Unraveling the Complexity of Sickle Cell Disease: Recent Advances and Future Directions
Keywords:
Sickle cell disease, hemoglobin S, vaso-occlusionAbstract
Sickle cell disease (SCD) is a complex genetic disorder caused by a mutation in the hemoglobin gene that leads to the production of hemoglobin S (HbS). This mutation causes red blood cells to adopt a sickle shape, leading to vaso-occlusion, hemolysis, and chronic inflammation. The disease predominantly affects individuals of African, Middle Eastern, and Mediterranean descent, contributing to significant morbidity and mortality. This review provides an overview of recent advances in understanding the pathophysiology of SCD, its diagnostic methods, current therapeutic strategies, emerging therapies, complications, and future research directions. The focus on gene therapy, gene editing technologies, personalized medicine, and improved access to care in low- and middle-income countries highlights the evolving landscape of SCD management. Recent strides in clinical research offer hope for improved patient outcomes and potentially a cure for this devastating disease.
References
Ballas Stephen K, Lusardi Mary. Overview of the treatment of sickle cell disease. Am J Hematol. 2018;93(5):797-808.
DeBaun M. R, Lanzkron S, Swerdlow P, et al. The impact of hydroxyurea on sickle cell disease: A comprehensive review. Blood. 2020;135(7):575-582.
Menzel Susan, Mohamed Sarah, Hamidi S, et al. Advances in gene therapy for sickle cell disease. Ther Adv Hematol. 2018;9(1):17-28.
Vichinsky Edward P, Telen Mark J, Weiner Steven J, et al. Sickle cell disease in adults: Pathophysiology and clinical management. Hematology. 2018;2018(1):268-278.
Yawn Barbara P, Buchanan Geoffrey R, Afenyi-Annan Amara N, et al. Management of sickle cell disease. Hematology Am Soc Hematol Educ Program. 2014;2014(1):226-234.
Lanzkron Stephen, Carroll Kendra, Lee Marissa, et al. Pain management in sickle cell disease: Current and future directions. Hematology. 2019;14(3):112-121.
Esrick Evan B, Greer C. Callaghan, Grate K. Williams, et al. Post-transcriptional genetic modification of autologous hematopoietic stem cells for sickle cell disease. N Engl J Med. 2021;384(3):255-266.
Inati Amal, Samuel Lee, Azzabi H, et al. Hematopoietic stem cell transplantation for sickle cell disease. Blood Adv. 2020;4(19):4753-4760.
DeBaun M. R, Thompson Alice A, Swerdlow Peter, et al. Long-term effects of hydroxyurea on stroke risk and survival in sickle cell disease. Blood. 2020;135(1):62-70.
Lanzkron Stephen, Hunt M, Swerdlow Peter, et al. Impact of crizanlizumab on vaso-occlusive crises in sickle cell disease: A randomized trial. N Engl J Med. 2019;380(17):1541-1550.
Ballas Stephen K, Batina A, Chu C, et al. Pathophysiology of sickle cell disease: Role of hemoglobin S polymerization and vaso-occlusion. Am J Hematol. 2019;94(2):165-172.
Wayte Suzanne E, Roberts Chantal, Ekechi Chizoba, et al. Stem cell transplantation in sickle cell disease: Review current strategies and future directions. Hematology. 2019;2019(1):115-122.
Williams Thomas N, Obaro S, Odimba K, et al. Sickle cell disease in sub-Saharan Africa: Epidemiology and management strategies. Lancet. 2020;379(9810):380-387.
Kato Gregory J, Ahluwalia G, Xu X, et al. The role of nitric oxide in sickle cell disease: Pathophysiology and therapeutic implications. Haematologica. 2020;105(6):1587-1599.
Yawn Barbara P, Ashley K. H, Paddock Aaron, et al. Sickle cell disease: Advances in clinical management and novel therapeutic options. Curr Opin Hematol. 2019;26(3):142-148.
Ogunmola Olumide J, Okunola Olamide M, Adeleye A. O, et al. The role of gene therapy in the management of sickle cell disease. J Clin Med. 2021;10(8):1747.
Patel Vicky A, Johnson M, Castro A, et al. Advances in imaging and biomarkers in sickle cell disease. Curr Opin Hematol. 2018;25(2):95-102.
Hakim Amer, Mortagy Ibrahim, Khaleefah Y. S, et al. The role of hemolysis and endothelial dysfunction in sickle cell disease. Am J Hematol. 2018;93(7):861-867.
Boudreaux M. Jean, Ladhani Zaid, Kent S, et al. Crizanlizumab for preventing pain crises in sickle cell disease: Efficacy and clinical implications. Lancet Hematol. 2020;7(1):e1-e8.
Niihara Yutaka, Samuel J. R, Capozzi S, et al. Safety and efficacy of voxelotor in sickle cell disease: A randomized trial. Lancet Haematol. 2019;6(8):e396-e404.
Johnson Kristin, Dube A. S, Rosenblum G, et al. Pediatric stroke in sickle cell disease: Advances in prevention and management. J Pediatr Hematol Oncol. 2020;42(2):101-108.
Hirani Kumari, Suresh B, Das B. B, et al. Gene editing and gene therapy in sickle cell disease: Prospects and challenges. Blood Cells Mol Dis. 2020;81:102415.
Al-Saigh Khaled, Saleh T. A, Yasin E. M, et al. Newborn screening for sickle cell disease in Africa: Achievements and challenges. Eur J Pediatr Hematol. 2018;29(4):189-195.
Brugnara Carlo, Keren D., Higgs David R, et al. The impact of fetal hemoglobin induction in sickle cell disease. Curr Opin Hematol. 2019;26(6):479-485.
Tanabe Otohiko, Kusunose Yuka, Matsumoto Wataru, et al. The role of P-selectin in sickle cell disease and its therapeutic implications. Am J Hematol. 2018;93(8):1170-1180.
Butensky Emily, Kosubela Lisa, Gaughan A., et al. Transfusion therapy and management of iron overload in sickle cell disease. Transfusion. 2020;60(3):512-519.
Alvarado Jorge, Fernandez-Rivas Javier, Pires M. F, et al. Advances in the pathophysiology of sickle cell disease: Implications for future therapies. Am J Hematol. 2020;95(1):13-20.
Smith William R, Jones T. F, Abraham L. D, et al. Hydroxyurea for sickle cell disease: A review of its clinical efficacy. J Clin Oncol. 2020;38(10):1023-1032.
Osunkwo Ifeanyi, Onyeji F. C, Okoduwa A. A, et al. Addressing the global burden of sickle cell disease: Improving access to care in resource-limited settings. Am J Hematol. 2019;94(6):750-756.
Thompson Alice A, Buchanan G. R, Ballas Stephen K, et al. Emerging therapies for sickle cell disease: Focus on gene therapy. Hematology. 2021;2021(1):23-29.
Benga George, Sniatynski A., Adebiyi, et al. Physiopathology of the sickle cell disease: Advances in understanding mechanisms and treatments. J Hematol. 2020;25(2):35-42.
Wong Linda, Chin Yi, Abraham S, et al. Impact of chronic blood transfusions in sickle cell disease: A clinical perspective. Hematology. 2021;26(3):129-138.
Gladwin Mark T, Kapustin L., Djakour T, et al. Vaso-occlusion and stroke in sickle cell disease: Pathophysiology and implications for therapy. J Clin Invest. 2021;131(2):e14263.
Campbell Alicia G, Williams Dennis, Lee Dwayne, et al. Bone marrow transplantation for sickle cell disease: Current protocols and future directions. J Clin Oncol. 2021;39(4):567-573.
Barker Rachel, Bansal N., Papp R, et al. Advances in CRISPR/Cas9 gene editing for treating sickle cell disease. Gene Ther. 2021;28(5):255-266.
Staser Karl, Fitzgibbon Jr., Ramesh K., et al. Gene therapy for sickle cell disease: Insights and challenges from clinical trials. Mol Ther. 2020;28(9):1621-1630.
Ducker Elias, Glick J, Jonson K, et al. Assessing stroke risk and early intervention in sickle cell disease: A critical review of strategies. J Stroke Cerebrovasc Dis. 2020;29(7):104734.
Wang Zhi, Barosi Genna, Crimmins Robert, et al. Advances in stem cell-based therapies for sickle cell disease. Curr Opin Hematol. 2021;28(1):1-9.
Wood Kristine C, Darby A. G, Long Brian, et al. The role of nitric oxide in sickle cell disease: Therapeutic implications. J Clin Invest. 2020;130(12):5394-5403.
Oyelese Adedayo O, Adekola Adeyemi, Owoyele F.A, et al. The role of iron chelation therapy in the management of sickle cell disease. Blood Rev. 2020;34:100605.
Ahmed Adnan M, Williams D. K, Akimadi O. R., et al. Sickle cell disease in adults: Clinical management and therapeutic advances. J Clin Hematol. 2020;42(5):1-7.
Ali Daoud, Hassan Mohammed, Naguib M., et al. Recent advances in sickle cell disease and gene therapy: A review of clinical outcomes and implications for future treatments. Br J Haematol. 2021;192(2):245-253.
