Gene therapy for neonatal sarcomeric cardiomyopathies: towards first-in-patient

Funded period

2016 – 2019

Granted budget

€ 446,893



Therapeutic Principle

Gene therapy

Principal Investigator

Lucie Carrier (University Hospital Hamburg-Eppendorf)

One of the most frequent causes of cardiomyopathy in newborns are homozygous or complex heterozygous mutations of the MYBPC3 gene which encodes the cardiac myosin-binding protein C, a protein belonging to the sarcomere.

These congenital cardiomyopathies may rapidly turn into systolic heart failure and in serious cases result in death within the first year of life. Recently, we demonstrated a long-term prevention of the disease using MYBPC3 gene therapy in a homozygous Mybpc3-targeted knock-in mice, which genetically mimic human neonatal cardiomyopathies. In the absence of any treatment options except heart transplantation, gene therapy is a realistic treatment option for this subset of infants with severe and fatal neonatal cardiomyopathy. Our goal is to establish MYBPC3 gene therapy in a large animal model (pig) and thus move another important step closer to clinical application. Such a porcine model, which carries bi-allelic truncating MYBPC3 mutations and displays the cardiac phenotype of the cardiomyopathy in newborns, is not yet available. It will be generated using CRISPR/Cas9-technology, somatic cell nuclear transfer and embryo transfer. Once the porcine model has been successfully developed, the AAV9-mediated, cardiac-specific MYBPC3 gene transfer will be applied. If it turns out to be as successful as in mice, this therapy may perhaps be applied to the little patients in the foreseeable future


The mutation of the MYBPC3 gene using somatic cell nuclear transfer and embryo transfer impaired the viability of nuclear transfer fetuses and also of newborn piglets massive. Instead, the scientists introduced the mutation organ-specifically using the CRISPR/Cas-9 technique in transgenic pigs. In parallel, MYBPC3-gene therapy has shown encouraging results with heart muscle cells derived from pluripotent stem cells of humans with cardiomyopathy. In both Europe and the USA, a patent for 'Gene-therapy vectors for treating cardiomyopathy' has been issued. The DiNAQOR company was founded, which develops MYBPC3 gene therapy for patients with severe forms of cardiomyopathy. Professor Carrier and her colleagues are involved in preclinical studies testing MYBPC3 constructs in human induced pluripotent stem cell-derived cardiomyocytes and engineered heart tissues. (DZHK annual report 2019)