Advances in Sickle Cell Disease Treatments

Abstract

: Sickle Cell Disease (SCD) is an inherited disorder of red blood cells that is caused by a single mutation in the βglobin gene. The disease, which afflicts millions of patients worldwide mainly in low income countries, is characterized by high morbidity, mortality and low life expectancy. The new pharmacological and non-pharmacological strategies for SCD is urgent in order to promote treatments able to reduce patient’s suffering and improve their quality of life. Since the FDA approval of HU in 1998, there have been few advances in discovering new drugs; however, in the last three years voxelotor, crizanlizumab, and glutamine have been approved as new therapeutic alternatives. In addition, new promising compounds have been described to treat the main SCD symptoms. Herein, focusing on drug discovery, we discuss new strategies to treat SCD that have been carried out in the last ten years to discover new, safe, and effective treatments. Moreover, nonpharmacological approaches, including red blood cell exchange, gene therapy and hematopoietic stem cell transplantation will be presented.

Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials

“…The FDA approved voxelotor for SCD patients above 12 years of age. It is considered for patients who are refractory to hydroxyurea therapy or cannot tolerate hydroxyurea therapy or as an additional therapy in patients with worsening anemia [12].…”

Phthalimide as a versatile pharmacophore scaffold: Unlocking its diverse biological activities

“…Sickle cell disease (SCD) is a genetic disorder caused by a single-point mutation of β-globin, which produces sickle Hb (HbS) when valine is substituted for glutamic acid in the β-chain of hemoglobin (Kato et al, 2018;Pavan & dos Santos, 2021;Dos Santos & Chin, 2011).…”

“…Sickle cell disease (SCD) is a genetic disorder caused by a single‐point mutation of β‐globin, which produces sickle Hb (HbS) when valine is substituted for glutamic acid in the β‐chain of hemoglobin (Kato et al, 2018; Pavan & dos Santos, 2021; Dos Santos & Chin, 2011). The polymerization of HbS under deoxygenated conditions causes red blood cells to take on a sickle shape, resulting in cellular aggregates, vaso‐occlusion, and inflammation (Osunkwo et al 2021).…”

The Present Condition of Sickle Cell Disease: An Overview of Stem Cell Transplantation as a Cure

“…22 A humanized monoclonal antibody called crizanlizumab binds to P-selectin, which is expressed on the surface of platelets and endothelial cells. 23,24 These cells express P-selectin during activation processes like inflammation. 25,26 This starts the leukocytes' adhesion to the endothelium through the leukocytes' Pselectin glycoprotein ligand 1 (PSGL-1).…”