Sickle cell disease: combination new therapies vs. CRISPR-Cas9 potential and challenges - review article

Abstract

In 2022, sickle cell disease (SCD) continues to affect the lives of millions of people, being one of the most frequently inherited blood disorders worldwide. Recently, several new therapies have been FDA approved for the treatment of SCD. The complexity of the pathophysiology of sickling has given opportunity to the evolution of several modalities of therapies. Nonetheless, the potential for complementary targeting of HbS polymerization, vasocclusion, and other inflammatory pathways remains controversial. None of these drugs can be considered a single curative line of treatment. With the advancement of CRISPR/Cas9 technology, autologous transplant of gene-edited hematopoietic stem cells could possibly provide a cure for most patients with SCD. The advantage of this approach over the conventional stem cell transplantation is that it decreases the need for immuno-suppressive drugs and the risk of graft-versus-host disease. In addition, recent technological advances can reduce the off-target effects, but long-term monitoring is needed to ensure the reliability of these methods in the clinical setting. This review explores the efficacy and safety of combination therapies and contrasting this alternative with the challenges that exist with sickle cell gene therapy using CRISPR.

Keywords: CRISPR; Crizanlizumab; L-Glutamine; Pyruvate kinase inhibitor; Sickle cell disease; Voxelotor.