New insights into sickle cell disease: mechanisms and investigational therapies

Sickle cell disease (SCD) afflicts millions worldwide. The simplicity of its single nucleotide mutation belies the biological and psychosocial complexity of the disease. Despite only a single approved drug specifically for the treatment of SCD, new findings reviewed from 2015 provide the direction forward.

The last year has provided a wealth of support for mechanisms affecting the red cell, hemolysis and vasculopathy, the innate immune system activation, blood cell and endothelial adhesiveness, central sensitization to pain, and chronic brain injury. The evidence supporting expanded use of hydroxyurea continues to mount. Many promising therapies are reaching clinical trial, including curative therapies, with more on the horizon.

Evidence is compelling that the use of hydroxyurea must be expanded by clinicians to gain the full pleiotropic benefits of this approved drug. Clinicians must become aware that severe acute and chronic pain has a biological and neurologic basis, and the understanding of this basis is growing. Researchers are testing investigational therapies at an unprecedented pace in SCD, and partnership between patients, researchers, and the private sector provides the most rapid and productive way forward.