Methods of Treating Sickle Cell Disease

Abstract

The present invention relates to methods of treating sickle cell disease comprising reducing, in a subject in need of such treatment, the adherence between sickle RBCs and leukocytes. It is based, at least in part, on the discovery that leukocytes play a direct role in the initiation of venular occlusion. The present invention further provides for methods for identifying agents which decrease SS-RBC/leukocyte adherence and for animal models which may be used to further elucidate the mechanism of vaso-occlusion in sickle cell crises.

What is claimed is: 
     
         1 . A method of treating a sickle cell disease subject in vaso-occlusive crisis comprising administering to the subject an E-selectin inhibitor that interacts with a calcium-binding lectin domain of E-selectin in an amount effective to reduce the adherence of sickled red blood cells to leukocytes, so as to thereby treat the subject. 
     
     
         2 . A method of reducing the adherence of sickled red blood cells to leukocytes in a sickle cell disease subject in vaso-occlusive crisis comprising administering to the subject an E-selectin inhibitor that interacts with a calcium-binding lectin domain of E-selectin in an amount effective to reduce the adherence of sickled red blood cells to leukocytes in the subject. 
     
     
         3 . A method of reducing the pain of a sickle cell crisis in a sickle cell disease subject comprising administering an E-selectin inhibitor that interacts with a calcium-binding lectin domain of E-selectin in an amount effective to reduce the subject's pain. 
     
     
         4 . A method of alleviating thesymptoms of a vaso-occlusive crisis in a subject with sickle cell disease comprising administering to the subject an E-selectin inhibitor that interacts with a calcium-binding lectin domain of E-selectin in an amount effective to alleviate the symptoms. 
     
     
         5 . A method of alleviating pain caused by a vaso-occlusive crisis in a subject with sickle cell disease comprising administering to the subject an E-selectin inhibitor that interacts with a calcium-binding lectin domain of E-selectin in an amount effective to alleviate the subject's pain.