Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin

• US 7,534,764 B2
• Filed: 06/28/2006
• Issued: 05/19/2009
• Est. Priority Date: 06/29/2005
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California), Xenon Pharmaceuticals Inc.
• Original Assignee: Regents of the University of California (University of California), Xenon Pharmaceuticals Inc.
• Inventors: Lin, Lan, Goldberg, Yigal P., Ganz, Tomas
• Primary Examiner(s): Monshipouri; Maryam
• Application Number:
  US11/427,095
• Publication Number:
  US 20070004618A1
• Time in Patent Office: 1,056 Days
• Field of Search: 514/12
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/1709 from mammals
• 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 3/02 Nutrients, e.g. vitamins, minerals

Abstract

Disclosed herein are hemojuvelin-specific siRNAs that vary hemojuvelin mRNA concentration. Also disclosed herein, GPI-hemojuvelin positively regulated hepcidin mRNA expression, independently of the IL-6 pathway, whereas soluble hemojuvelin (s-hemojuvelin) suppressed hepcidin mRNA expression in primary human hepatocytes in a log-linear dosedependent manner. Disclosed are compositions and methods for modulating diseases of iron metabolism and hepcidin expression or hepcidin levels.

Claims

1. A method of treating, a disease of iron metabolism in a mammalian subject diagnosed as having the disease of iron metabolism which comprises administering to the mammalian subject a therapeutically effective amount of at least one mammalian soluble hemojuvelin protein.

2. The method of claim 1, wherein the soluble hemojuvelin protein lacks its glycophosphatidylinositol anchor.

3. The method of claim 1, wherein the soluble hemojuvelin protein consists of SEQ ID NO:

1.

4. The method of claim 1, wherein the disease of iron metabolism is anemia of chronic disease, juvenile hemochromatosis, adult onset hemochromatosis, iron overload, and iron deficiency anemia.