PLN-L31A/I40A for the treatment of inherited heart disease caused by PLN-R14del mutations

Deletion of the 14th arginine of phospholamban (PLN) is associated with severe cardiac dysfunction and premature death in a mouse model.

• PLN-R14del mice exhibited severe ventricular dilation and cardiac fibrosis.
• PLN aggregation was observed in both the PLN-R14del mouse model and human cardiomyocytes derived from gene-edited stem cells.
• Reduced cardiomyocyte function was noted in human PLN cardiomyocytes differentiated from gene-edited hESCs.
• Gene therapy using PLN-L31A/I40A demonstrated a therapeutic effect by blocking the interaction between PLN-R14del and the calcium transporter SERCA2α.
• The findings suggest potential for alternative treatment modalities to disrupt the PLN-R14del and SERCA2α interaction.

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