Plugging the Leak in Sickle Cells

Hemolytic anemia in patients with sickle cell disease is attributed to leakage of solute and water from erythrocytes, which leads to cellular dehydration, hemoglobin S polymerization, irreversible sickling, and trapping of red cells in the microcirculation. Such cellular dehydration results largely from dysregulated flow of potassium through the Gardos channel, a calcium-activated membrane-transport channel. Researchers have shown that clotrimazole inhibits the Gardos channel and prevents dehydration of sickle erythrocytes (J Clin Invest 1993; 92:520).

Now, investigators have conducted an industry-funded phase II trial of senicapoc — a long-acting Gardos-channel blocker that inhibits potassium efflux — to assess its effect on hemoglobin leve…