Blocking HbS Polymerization in SCD

Treating sickle cell disease by targeting HbS polymerization.

Although the root cause of sickle cell disease is the polymerization of hemoglobin S (HbS) to form fibers that make red cells less flexible, most drugs currently being assessed in clinical trials are targeting the downstream sequelae of this primary event. Less attention has been devoted to investigation of the multiple ways in which fiber formation can be inhibited. In this article, we describ...

Cytochalasins inhibit nuclei-induced actin polymerization by blocking filament elongation

Polylysine was found to induce polymerization of muscle actin in a low ionic strength buffer containing 0.4 mM MgCl2. The rate of induced polymerization was dependent on the amount and on the molecular size of the polylysine added. A similar effect was obtained by adding actin nuclei (containing about 2-4 actin subunits) cross-linked by p-N,N'-phenylenebismaleimide to G-actin under the same con...

Aptamer therapy for SCD?

In this issue of Blood, Gutsaeva et al describe an aptamer with high affinity for murine P-selectin and its efficacy in preventing vaso-occlusion in a mouse sickle cell disease (SCD) model.1 Each year, more than 200 000 children are born with SCD,2 yet there is a paucity of treatment options available for sufferers.3 The disease is caused by homozygous expression of a mutation in the beta globi...

Specificity control in solid-phase enzyme immunoassay for HBsAg by one-step in situ blocking with human anti-HBs.

GBT440 Inhibits Sickling of Sickle Cell Trait Blood Under In Vitro Conditions Mimicking Strenuous Exercise

In sickle cell trait (SCT), hemoglobin A (HbA) and S (HbS) are co-expressed in each red blood cell (RBC). While homozygous expression of HbS (HbSS) leads to polymerization and sickling of RBCs resulting in sickle cell disease (SCD) characterized by hemolytic anemia, painful vaso-occlusive episodes and shortened life-span, SCT is considered a benign condition usually with minor or no complicatio...