SOLUBLE AND CELL-ASSOCIATED HEMOJUVELINS AS A THERAPY AND DIAGNOSTIC FOR IRON METABOLISM DISEASES

SOLUBLE AND CELL-ASSOCIATED HEMOJUVELINS AS A THERAPY AND DIAGNOSTIC FOR IRON METABOLISM DISEASES

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BACKGROUND: Various diseases of iron metabolism are caused by abnormal hepcidin production, either too much or too little. In the case of anemia of inflammation, the production of hepcidin is stimulated by various cytokines including IL-6. Increased hepcidin levels cause the loss of ferroportin from the surfaces of macrophages engaged in the recycling of iron from senescent red cells. As a result, iron is trapped in macrophages and blood iron concentration decreases, restricting the flow of iron to the bone marrow, and thus slowing the production of hemoglobin and consequently decreasing the production of erythrocytes. In another iron metabolism disease, juvenile hemochromatosis (JH), the decreased expression of hepcidin, is the result of the mutations in the HJV gene. The decreased expression of hepcidin results in severe iron overload.

INNOVATION: Researchers at UCLA have shown that cellular hemojuvelin positively regulates hepcidin mRNA expression, independent of the IL-6 pathway by using hemojuvelin-specific siRNAs to vary hemojuvelin mRNA concentration. From these hemojuvelin studies, UCLA researchers have developed a recombinant soluble form of hemojuvelin (rs-hemojuvelin) and found in blood a naturally occurring soluble form of hemojuvelin, s-hemojuvelin. The recombinant rs- hemojuvelin was shown to inhibit hepcidin production in primary human hepatocytes in a dose-dependent manner. These researchers also found that hemojuvelin with a glycosylphosphatidylinositol-linked membrane anchor (GPI-hemojuvelin) induces hepcidin production thereby decreasing iron levels.

POTENTIAL APPLICATIONS: rs-hemojuvelin may be used to treat iron disorders that are dependent on hepcidin concentration. Researchers have shown in hepatocytes that rs-hemojuvelin could be administered parenterally to treat anemia of inflammation by inhibiting hepcidin production and releasing iron from sequestration. The increased level of iron stimulates erythrocyte production and thus reverses anemia. GPI-hemojuvelin, rs-hemojuvelin, and s-hemojuvelin, may also be used in assays to monitor or diagnose diseases of iron metabolism.

Reference: UCLA Case No. 2005-604 US Patent Application: 11/427,095

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