Researchers used a gene therapy technique in a mouse model to greatly reduce the potential for ventricular tachycardia (VT), a lethal complication after a heart attack. VT, a heart rhythm disorder characterized by a faster than normal heart beat, occurs because the cells that replaced damaged heart cells are unable to conduct electrical signals like normal cardiomyocytes. The research team demonstrated that delivering Connexin 43 (Cx43), a gap-junction protein, into the heart lesion provided protection from arrhythmia in vivo. The study findings were published in Scientific Reports.
Using lentivirus-based gene transfer, the team transduced non-cardiomyocytes with the Cx43 gene. Overexpression of Cx43 in these non-excitable cells in the scar area of the heart resulted in an increase of electrical conduction velocity between native excitable heart cells and the damaged area of the heart. These results suggest that the gap junction protein facilitates electrical coupling between non-cardiomyocytes and native myocardial cells.
"We've created a bridge for the electrical signal," Bernd Fleischmann, M.D., professor and chairman of the Institute of Physiology at the University of Bonn and leader of the study. "We suspected it would work. We suspected that the cells we were putting in were actually working in this way, but it is really exciting."
The team plans to continue the study in larger animals knowing that their success with mice does not necessarily mean they will see the same outcome in humans. There is significant difference in size between mouse and human hearts and scaling up the treatment might not be successful. However, the researchers are enthusiastic about the ease and simplicity of the procedure and plan to continue their investigation.
"It could be a very simple medical procedure," said Michael Kotlikoff, professor of molecular physiology at Cornell University. "One could imagine a relatively noninvasive procedure in which the gene is introduced through a catheter, resulting in long term protection."