholate. 
     
     
         9 . An isolated antibody which binds with a higher affinity to oligomers of human Islet Amyloid Polypeptide (IAPP) than fibrils of human IAPP. 
     
     
         10 . The isolated antibody of  claim 9 , attached to an identifiable moiety. 
     
     
         11 . The isolated antibody of  claim 9 , being a polyclonal antibody. 
     
     
         12 . The isolated antibody of  claim 9 , being a monoclonal antibody. 
     
     
         13 . The isolated antibody of  claim 9  being formulated in a pharmaceutical composition. 
     
     
         14 . A method of detecting IAPP oligomers in a biological sample, the method comprising contacting the biological sample with the antibody of  claim 9  under conditions which allow formation of immunocomplexes, wherein a presence of immunocomplexes above a predetermined threshold is indicative of IAPP oligomers in the biological sample. 
     
     
         15 . A method of diagnosing diabetes in a subject in need thereof, the method comprising detecting IAPP oligomers in a biological sample of the subject, wherein a presence or level above a predetermined threshold of said IAPP oligomers in said biological sample, is indicative of diabetes in the subject. 
     
     
         16 . The method of  claim 15 , wherein said detecting is effected using an antibody which binds with a higher affinity to oligomers of human Islet Amyloid Polypeptide (IAPP) than fibrils of human IAPP. 
     
     
         17 . A method of treating diabetes in a subject in need thereof, the method comprising administering to the subject a therapeutic effective amount of an agent which reduces the activity or amount of an IAPP oligomer, thereby treating diabetes in the subject. 
     
     
         18 . The method of  claim 17 , wherein said agent is an antibody which binds with a higher affinity to oligomers of human Islet Amyloid Polypeptide (IAPP) than fibrils of human IAPP. 
     
     
         19 . A method of identifying an agent useful for treating diabetes, the method comprising contacting the agent with the composition of matter of  claim 1 , wherein a down-regulation of an amount or activity of said oligomers is indicative of an agent useful for the treatment of diabetes. 
     
     
         20 . The method of  claim 19 , wherein the agent is a small molecule or an antibody. 
     
     
         21 . The method of  claim 19 , wherein said contacting is effected in the presence of cells. 
     
     
         22 . A vaccine comprising the composition of matter of  claim 1  and an immunologically acceptable carrier. 
     
     
         23 . A method of treating diabetes in a subject in need thereof, the method comprising administering to the subject an effective amount of the vaccine of  claim 22 , thereby treating diabetes in the subject.