Advances and Challenges in the Treatment of Sickle Cell Disease Using Gene Therapy

Abstract

Sickle cell disease (SCD) is a hereditary blood disorder that affects nearly 8 million people worldwide and causes abnormal hemoglobin production. Furthermore, SCD worsens quality of life through chronic anemia and vaso-occlusive events, reducing life expectancy. Non-curative treatments have been established to help manage the symptoms of SCD, while curative therapies such as allogeneic hematopoietic stem cell transplantation face limitations due to a lack of donor availability and complications from graft rejection. In recent years, early phase clinical trials have been conducted to analyze the efficacy and safety of using new gene editing based technologies, such as CRISPR, as alternative cures for SCD. This paper will assess these advances with a focus on autologous hematopoietic stem cell-based gene therapies including exagamglogene autotemcel and lovotibeglogene autotemcel. Clinical studies have found that these therapies are able to consistently stabilize patient’s hemoglobin levels and effectively reduce vaso-occlusive events. Despite these successes, continued research is necessary to monitor the long-term safety of the different forms of gene therapy, address their high costs and limited accessibility, and further improve the safety of their pre-conditioning processes.