Friedreich’s ataxia (FRDA) is an autosomal recessive disease that affects mainly the peripheral and central nervous systems, and heart. FRDA is caused by a GAA repeat expansion in the first intron of the frataxin (FXN) gene, leading to a reduced expression of FXN mRNA and frataxin protein. FXN, a mitochondrial protein involved in the biosynthesis of iron-sulfur proteins, is essential for oxidative metabolism. Hence, due to its high energy consumption, the heart is one of the first organs presenting pathological symptoms of FRDA. Indeed, cardiac dysfunction is the leading cause of death in FRDA patients. Although transgenic mouse models of FRDA have been previously created, the genotype, severity and disease phenotypes of human patients are not always reproduced.
In this free webinar, the featured speaker will discuss the use of human pluripotent stem cells (hPSCs) and tissue-engineered models to study FRDA cardiomyopathy. Human ventricular cardiac anisotropic sheets (hvCAS) and tissue strips (hvCTS) were generated from human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC)-derived ventricular cardiomyocytes (VCMs) for modelling FRDA’s electrophysiological and contractile defects, respectively.
The findings show that human-based FRDA in vitro models provide a biomimetic platform suitable to facilitate the study of the disease. The data suggest that tissue-engineered models fabricated using hPSC-derived ventricular cardiac cells cultured as anisotropic sheets and 3D tissue strips are key in understanding the pathogenesis of FRDA cardiomyopathy, and are suitable for pharmaceutical testing.
Tissue-engineered human in vitro models represent an important paradigm shift in the study of FRDA and other genetic cardiomyopathies including Barth syndrome, left ventricular noncompaction, hypoplastic left heart syndrome, familial hypertrophic cardiomyopathy and others. These human-relevant models hold the promise of revolutionizing the manner in which drugs are currently discovered and developed.
Bernard Fermini, Chief Research & Development Officer, Novoheart
Bernard Fermini received a PhD in Biophysics from the University of Sherbrooke (Canada) and completed post-doctoral training at Texas Tech University Health Sciences Center. He joined the Montreal Heart Institute where he led a team in the discovery of a novel human atrial selective potassium ion channel. Bernard then moved to Merck in West Point, PA, and worked on atrial antiarrhythmic agents before joining Pfizer in Connecticut, where he held positions of increasing responsibility, including associate director of global safety pharmacology and head of the Ion Channel Discipline. He is currently the Chief Research & Development Officer at Novoheart where he leads its industrial expansion into drug discovery and development. Bernard is a board member on the CiPA steering committee, a previous member of the board of directors of SPS and a current member of HESI’s cardiac safety committee and the Society of Toxicology.
Who Should Attend?
This webinar will appeal to safety pharmacologists and pharmaceutical/biotech/academic investigators working in the following or related areas:
- Cardiovascular therapeutic development
- In vitro testing
- Friedreich’s Ataxia
- Dilated cardiomyopathy
- Familial hypertrophic cardiomyopathy
- Barth syndrome
- Left ventricular noncompaction
- Hypoplastic left heart syndrome
- Arrhythmogenic right ventricular dysplasia
What You Will Learn
Participants will learn about:
- An overview of FRDA
- Opportunities and challenges of studying FRDA in animal models
- Review of study results involving hPSCs and tissue-engineered models
- Applications of tissue-engineered human in vitro models in the study of genetic cardiomyopathies
Novoheart is a global biotechnology company with offices and laboratories in Irvine, California, U.S., Vancouver, B.C., Canada and Hong Kong, China, listed on the Toronto and Frankfurt Stock Exchanges (TSXV:NVH, FRA:3NH). Pioneering an array of next-generation human heart tissue prototypes, it is the first company in the world to have engineered miniature living human heart pumps that can revolutionize drug discovery, helping to save time and money for developing new therapeutics. Also known as ‘human heart-in-a-jar’, Novoheart’s bio-artificial human heart constructs are created using state-of-the-art and proprietary stem cell and bioengineering approaches and are utilized by drug developers for accurate preclinical testing as to the effectiveness and safety of new drugs, maximizing the successes in drug discovery whilst minimizing costs and harm caused to patients. Novoheart has recently acquired Xellera Therapeutics Limited for US$26M to expand into the development of advanced therapeutics including cell- and gene-based therapies.
Leveraging technologies developed over two decades by an international team of eminent scientists and clinicians with broad expertise in stem cell, tissue engineering and regenerative medicine, Novoheart aspires to 1) revolutionize pre-clinical heart disease modelling and drug discovery; 2) advance pre-clinical and clinical development of novel therapeutics for cardiac regenerative medicine with a pipeline of candidates for clinical trials; and 3) establish the first commercial Good Manufacturing Practice (GMP) facility for advanced therapeutic production in Southern China for treatments of heart and other diseases to benefit the rapidly aging population.
The target market for Novoheart’s services and products include cardiovascular safety assessment groups within pharmaceutical and biotech companies. Additionally, cardiovascular diseasemodelling groups use our sophisticated cardiac models for better understanding of human disease, and to test therapeutic candidate treatments against complex cardiovascular disease asmodelled in our service offering.