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Genetic engineering to mend the heart

ESC Congress News 2018 - Munich, Germany

Today, Professor Silvia G. Priori (University of Pavia, Italy) will give the William Harvey Lecture on Basic Science (Sunday, 12:00 – 12:30; Brussels – Village 4).

Arrhythmias, General
Basic Science


priori-silvia-2018.jpgProf. Priori has been involved in the study of the genetic basis of inherited arrhythmogenic diseases and has contributed to the significant progress that has been made in this field. “In the past 20 years, we have seen the discovery of the first genes responsible for inherited arrhythmias, the establishment of genotype-phenotype correlations and now we are heading toward the development of genotype-based management strategies. However, current treatment with medication and implantable cardioverter-defibrillators is still not sufficient to reduce mortality and morbidity and patients still live with the anxiety that death could be around the corner.”

“The next frontier is developing gene therapies to fix the consequences of the molecular defects and to bring these therapies to the clinic.”

Gene therapy may represent an innovative therapeutic strategy to combat arrhythmogenesis. Prof. Priori and her team have contributed to the identification of novel genes associated with inherited arrhythmias, such as the discovery of mutations in the dominant gene that causes catecholaminergic polymorphic ventricular tachycardia (CPVT).1 Prof. Priori and her team have subsequently developed gene therapy strategies for both the dominant and the recessive forms of CPVT, adopting targeted strategies for each form of the disease.1

To provide a preliminary validation in humans of the gene therapy strategies, Prof. Priori’s group at the University of Pavia has validated the efficacy of their molecular strategies in human cardiac myocytes differentiated from induced pluripotent stem cells (iPSCs) of CPVT patients.2 These preclinical data were received with interest by the scientific community as they overcame the existing concern that gene therapy would not be effective in treating inherited arrhythmias and in fact could even be pro-arrhythmic by creating inhomogeneous protein expression among cardiac cells. Now that the spell of ineffectiveness of gene therapy to treat cardiac arrhythmias has been dismissed, at least in CPVT, the next challenge is to move toward a ‘first-in-man’ study and determine whether the novel therapies may provide a relevant clinical benefit.

Whether gene therapy strategies will be developed soon for other inherited arrhythmias is an intriguing question raised not only by scientists but also by affected patients and their families. Prof. Priori explains, “A key limitation to the development of molecular strategies for other genetically determined arrhythmias is represented by the lack of reliable preclinical animal models. More work is therefore needed to create models where the manifestations of diseases are similar to those of humans. These missing ‘advanced’ models may provide the leverage needed to establish a platform for further development of molecular therapies to treat lifethreatening inherited arrhythmias.”

1. Bongianino R, et al. Circ Res. 2017;121:525–536.

2. Lodola F, et al. Cell Death Dis. 2016;7:e2393.

 

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Notes to editor

About the European Society of Cardiology

The European Society of Cardiology brings together healthcare professionals from more than 150 countries, working to advance cardiovascular medicine and help people lead longer, healthier lives.

About ESC Congress 2018

ESC Congress is the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2018 takes place 25 to 29 August at the Messe München in Munich, Germany. Explore the scientific programme