Nanomedicine gene therapy to treat Phospholamban cardiomyopathy
In Nanoparticle-based PhosphoLambaN CArdiac REpair (Nano-PLNCARE), University Medical Center Utrecht and PLaN Therapeutics will develop a state-of-the-art full-scale gene therapy platform in which cardiac delivery is enhanced to develop a treatment for PLN cardiomyopathy.
Chronic heart failure, associated with genetic and ischemic cardiomyopathy, and its complications, including disability and soaring costs, affect 0.5-2.2% of the population in industrialized countries, consuming 1–2% of the total healthcare resources. Existing medical symptom management focusses on improving cardiac function by medication. The mutated variant of phospholamban (PLNR14del) can cause a severe cardiomyopathy in carriers of this mutation with life-threatening arrhythmias, sudden cardiac death, and dilated cardiomyopathy. Phospholamban (PLN) encodes for a transmembrane sarcoplasmic reticulum (SR) phosphoprotein and is crucial in the regulation of calcium cycling in cardiomyocytes. In the Netherlands alone, PLN-R14del is responsible for approximately 10% to 15% of patients with dilated cardiomyopathy (DCM) and 15% with arrhythmogenic cardiomyopathy (ACM). Gene therapy is seen as a curative approach for a variety of acute and chronic diseases, not limited to heart failure, having almost unlimited treatment possibilities.
In this project, we are creating an innovative isolated perfusion platform and delivery technology that allows for isolated organ treatment, without systemic side-effects. In clinical relevant models, we will specifically restore the PLNR14del malfunction leading to improved cardiac performance. This will create opportunities for not only PLNR14del cardiomyopathies, but also for several (genetic-caused) cardiomyopathies in which genetic modification or repair is curative. We anticipate that successful application of the novel therapeutic approach described will translate to human patients, significantly reducing a multi-billion-dollar unmet health care burden and improving the quality of life for many millions of patients worldwide and in the Netherlands.
