European Journal of Biomedical and Pharmaceutical Sciences

DEVELOPMENT OF EFFECTIVE THERAPIES IN SICKLE CELL DISEASE

Ghazala Nathu*, Saahil Patel and Adila Nathu

ABSTRACT

Recent advances in managing Sickle Cell Disease (SCD) improved the survival of pediatric patients and the quality of life in adult patients significantly. Disease-modifying drug therapies hydroxyurea, voxelotor, crizanlizumab, and L-glutamine reduced pain crises and severe complications. Allogeneic hematopoietic stem cell transplantation using sibling donors is currently the only standard curative option. However, the matched-related donor is available for a smaller proportion of patients. Cord blood transplantation and haploidentical transplantation with a modified conditioning regiment are expanding the allogeneic donor pool making the therapy available to most patients. In vitro expanded cord blood cells are effectively used in adult patients. However, the most promising treatment for a cure is gene therapy. Several gene therapy methodologies have been successful in recent clinical trials. A new non-sickling allele can be introduced to hematopoietic stem cells by lentiviral vectors. The sickle allele could be silenced while enhancing other hemoglobin alleles, most notably HgbF. The sickle allele could be gene-edited through homologous-directed repair and CRISPR technology. Editing regulatory sequences boost non-sickle hemoglobin production. Multidisciplinary expertise and effort are combined to standardize metrics and compare different therapeutic options. The Cure Sickle Cell Initiative supports research development encompassing pharmacologic, biotherapies, and genetic advancements. The workgroups are bringing together basic and translational researchers, clinicians, and patients through education and motivation in a joint effort to support high-quality clinical trials toward curative therapies.

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