Influence of the pyruvate kinase activator mitapivat (AG-348) on RBC ATP content and export and RBC adhesivity in blood from healthy subjects and sickle cell disease patients - Summary - MDSpire
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Influence of the pyruvate kinase activator mitapivat (AG-348) on RBC ATP content and export and RBC adhesivity in blood from healthy subjects and sickle cell disease patients
To investigate the effects of the pyruvate kinase activator mitapivat (AG-348) on ATP export from red blood cells (RBCs) in healthy individuals and patients with sickle cell disease (SCD).
Approach:
Study Design: Whole blood from SCD patients and healthy adults was incubated with AG-348 or vehicle, followed by RBC isolation and exposure to normoxic or hypoxic conditions. ATP levels were measured, and adhesion assays were performed.
Key Findings:
PKRA treatment increased intra-RBC ATP in healthy controls but did not significantly affect SCD RBCs.
ATP export from healthy RBCs increased after hypoxia and PKRA treatment.
SCD RBCs showed increased ATP export in hypoxia, but PKRA treatment did not significantly enhance this effect.
SS RBC adhesion to laminin decreased after exposure to AG-348 at relevant shear stresses.
Interpretation:
The study indicates that PKRA enhances ATP levels in healthy RBCs, but does not have the same effect in SCD RBCs under the tested conditions.
Limitations:
The study was limited to ex vivo conditions and may not fully represent in vivo responses.
The sample size and demographic details of SCD patients were not specified.
Conclusion:
ATP export mechanisms differ between healthy and SCD RBCs.
