Geron Corporation (Nasdaq:GERN) today reported positive preclinical study data showing that GRNCM1, Geron's cardiomyocyte product derived from human embryonic stem cells (hESCs), does not cause cardiac arrhythmias after transplantation into a model of chronic heart damage designed to test this potential safety concern. GRNCM1 is being developed for the treatment of heart failure.
“Others have reported that certain cell types may cause arrhythmias when transplanted into the heart. Showing that GRNCM1 does not have this potential is an important step in demonstrating preclinical safety as we move towards our IND-enabling studies for this product.”
The data were presented today at the 31st Annual Scientific Sessions of the Heart Rhythm Society in Denver, CO by Geron collaborator Dr. Michael Laflamme from the University of Washington Medical School in Seattle, WA.
"We used a guinea pig model of chronic cardiac injury to screen for arrhythmias following the transplantation of human embryonic stem cell-derived cardiomyocytes," said Michael Laflamme, M.D., Ph.D. "Over the four week monitoring period post-transplantation, we found no significant difference in the incidence of premature ventricular contractions or ventricular tachycardia between recipients of the cardiomyocytes or vehicle controls. More safety testing is certainly warranted, but this is a reassuring first step with regard to the risk of arrhythmias."
"We are very pleased with these data on our hESC-derived cardiomyocytes," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "Others have reported that certain cell types may cause arrhythmias when transplanted into the heart. Showing that GRNCM1 does not have this potential is an important step in demonstrating preclinical safety as we move towards our IND-enabling studies for this product."
The current study assessed whether transplantation of GRNCM1 would increase the incidence of cardiac arrhythmia, which is a potential safety concern for cardiac cellular therapies. An arrhythmia is an abnormality of the heart rhythm, which can cause the heart to pump less efficiently.
Arrhythmogenic potential of GRNCM1 was assessed using a guinea pig model, because this animal's heart rate and electrophysiology are similar to humans. Myocardial infarction was induced by cryoinjury one month prior to injection of either GRNCM1, or non-cardiac hESC-derived cells or vehicle only as controls. Telemetric electrocardiogram (ECG) recordings were obtained at multiple timepoints during the study from the time of injury until one month after transplantation to compare the incidence of spontaneous arrhythmias across the study groups. Separately, programmed electrical stimulation was also used in this study to test the susceptibility of the treated animals to arrhythmias, especially ventricular tachycardia, intentionally induced by repeated electrical stimulation of the heart under anesthesia.
As expected, all injured hearts showed some spontaneous arrhythmias, particularly around the time of infarction and transplantation. Importantly, there was no significant difference in the incidence of either spontaneous or induced arrhythmias between the recipients of GRNCM1 and vehicle, demonstrating the lack of arrhythmogenic potential of GRNCM1 in this setting of myocardial infarction.
Geron is currently conducting studies of GRNCM1 in a swine model of myocardial infarction to further assess preclinical safety and efficacy of GRNCM1 in an additional animal model with a cardiovascular system of similar size and structure to humans.
Previously, Geron scientists and collaborators from the University of Washington Medical School showed that when GRNCM1 was transplanted into a rodent model of acute myocardial infarction, human cardiac grafts survived in the infarct zone. Analysis by echocardiography and MRI showed significantly improved cardiac structure and contractile function compared to controls. These data were published in the journal Nature Biotechnology.
According to the American Heart Association, congestive heart failure, a common consequence of heart muscle or valve damage, affects approximately 5.8 million people in the United States and approximately half of those diagnosed will die within five years. Each year over 1.2 million people have a heart attack, which is the primary cause of heart muscle damage. GRNCM1 could treat heart failure by replacing damaged myocardium with new viable cardiac cells to restore cardiac function.
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