Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy.

ABSTRACT: Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca²⁺ handling is a key feature of HF pathophysiology. Restoring the Ca²⁺ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and lead

SUBMITTER: Grote Beverborg N 

PROVIDER: S-EPMC8405807 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature