Heart Failure with Preserved Ejection Fraction

In partnership with AstraZeneca, Novoheart has created the first in vitro human HFpEF mini-Heart.

Patients with Heart Failure with Preserved Ejection Fraction (HFpEF) have grown in number and currently comprise ~50% of the overall heart failure population. HFpEF patients have debilitating symptoms such as fatigue, weakness, shortness of breath with minimal exertion or at rest, and they experience high incidence of morbidity and mortality. There are very few effective treatments for HFpEF and no disease modifying therapies. Therapies that reduce mortality and morbidity in Heart Failure with reduced Ejection Fraction (HFrEF) have little effect in HFpEF, as the etiology and the clinical course are different. Animal models fail to adequately mimic this human pathophysiology.

https://www.medera.bio/mederas-novoheart-partners-with-astrazeneca-on-first-bioengineered-human-models-of-heart-failure-with-preserved-ejection-fraction/

Friedreich’s ataxia

In partnership with Pfizer, Novoheart has created the first human FRDA mini-Heart^TM assays, which recapitulate key electrical and mechanical defects of the heart observed in FRDA patients to provide a comprehensive in vitro platform for screening novel cardiotherapeutics.

Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by a non-coding mutation in the frataxin (FXN) gene that suppresses the expression of this protein. Dilated cardiomyopathy, hypertrophic cardiomyopathy, and conduction system abnormalities that result from the disease lead to fibrosis and cardiomyocyte death, consequently resulting in heart failure and arrhythmias. Differences between murine and human genetics and metabolism have limited the clinical relevance of prior animal studies of FRDA.

Wong et al. (2019) Stem Cell Research and Therapy 10(1):203

Drug-induced Long QT Syndrome and Arrhythmias

Disturbances in cardiac electrical conduction are a major cause of cardiotoxicity.  However, life-threatening electrophysiological phenomena such as arrhythmias (heart rhythm disorders) are multi-cellular phenomena that cannot be always accurately predicted using typical single cell measurements such as action potential prolongation.  For example, isolated single cardiomyocytes of Long QT patients might display single-cell electrical defects but the patients mostly live a normal life until episodes happen. Therefore, a versatile sensitive system is needed to clearly detect the susceptibility for arrhythmias under what conditions. The hvCAS assay uses a precisely aligned monolayer of hvCMs enabled by our patented microgrooved substrate technology to reproduce the specific electrical anisotropy observed in native heart muscle. 

For the first time, we have successfully used the hvCAS system to visualize the life-threatening adverse electrical effects of several drugs failed in the Cardiac Arrhythmia Suppression Trial (C.A.S.T.) by causing lethal effects in patients although they otherwise passed the traditional preclinical screening process.  We have also modeled complex non-monogenic conditions such as drug-induced long QT.

Shum et al. (2017) Advanced Material 29:  1602448

Stillitano et al. (2017) eLife 6: E19406

COVID-19

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the heart and circulatory system in many ways. For example, it can lead to a faster heart rate, atrial fibrillation, blood clots, heart damage due to a lack of oxygen and nutrients, inflammation of the heart muscle and lining or myocarditis. Novoheart has used our proprietary mini-Heart technology to study the functional consequences of COVID-19 vaccines, medications and spike proteins, etc.

Yuan et al. (2021) Nature 593(7859):418-423

Wong et al. (2021) Journal of Molecular and Cellular Cardiology 153:106-110