Are genetic approaches still needed to cure sickle cell disease?

摘要

Sickle cell disease (SCD) is a heritable disorder of hemoglobin that affects 1 of every 400 black newborns and approximately 100,000 persons in the United States (1). This disease burden has a considerable impact on individuals affected and on health care systems. In the United States alone, the medical cost of caring for patients with SCD exceeds $1 billion annually. SCD is caused by a point mutation in codon 6 of the β-globin chain that results in an amino acid substitution of valine for glutamic acid, and promotes the formation of long hemoglobin polymers under hypoxic conditions. This abnormal polymerization deforms erythrocytes and causes significant alterations in red cell integrity, rheologic properties, and lifespan. SCD leads to chronic hemolysis and a vasculopathy that involves virtually every organ. Most adults and many children develop a chronic, debilitating condition, leading to high rates of disability and unemployment. A current cohort of adults that were followed and treated with disease-modifying therapy at two large academic medical centers had a median survival of 48 years (2), which is not much different when compared with a NIH-sponsored multicenter, prospective study of a cohort of adults with SCD that was published 25 years ago (3).