You sometimes read about them in the news and they are events that leave you dismayed. Because they often concern very young people budding athletes or even professional sportsmenwho suddenly collapse on a football pitch, during a run or in the middle of a volleyball match: if medical aid does not intervene promptly, there is nothing that can be done. Sudden cardiac death affects a thousand people under 35 every year and this is often the first (and unfortunately last) manifestation of an occult heart disease; in some cases it is the arrhythmogenic cardiomyopathya disease for which today there is new hope thanks to a gene therapy developed at the IRCCS Maugeri by Silvia Priori, professor of Cardiology at the University of Pavia.
Arrhythmias in the very young
Arrhythmogenic cardiomyopathy is a rare genetic diseasewhich concerns approx 5 thousand people in the worldin which the heart has a lower ability to contract and arrhythmias appear: it often manifests itself in adolescence, with a greater prevalence in those who practice intense sporting activity, but diagnosing it early is difficult because the symptoms are not very specific. Today it can be controlled with beta-blocking drugs, but the treatment requires high adherence which worsens the quality of life in very young people; for some then the implant is needed a defibrillatormoreover in fact it is recommended not to practice sports with a high impact on the heart, given the risk of palpitations, fainting and sudden cardiac death with intense exertion. «Arrhythmogenic cardiomyopathy is caused by the mutation of the gene that produces the proteins responsible for holding together the cells that make up the heart tissue – explains Priori -. The alteration of the gene reduces the quantity and structure of these proteins, resulting in detachment of the myocardial cells which, when separated, leave empty spaces in which fibrous tissue forms which makes the heart muscle less elastic and incapable of contracting and pumping blood. If the pathology is not treated promptly, it tends to worsen until it transforms into heart failure. This already critical picture is associated with the fact that the presence of fibrous tissue acts as an obstacle to the propagation of the heart’s electrical impulses, giving rise to serious arrhythmias.”
Gene therapy
The gene therapy studied by Priori, who follows around a hundred of these patients at the IRCCS Maugeri, could resolve the disease at its root because it delivers synthetic DNA to the heart that contains the instructions for producing the missing protein. «Once synthesized, the “normal” gene is inserted into a virus which is totally harmless and therefore acts as a vector, a “biological syringe” which enters the patient’s cells, reaches the nucleus and injects the DNA produced in the laboratory, initiating thus the synthesis of the missing protein – says the expert -. Adeno-associated viruses are generally used (viruses with a single DNA strand that have been isolated together with adenoviruses and are defective, i.e. they need other viruses to be able to cause an infection, ed), which also have the characteristic of entering only some cells of the organism. For example, adeno-associated type 8 and type 9, once injected into the bloodstream, selectively go to the heart.”
Just one administration is enough
The result is an increase in the production of the missing protein which in experimental animals has given very positive results, demonstrating that some arrhythmias can actually be resolved. The objective is to start clinical studies soon: for example, candidate patients are being characterized to understand who might respond to the treatment and who not, evaluating among other things the presence of antibodies for adeno-associated viruses, which may have already been “encountered” making the viral vector ineffective, because it would be immediately recognized and eliminated by the immune system. If the efficacy is confirmed in humans too, gene therapy will be a big step forward because, as Priori observes, «in theory, a single administration of gene therapy could be enough to solve the problem for several years». The data on animals allow us to estimate that the treatment with synthetic DNA can compensate for the effects of the genetic defect for at least ten years: if this is the case also in patients it will mean correct the arrhythmia, free yourself from long-term daily therapy with drugs and thus recover a better quality of life.
