Arrhythmogenic cardiomyopathy: a trial on a medicinal product able to inhibit the molecular mechanisms responsible for the risk of sudden cardiac death in young athletes and interrupt the progression of the disease has yielded promising preliminary results.
Scientific supervisor of the project:
Prof.ssa Alessandra Rampazzo
Molecular and Genomic Human Genetics Laboratory, Department of Biology
University of Padua
It happens suddenly: a young athlete drops to the ground during a match or practice session and dies, despite every attempt being made to resuscitate him or her. A tragic event that occurs all too often, and that affects both amateur enthusiasts and youngsters with a bright career ahead of them.
One of the most common causes is arrhythmogenic cardiomyopathy, a hereditary disease affecting 1 in every 5000 people that causes two deaths per 100 thousand subjects under 35 every year.
To date, there is no cure for this disease, with which the general public is unfortunately familiar for having struck well-known athletes and footballers. The treatment options currently available are merely palliative.
In individuals with specific genetic defects, exercise and the degenerative dynamics of the condition lead to the cells of the myocardium, especially the right ventricle, being replaced by fibrotic and adipose tissue. This process favours the development of heart arrhythmias, such as tachycardia and ventricular fibrillation, which cause cardiac arrest. Without prompt electrical defibrillation, ventricular defibrillation leads to sudden death within minutes.
Although a number of genes associated with the disease have been discovered (6 of which by our research group), the mechanisms that lead to the death of heart cells, their replacement by fibrotic and adipose tissue and, more generally, the evolution of the disease, are still largely unclear.
Our research group recently generated a transgenic mouse presenting the same adventitious characteristics observed in patients and that provides a good study model for identifying the causes of the disease.
More specifically, in conjunction with a research group from British Columbia University in Vancouver, we demonstrated that the cardiac adipose tissue derives from specific cells known as FAPs (fibro/adipogenic progenitors).
We may have reached a turning point in the trial of a medicinal product able to inhibit the differentiation of cardiac FAP cells into adipocytes.
Our recent studies have yielded encouraging preliminary results that, if confirmed, could lead to the identification of a specific drug in as little as 2-3 years.
Following the promising preliminary results of our studies, we recently obtained sponsorship from a pharmaceutical company in order to develop and implement our research.
If the preliminary data are confirmed, the study drug could become a promising candidate for a new pharmacological treatment that, for the first time, would block the molecular mechanisms of the disease, instead of treating its clinical signs, such as arrhythmias, using beta blockers and antiarrhythmic agents.
In order to develop this project, we need help: an annual full-time study grant to award to a medical biology/ biotechnology/ molecular biology graduate with three years’ experience in the molecular and cellular biology field and funding in order to conduct experiments on animal models. Every contribution we receive can help to significantly reduce research times, and save a great many lives.
The results obtained during the study will be disseminated through scientific publications and discussed at international congresses and in the national press. Sponsorship for research activities will be mentioned in all publications and presentations regarding the progress achieved.
Sponsorship required for animal model experiments: 180,000 euros
Sponsorship required for an annual study grant: 28,000 euros
Prof.ssa Alessandra Rampazzo