Came across interesting article on new treatment options currently under research @ Weill Cornell Medical College, listed below are few excerpts:
Two studies led by investigators at Weill Cornell Medical College shed light on the molecular biology of three blood disorders, leading to novel strategies to treat these diseases.
The two new studies— one published online by Nature Medicine and the other in the online edition of the Journal of Clinical Investigation— propose two new treatments for beta-thalassemia, a blood disorder which affects thousands of people globally every year. In addition, they suggest a new strategy to treat thousands of Caucasians of Northern European ancestry diagnosed with HFE-related hemochromatosis and a novel approach to the treatment of the rare blood disorder polycythemia vera.
These research insights were only possible because two teams that included 24 investigators at six American and European institutions decoded the body's exquisite regulation of iron, as well as its factory-like production of red blood cells.
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Iron control is regulated, first and foremost, by hepcidin or Hamp, a hormone secreted into the bloodstream by the liver. Hamp controls the so-called "iron gate" in the intestines, a protein known as ferroportin. Ferroportin allows the body to absorb iron from food to help make red blood cells. (Iron latches on to the oxygen that the blood cells carry.) If iron levels are too high from iron-rich foods that are consumed, Hamp levels increase, which shuts the door on ferroportin's iron gate, blocking iron absorption, said Weill Cornell's Dr. Carla Casu, a postdoctoral researcher in Rivella's laboratory and one of the two lead authors of this study with Guo at Isis Pharmaceuticals.
Patients with beta-thalassemia and hemochromatosis have levels of Hamp that are too low, so the body 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," said 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 morfe 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," Monia said.
The research team leaders, Monia and 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 said.
Both potential therapies offer new solutions to old blood disorder diseases. They need more studies before they can be brought to the clinic, although the antisense technology can be rapidly modified for its applications in humans, Rivella said.
Full Article:
http://www.biosciencetechnology.com/news/2013/03/decoding-biology-blood-disorders-leads-new-therapies