Gene therapy improves electrical conduction after heart attack

After a severe heart attack, many heart muscle cells die and are replaced by scar tissue to stabilize the heart wall. Fibroblasts dominate in the scarred region, but these cells are not contractile and transmit electrical impulses poorly. "Unfortunately this cells are not contractile and also delay the conduction of electrical impulses in the lesioned area,” says Prof. Wilhelm Röll, senior physician at the UKB Heart Center and member of the Transdisciplinary Research Area (TRA) "Life & Health" at the University of Bonn. Prof. Bernd K. Fleischmann, co-corresponding author, adds: "Fibroblasts only express small amounts of the gap junction protein connexin 43, which is essential for the conduction of stimuli between heart muscle cells." 

The team used the Moloney Murine Leukemia Virus (MMLV) as a viral vector, combined with magnetic nanoparticles (MNP). This “gene shuttle” was introduced into cardiac fibroblasts using a magnetic field, enabling the cells to produce connexin 43. “The novelty of the approach was the use of the retrovirus MMLV, which introduces genetic information into fibroblasts in the heart in a relatively specific manner, but not into heart muscle cells, a process known as transduction,” explains co-first author Timo Mohr, a doctoral student at the University of Bonn. The therapy was further combined with the fluorescent reporter mCherry to verify successful transduction. 

Three days after inducing a heart attack in mice, researchers injected the MMLV/MNP complexes directly into the lesion area. Two weeks later, fibroblasts in the scar tissue were found to express connexin 43. Functional tests showed that treated mice experienced dangerous cardiac arrhythmias only about half as often as untreated controls. “With this concept, we were able to achieve substantial transduction of myofibroblasts in a relatively short time,” says co-first author Dr. Miriam Schiffer. 

According to Prof. Röll, “In principle, this therapy could be used in clinical applications at a later stage, possibly also for indications outside the cardiovascular system. However, suitable vectors to transduce human cardiac fibroblasts must first be identified and the clinical results confirmed in a large animal model.” 

MEDICA-tradefair.com; Source: University Hospital of Bonn (UKB)