Phospholamban (PLN) cardiomyopathy is a heart disease caused by a rare genetic mutation (R14del), which is thought to have originated in the Netherlands several centuries ago. Mutation carriers are at great risk of developing cardiomyopathy with heart failure but, remarkably, not everyone with this mutation also develops symptoms – a significant number of mutation carriers never notices anything is wrong. Since there is no accurate model to investigate this disease, it is unknown why some carriers are affected more than others, and a successful cure is nonexistent.
Therefore, Tim Eijgenraam and his team have generated a novel mouse model of PLN cardiomyopathy, and have tested the efficacy of standard heart failure therapy on the disease presentation. Preliminary results have previously been presented at several European congresses for cardiovascular research, which resulted in two runner-up prizes during Young Investigator Award sessions in 2018 and 2020. Since then, their work has progressed, and has now been published in Nature’s journal Scientific Reports.
In their study, Eijgenraam and his colleagues show that mice with the R14del mutation develop heart failure with similar characteristics as human mutation carriers. Interestingly, abnormal localization of the PLN protein was detected in the heart cells. This observation has previously been described in human hearts but has not been extensively researched, and could be a key target for novel therapies. Standard heart failure medicine had no beneficial effects, emphasizing the need for a better suitable treatment for patients with this mutation. This translational model offers a great opportunity to further research the disease mechanism, and to investigate risk factors and possible treatment options.