Targeting P-selectin ligands: ushering in a new treatment paradigm for Sickle Cell Disease
- Hematology & Transfusion International Journal
Dr. Ashraf Abdullah Saad, MBBS, MRCPCH
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Sickle cell disease (SCD) is a debilitating systemic disease with limited treatment options for disease-related complications. Microvascular vaso-occlusion is the hallmark of the disease with profound morbidity and increased mortality. Vaso-occlusion underlies intricate pattern of complications related to hyper-adhesiveness of circulating blood cells and endothelium. Over-expression of P-selectin is central to initiation of the vaso-occlusive cascade by downstream engagement of multiple adhesion receptor/ligand pairs. Blocking P-selectin has been shown to effectively prevent vaso-occlusion by blocking these adhesive interactions. However, the model of the E-selectin inhibitor uproleselan in acute myeloid leukemia (AML) should instigate the development of similar agents that target selectinligand adhesive interactions in order to attenuate the clinical effects of vaso-occlusion. Interestingly, the sialylated and fucosylated tetrasaccharide sialyl Lewis(X) (sLeX) was found to be the glycan (carbohydrate) determinant for selectin binding. Therefore, novel synthetic lectins that target glycan determinants on P-selectin-ligands could prove more precise and efficient drugs, not only for prevention, but also for treating patients with vasoocclusion crises (VOCs).
vaso-occlusion, p-selectin, crizanlizumab, psgl-1, slex, artificial lectins