Scimitar Equity Blog

Positive preclinical study data showed that GRNCM1, GERN’s cardiomyocyte product derived from human embryonic stem cells (hESCs), does not cause cardiac (heart failure) arrhythmias after transplantation into a model of chronic heart damage designed to test this potential safety concern.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. GRNCM1 is being developed for the. GERN 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.

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.

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 cryo-injury 1 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 time points during the study from the time of injury until 1 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.

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. The data was presented 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. This data was published in the journal Nature Biotechnology.