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Researchers decode biology of blood and iron disorders mapping out novel future therapies
Date:3/25/2013

ody absorbs more iron than is healthy. Hemochromatosis occurs because of a deficit in the HFE gene that controls the Hamp hormone. "Hamp is sleeping. It doesn't wake up when iron comes along, so too much iron is absorbed," says Dr. Rivella. The defect in beta-thalassemia is due to a defect in the globin gene that helps make hemoglobin. So Hamp is shut down because the body senses the anemia, and believes that more iron is required to make red cells. As a result, there is iron overload."

The researchers found an answer to the iron overload in both diseases by studying a third disease, a childhood disorder in which a mutation in a gene called Tmprss6 causes Hamp levels to rise too high, so not enough iron is being extracted from the diet. Tmprss6 keeps Hamp levels high during childhood and adolescence, so a body cannot use iron successfully to grow.

They reasoned that if they could create the conditions of Tmprss6 mutation -- high levels of Hamp hormone and repression of the body's use of iron -- in patients with thalassemia and hemochromatosis, they could treat those conditions. "If we block Tmprss6, we increase the expression of Hamp to normal levels, with the consequence that iron does not now accumulate," Dr. Monia says.

The research team leaders, Dr. Monia and Dr. Guo at Isis Pharmaceuticals, developed an antisense drug that blocked Tmprss6 "in order to wake up Hamp expression." An antisense drug works by administering a chemically modified, stable DNA-like molecule that targets specifically an RNA sequence that is produced by the gene. This sequence binds to the natural gene RNA product, forming a double-stranded RNA/DNA hybrid duplex. This duplex is recognized by enzymes in the cell that cause degradation of the natural RNA. "When you destroy that RNA, you destroy the ability of the Tmprss6 to make any protein," Dr. Monia says.

Both potential therapies offer new solutions to old blood disorder diseases. They need more studies
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Contact: Lauren Woods
Law2014@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

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