(Press-News.org) Cardiac arrhythmias affect millions across the world and are responsible for a fifth of all deaths in the Netherlands. Currently there are multiple treatment options, ranging from life-long medication to invasive surgical procedures. Research from Amsterdam UMC and Johns Hopkins University, published today in the European Heart Journal, sets another important step in the hunt for a one-off gene therapy that could improve heart function and protect against 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.
The research team aimed to resolve conduction slowing for the first time through the insertion of a novel gene into heart muscle cells.
"The search for a gene therapy is not a new one but until now we had the pretty fundamental problem that the potential 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.
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.
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.
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.
END
A new gene identified in the search for a therapy to treat malignant cardiac arrythmia
2025-02-20
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