Antisense Oligonucleotide Therapy for Calmodulinopathy.

ABSTRACT:

Background

Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in CALM1, CALM2, or CALM3, which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function.

Methods

We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of CALM1 pathogenic variants.

Results

Human CALM1^F142L/+ induced pluripotent stem cell-derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 k

SUBMITTER: Bortolin RH 

PROVIDER: S-EPMC11747850 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature