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Comment
. 2008 Apr 15;111(8):3918-9.
doi: 10.1182/blood-2008-01-135350.

Gardos pathway to sickle cell therapies?

Clinton H Joiner  1
Affiliations
Comment

Gardos pathway to sickle cell therapies?

Clinton H Joiner. Blood. .

Abstract

In this issue of Blood, Ataga and colleagues report that treatment of sickle cell disease patients with senicapoc, a Gardos channel inhibitor, reduces the number of dehydrated cells, increases hemoglobin levels, and diminishes hemolysis.

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Conflict of interest statement

Conflict-of-interest disclosure: C.H.J. participated as a site investigator in the phase 3 trial of senicapoc, funded by Icagen (Durham, NC)/McNeil (Fort Washington, PA). He has been a paid consultant for Icagen. ■

Figures

None
Transport pathways contributing to sickle cell dehydration. Hemoglobin (Hb) S polymerization activates the sickling-induced pathway, permitting Ca++ entry. Increased cytoplasmic Ca++ activates the Gardos pathway, which mediates rapid K+ efflux, balanced by Cl− exit via a chloride conductance pathway. High Hb S concentration resulting from abnormal regulation of K:Cl cotransport may potentiate Hb S polymerization in reticulocytes. Once initiated, the vicious cycle of sickling and dehydration intensifies and perpetuates itself. KCC indicates K:Cl cotransporter; SIP, sickling-induced pathway; G, Gardos pathway; and CC, Cl conductance pathway.
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