Abstract In vitro gene editing using isogenic pairs of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes has demonstrated the feasibility of introducing or correcting specific pathogenic variants. These successes represent a key first step toward therapeutic genome editing for cardiomyopathies, showing that precise, variant-specific interventions are achievable. To translate in vitro findings to the clinic, it is essential to develop robust disease models that yield meaningful, translatable data. However, in this systematic review, we reveal a lack of patient details, which creates an incomplete picture of underlying disease variables that hinder the design of targeted personalised treatments. Omitted key clinical data can lead to misinterpretations or overlooked variables that impact treatment outcomes. The next challenge is systematically identifying disease-causing variants amenable to gene editing with strong preclinical support. Therefore, we conducted a systematic search of published studies on isogenic hiPSC-CM pairs in cardiomyopathy research with specific criteria, including (likely) pathogenic variant causing cardiomyopathy, correction and/or introduction of variant, differentiation into cardiomyocytes, and functional follow-up. We systematically assessed 785 papers and highlighted 101 studies meeting our inclusion criteria reporting 69 patients carrying 56 unique variants across 32 genes, most commonly MYH7, MYBPC3, and DMD. However, reported clinical data were often incomplete, underscoring the need for standardised phenotypic documentation. This systematic review integrates current evidence from successful in vitro studies using isogenic hiPSC-CM models and proposes a reporting framework for variant prioritization and the rigorous application of isogenic controls in cardiomyopathy research.
Veltrop et al. (Tue,) studied this question.