Arrhythmogenic heart disease, a new hope for a cure from gene therapy

Arrhythmogenic heart disease is a rare genetic disease characterized by a reduction in the ability of the heart muscle to contractassociated with frequent and intense arrhythmias. It affects one in 5 thousand people in the world and often manifests itself during adolescence, with a prevalence in subjects who practice intense sporting activity. It is a subtle pathology because it is characterized by non-specific symptoms, i.e. also common to other diseases, and this often makes early diagnosis difficult. Given the genetic nature of the disease, it cannot be prevented or definitively resolvedbut there are therapies that can control the symptoms as long as there is high therapeutic adherence, difficult to guarantee in very young subjects. For these patients, a new possibility of treatment opens up thanks to an innovative genetic therapy, which could improve their quality of life.

Reference center

The IRCCS Maugeri of Pavia is among the Italian excellences in the treatment of arrhythmogenic cardiomyopathy: the molecular cardiology unit, led by Silvia Priori, full professor of Cardiology and director of the School of Specialization in Cardiology at the University of Pavia, is a national and international reference center for the management of patients affected by genetically based arrhythmogenic pathologies. On the occasion of an event organized in the Pavia facility and open to patients and caregivers, Priori illustrated the benefits of gene therapyfor which clinical trials will soon begin.

Heart failure

«The cause of this disease is to be found in a mutation of the gene that produces the proteins responsible for holding together the cells that make up the myocardial tissue – explained Priori -. The alteration of the gene determines a reduction in the quantity and structure of these proteins, with consequent detachment of the myocardial cells: these, by separating, leave empty spaces in which fibrous tissue forms which makes the cardiac muscle less elastic and incapable of contracting and pump the blood. If the disease is not treated promptly, it tends to worsen and turn into heart failure. Furthermore, the presence of fibrous tissue acts as an obstacle to the propagation of the heart’s electrical impulses, giving rise to serious arrhythmias».

Unexpected death

The pathology manifests itself with palpitations, sudden faintingnot caused by other contributing causes (often during intense physical activity or in conjunction with strong emotions) and increased risk of sudden death. The diagnosis generally occurs on the recommendation of the sports doctor, through family screening or, at an early stage, on the basis of genetic testing. Patients suffering from this pathology are treated with beta-blocking drugssometimes also combined with the implantation of a transvenous defibrillator which reduces arrhythmias. But the first “therapy” to be implemented is total abstention from any sporting activity with a high impact on the heart.
In this context Gene therapy represents an important innovation: it does not limit itself to treating the symptom, but acts on the substrate that causes the diseasewith great hopes of being able to slow down its progress or even cure it.

DNA synthesized in the laboratory

«Arrhythmogenic cardiomyopathy is caused by a genetic defect, therefore the DNA is altered and produces an insufficient quantity of desmosomal proteins – explains Priori -. Gene therapy uses DNA synthesized in the laboratory, carried inside the heart cells by a harmless virus that is unable to replicate and which carries the therapeutic DNA into the nucleus of the heart cells, increasing the level of the deficient protein.” The great advantage of gene therapy, which treats the pathology by acting directly on its genetic bases through biological medicines, is that a single administration is sufficientwhile current therapies involve taking various drugs every day.

April 18, 2024 (modified April 18, 2024 | 7:10 pm)

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