Research from Amsterdam UMC (Amsterdam, The Netherlands) and Johns Hopkins University (Baltimore, USA), published recently in the European Heart Journal, could represent an important step in the hunt for a ‘one-off’ gene therapy that can improve heart function and protect against arrhythmias.
“Arrhythmias often occur due to slowing of conduction of the electrical impulse through the heart,” said Gerard Boink (Amsterdam UMC, Amsterdam, The Netherlands), coordinating author of the study. “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.”
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,” Boink added. “Think of this vector like being a suitcase—up until now, most of the relevant genes were just too big to fit in.”
Researchers from the medical biology department at Amsterdam UMC recently discovered the SCN10a-short, S10s gene, which is small enough to fit into an adeno-associated virus (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,” stated Phil Barnett (Amsterdam UMC, Amsterdam, The Netherlands).
In the current study, the research team has shown for the first time 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,” Boink noted. “If it does, then we should be able to significantly reduce the occurrence of arrythmias and make a meaningful impact on patient mortality.”
To facilitate this, Boink has—together with Amsterdam UMC’s Hanno Tan and Otto Kirzner—launched a spin-off company called Pacing Cure. The company aims to “serve as a stepping stone” to facilitate quicker clinical progress.
