Methods for identifying compounds for the treatment of type 1 diabetes

• US 8,030,288 B2
• Filed: 08/22/2008
• Issued: 10/04/2011
• 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
• Primary Examiner(s): WHITEMAN, BRIAN A
• Application Number:
  US12/196,536
• Publication Number:
  US 20090081201A1
• Time in Patent Office: 1,138 Days
• Field of Search: 514/44, 424/184.1
• US Class Current: 514/44.00A
• 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 limiting pancreatic β

cell apoptosis comprising administering to a patient with type I diabetes an amount effective of an inhibitor of human apoCIII to reduce apoCIII-induced increase in intracellular calcium concentration in pancreatic β

cells, wherein the 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.

2. The method of claim 1 wherein the patient has an increased blood serum level of human apoCIII.

3. The method of claim 1, wherein the patient has an increased blood serum level of sialylated human apoCIII.

4. The method of claim 1, wherein the inhibitor is an apoCIII-selective antibody.

5. The method of claim 1, wherein the inhibitor is an antisense oligonucleotide directed against the apoCIII mRNA.

6. The method of claim 1, wherein the inhibitor is a small interfering RNA directed against the apoCIII mRNA.