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Novel small molecule therapy shows benefit for anemic patients via hydration of red blood cells
Date:2/5/2008

WASHINGTON, February 5, 2008 Researchers are identifying innovative therapeutics for sickle cell anemia that focus on specific factors in the disease's progression, such as the important role of hydration of the red blood cells. According to a study prepublished online in Blood, the official journal of the American Society of Hematology, a novel small molecule therapy called senicapoc showed efficacy in maintaining hydration of red blood cells and increasing hemoglobin levels in patients with sickle cell anemia. Sickle cell anemia affects about 70,000 Americans, and millions worldwide.

Sickle cell anemia (the most common form of sickle cell disease, or SCD) is a serious chronic condition in which the red blood cells (RBCs) can become sickle-shaped upon deoxygenation (shaped like a "C"). Because of their shape, rigidity, and tendency to stick to blood vessel walls, the cells do not move easily through the vessels and can form clumps, which may lead to blocked blood flow and pain, infections, or organ damage. Research suggests that dehydration of the RBCs is one of the key contributors to the deformed shape and affects the levels of circulating hemoglobin, an important determinant of oxygen delivery throughout the body. The dehydration appears to result from loss of potassium via two pathways, one of which is known as the Gardos channel. It has been suggested that a therapy designed to block this channel might have a beneficial effect on the progression of the disease.

Senicapoc, a known Gardos channel blocker, works by limiting solute and water loss, thereby preserving RBC hydration. Previous studies have shown that senicapoc prevents the loss of potassium from the RBCs, is well tolerated, and has favorable pharmacokinetics with a long half-life, permitting once-daily dosing.

In a 12-week, multicenter, phase II, randomized, double-blind, dose-finding study, senicapoc was evaluated for its effect on hemoglobin level and mark
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Contact: Laura Stark
lstark@hematology.org
202-776-0544
American Society of Hematology
Source:Eurekalert

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