4.6 Article

A Proposed Concept for Defective Mitophagy Leading to Late Stage Ineffective Erythropoiesis in Pyruvate Kinase Deficiency

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AG-348 (mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and adenosine triphosphate levels over a broad range of PKLR genotypes

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Summary: The study found that ex vivo treatment with AG-348 increased enzymatic activity and ATP levels in PK-deficient patient cells, leading to improved RBC deformability. AG-348 may effectively up-regulate PK enzymatic activity and stabilize PK-deficient RBC, potentially correcting the underlying pathologies of PK deficiency.

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