Recent Advances in the Treatment of Sickle Cell Disease

Abstract

Sickle cell anemia (SCA) was first described in the Western literature more than 100 years ago. Elucidation of its molecular basis prompted numerous biochemical and genetic studies that have contributed to a better understanding of its pathophysiology. Unfortunately, the translation of such knowledge into developing treatments has been disproportionately slow and elusive. In the last 10 years, discovery of BCL11A, a major γ-globin gene repressor, has led to a better understanding of the switch from fetal to adult hemoglobin and a resurgence of efforts on exploring pharmacological and genetic/genomic approaches for reactivating fetal hemoglobin as possible therapeutic options. Alongside therapeutic reactivation of fetal hemoglobin, further understanding of stem cell transplantation and mixed chimerism as well as gene editing, and genomics have yielded very encouraging outcomes. Other advances have contributed to the FDA approval of three new medications in 2017 and 2019 for management of sickle cell disease, with several other drugs currently under development. In this review, we will focus on the most important advances in the last decade.

Integrating Datasets on Public Health and Clinical Aspects of Sickle Cell Disease for Effective Community-Based Research and Practice

“…We note that “community-based” is common to both the RuSH report and the NHLBI expert panel report. The advances in the past decade (2011 to 2020) on the therapy of sickle cell disease include: (1) modifying the patient’s genotype; (2) targeting hemoglobin S polymerization; (3) targeting vasocclusion; and (4) targeting inflammation [ 55 ]. These advances in genome science and technology have led to potential therapy for sickle cell disease using CRISPR genome editing technology.…”

Depression in adults with sickle cell disease: a systematic review of the methodological issues in assessing prevalence of depression

“…One interesting finding is that the prevalence appears to have decreased globally over the last 20 years when considering studies using only psychometric assessment (Table 4 ). This may be because the quality of life with the disease has improved or because of the progress in the global management of sickle cell disease and the introduction of new treatments in the last 20 years [ 55 , 56 ]. However, in the USA this decrease appears to plateau.…”

P-Selectin Blockade in the Treatment of Painful Vaso-Occlusive Crises in Sickle Cell Disease: A Spotlight on Crizanlizumab

“… 50 Allogeneic hematopoietic cell transplant and autologous stem cell-based gene therapy are attractive options for curing SCD in eligible patients. 51 Gene therapy has cured a few patients in small single-arm studies, but it has not generated any FDA approvals thus far. Voxelotor, a sickle cell hemoglobin polymerization inhibitor, was approved for SCD after it was shown to improve hemoglobin levels and reduce hemolysis, but it did not lead to a statistically significant reduction in the incidence of VOEs.…”