After over 10 years of research, scientists in the United States have demonstrated—for the first time—the feasibility of a somatic cell reprogramming strategy for creating a biological pacemaker in a large animal preclinical model. Eugenio Cingolani, assistant professor of Medicine and director of Cardiogenetics-Familial Arrhythmia Clinic, Cedars-Sinai Heart Institute, Los Angeles, USA, co-author of the study recently published in Science Translational Medicine, speaks to Cardiac Rhythm News about their findings.
What is the rationale for the development of a biological pacemaker?
More than 300,000 pacemakers are implanted each year in the United States. While effective, complications from hardware malfunction or infection can occur. A biological pacemaker generates spontaneous heart beats with the injection of a single gene, relieving the need of an electronic device.
Could you explain how a biological pacemaker works?
With the injection of a single gene (TBX18), normal heart cells are transformed or reprogrammed to pacemaker cells that provide a stable rhythm to support the haemodynamic needs.
Tell us about your initial findings
We delivered a single gene (TBX18) via a minimally-invasive technique (catheter-based) in a preclinical model of heart block. After TBX18 injection, a physiologically relevant heart rate was seen during the two-week follow-up period. In contrast, control animals had a slow rhythm were dependent on the electronic backup device. Additionally, TBX18 animals exhibited enhanced response to physical activity and higher levels of activity compared to controls. No signs of local or systemic toxicity were seen.
What are the limitations of the current study?
We are currently doing long-term studies to prove efficacy and safety in a long-term period. [The follow-up period in the current study was 14 days].
Are there any other studies on the subject published in the literature?
Yes, our group [Cedars-Sinai Heart Institute, Los Angeles, USA] and others have been working on biological pacemakers for over a decade. This is the first pre-clinical study able to create a biological pacemaker by a clinically-feasible, minimally-invasive delivery technique, with somatic reprogramming by a single gene (TBX18).
What kind of patients could potentially benefit the most with the biological pacemaker?
Initially, we plan to use the biological pacemaker in high-risk patients such as those afflicted with device-related infections that require complete hardware removal and treatment with antibiotics. Other highly important population is congenital heart block, frequently associated with hydrops fetalis and stillbirth. Intra-uterine delivery of a biological pacemaker could represent a lifesaving therapy for this condition where electronic devices cannot be implanted. If proven effective in these two high-risk populations, we could then expand the indication to other populations.
How far are we to start human testing?
After completing long-term efficacy and safety studies, we plan to start human trials within three years.
Could biological pacemakers potentially replace current pacemakers— including leadless pacemakers—in the future?
Yes, if proven effective in human trials, a biological pacemaker could replace electronic devices including leadless pacemakers. A biological, hardware free alternative, can potentially restore your normal heart function, giving you a stable rhythm capable to adjust to your haemodynamic needs without the need of artificial hardware.