Researchers have identified a gene therapy that could prevent life-threatening arrhythmias by restoring the heart’s electrical rhythm.
The key breakthrough? Finding a gene small enough to fit inside a viral delivery system. Early results in lab models suggest this therapy could be a game-changer, but further research is needed before it reaches clinical trials.
The Urgent Need for Better Arrhythmia Treatments
Cardiac arrhythmias affect millions worldwide and contribute to one in five deaths in the Netherlands. Current treatment options range from lifelong medication to invasive surgeries. However, new research from Amsterdam UMC and Johns Hopkins University, published today (February 20) in the European Heart Journal, marks a significant step toward a potential one-time gene therapy that could enhance heart function and prevent arrhythmias.
“Arrhythmias often occur due to slowing of conduction of the electrical impulse through the heart. Rapid impulse conduction is needed for the heart to beat in a steady rhythm. When this is disturbed, the patient may experience a life-threatening cardiac arrhythmia. Among others, conduction slowing and arrhythmias can occur in patients who suffer from a heart attack, heart failure, or from a genetic cause,” says Gerard Boink, cardiologist at Amsterdam UMC and coordinating author of the study.
For the first time, the research team aimed to correct this conduction slowing by introducing a novel gene directly into heart muscle cells.
A Major Challenge in Gene Therapy
“The search for a gene therapy is not a new one but until now we had the pretty fundamental problem that the potentially effective genes we had identified were too large to be transported via a viral vector into heart muscle cells,” says Boink. “Think of this vector like being a suitcase, up until now most of the relevant genes were just too big to fit in,” he adds.
Researchers from the department of Medical Biology at Amsterdam UMC have recently discovered a gene (SCN10a-short, S10s), which is small enough to fit into an AAV vector, the most efficient gene delivery platform for the heart.
“Finding a small enough gene was of course a crucial first step and in S10s we also have found a gene that may be able to reverse the conduction slowing and allow the heart to beat at its regular rhythm,” says Phil Barnett, who works as a senior researcher in the Department of Medical Biology.
Early Success in Animal and Human Models
The research team has shown for the first time in the current study that it is possible to introduce S10s into the heart with an AAV vector and that this leads to faster conduction and, thus, a potential therapeutic for the prevention of cardiac arrhythmias. This has been demonstrated in various animal models, but also in human heart muscle cells derived from stem cells and a computational model of the human heart.
“These are great early steps but now we need to continue our research in order to find out if this approach will really translate into clinical practice. If it does, then we should be able to significantly reduce the occurrence of arrythmias and make a meaningful impact on patient mortality,” says Boink.
Bridging Research and Real-World Application
To facilitate this, Boink has, together with fellow Amsterdam UMC cardiologist Hanno Tan and anaesthesiologist Otto Kirzner, launched a spin-off company called Pacing Cure. The company aims to “serve as a stepping stone” to facilitate quicker clinical progress.
Reference: “SCN10A-short gene therapy to restore conduction and protect against malignant cardiac arrhythmias” 20 February 2025, European Heart Journal.
These follow-up studies are being carried out in collaboration with the Amsterdam UMC, Departments of Medical Biology, Experimental Cardiology, Clinical Cardiology and the spin-off company PacingCure B.V., and will be financed by the European Innovation Council and the Dutch Heart Foundation.
