ApoIII and the Treatment and Diagnosis of Diabetes

• US 20140220039A1
• Filed: 03/21/2014
• Published: 08/07/2014
• Est. Priority Date: 04/29/2003
• Status: Active Grant

• Current Assignee: Biocrine AB (BioStratum, Inc.)
• Original Assignee: Biocrine AB (BioStratum, Inc.)
• Inventors: BERGGREN, Per-Olof
• Granted Patent: US 9,169,484 B2
• Time in Patent Office: Days
• US Class Current: 424/172.1
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: G01N 2333/775 Apolipopeptides
• CPC Class Codes: G01N 2440/38 addition of carbohydrates, e.g. glycosylation, glycation
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 30/02 Column chromatography
• CPC Class Codes: G01N 33/5041 involving analysis of members of signalling pathways
• CPC Class Codes: G01N 33/507 Pancreatic cells
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

The present invention provides methods of identifying candidate compounds for the treatment of type I diabetes comprising contacting pancreatic β cells with an amount of apolipoprotein CIII (“apoCIII”) effective to increase intracellular calcium concentration, in the presence of one or more test compounds, and identifying those test compounds that inhibit an apoCIII-induced increase in intracellular calcium concentration in the pancreatic β cells. The present invention also provides methods for treating patients with type I diabetes comprising administering to the patient an amount effective of an inhibitor of apoCIII to reduce apoCIII-induced increase in intracellular calcium concentration in pancreatic β cells.

Claims

1. A method for treating diabetes, comprising (a) comparing an amount of apoCIII in a blood serum sample from a diabetic subject and comparing it to a control blood serum sample;

(b) identifying those subjects with an elevated amount of apoCIII in the blood serum sample relative to the control blood serum sample as candidate subjects; and

(c) treating the candidate subject with an amount effective of an apoCIII inhibitor to treat the diabetes.

2. The method of claim 1, wherein the apoCIII amount is an amount of sialylated apoCIII.

3. The method of claim 2, wherein the sialylated apoCIII is mono-sialylated apoCIII.

4. The method of claim 2, wherein the sialylated apoCIII is di-sialylated apoCIII.

5. The method of claim 2, wherein the sialylated apoCIII is both mono- and di-sialylated apoCIII.

6. The method of claim 1, wherein the apoCIII inhibitor is selected from the group consisting of an apoCIII-selective antibody, an antisense oligonucleotide directed against the apoCIII mRNA, and a small interfering RNA directed against the apoCIII mRNA.

7. The method of claim 6 wherein the apoCIII inhibitor comprises an apoCIII-selective antibody.

8. The method of claim 6 wherein the apoCIII inhibitor comprises an antisense oligonucleotide directed against the apoCIII mRNA.

9. The method of claim 6 wherein the apoCIII inhibitor comprises a small interfering RNA directed against the apoCIII mRNA.