Mitapivat in hemolytic anemia: where do we stand now?

Introduction: Mitapivat (AG-۳۴۸) is a pyruvate kinase allosteric activator that was granted approval by the USFDA on February ۱۷, ۲۰۲۲, and by the European Union in November ۲۰۲۲ for treating hemolytic anemia inadult patients who suffer from pyruvate kinase (PK) deficiency. Mitapivat function is through allosteric bindingto the PK tetramer and enhances its activity, impeding adenosine triphosphate (ATP) depletion, erythrocytes'lifespan shortening, and chronic hemolysis. Subsequent investigations revealed that this drug possesses thepotential for application in other inherited conditions accompanied by hemolytic anemia, including sickle celldisease (SCD) and thalassemia.Methods: This study was performed by using the collected articles in English that were available on details ofthe main topic in Scopus, PubMed, and Web of Science with keywords mitapivat, pyruvate kinase deficiency,thalassemia, sickle cell disease, and hemolytic anemia, all in title/abstract field.Results: Administration of mitapivat results in heightened hemoglobin (Hb) levels, augmented erythrocytepyruvate kinase (PKR) functioning, and diminished levels of ۲,۳-diphosphoglycerate (۲,۳-DPG) in sickled redblood cells (RBCs), thus reducing Hb polymerization by bolstering Hb's affinity for oxygen, ultimatelyculminating in clinical manifestations alleviation. Some clinical evidence demonstrated the mitigation ofineffective erythropoiesis, iron overload, and anemia in a mouse model of β-thalassemia intermedia through theadministration of mitapivat followed by an investigation conducted on patients with α- or β-thalassemia who donot require blood transfusions, wherein the activation of PKR exhibited improvement in anemia.Conclusion: Hence, these effective outcomes offer a justification for the ongoing investigation of mitapivat asa potential therapy for disorders beyond pyruvate kinase deficiency, including thalassemia and SCD, even otheracquired conditions distinguished by dyserythropoietic and hemolytic anemia besides the exploration ofalternative PK activators

کلیدواژه ها:

Mitapivat ، Pyruvate kinase deficiency ، Thalassemia ، Sickle cell disease ، Hemolytic anemia