Cardiotoxicity is a growing issue in Oncology: cardio-oncology is an emerging discipline focused predominantly on the detection and management of cancer treatment-induced cardiac dysfunction (cardiotoxicity). Around 20% of all cancer survivors will develop cardiovascular co-morbidities, with 1 in 10 cancer patients dying from cardiovascular complication, rather than cancer. In 2016, the European Society of Cardiology (ESC) established a task force of KOLs, raising the urgent need to evaluate the impact of anticancer drugs on cardiotoxicity linked morbidity and mortality. This led to the 2016 ESC position paper developed under auspices of the ESC committee for Practice Guidelines in the European Heart Journal, Zamorano et al. (2016).
Metabolic modulation and cardioprotection
HFrEF occurs when the left ventricular ejection fraction (LVEF) is 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodelling. Worldwide, the burden of heart failure has increased to an estimated 23 million people, and approximately 50% of cases are HF-rEF. Despite several therapeutic options, heart failure with reduced ejection fraction remains a significant burden on economy and healthcare with persisting high mortality and hospitalisation rates. Thus unmet need for new therapies in the treatment of heart failure with reduced ejection fraction remains thus very high.
Loss of cardiomyocytes (heart cells) is the primary hallmark of heart failure. However, unlike other cell types, there is a limited capacity for cardiomyocytes proliferation in the adult heart and in the failing human heart. Therefore, regenerative approaches to replenish the lost cardiomyocytes are necessary to recover the contractile capacity of the heart and prevent death. Targeting cardiomyocyte proliferation is a potential new therapeutic strategy for myocardial regeneration and repair. Using our platform, we have uncovered novel therapeutic RNAi approaches that aid heart cell regeneration and proliferation. Patents, publications in progress; compounds validated in preclinical models.
Kearns-Sayre Syndrome (KSS) is a mitochondrial disease, with Rare Disease designation (7,400 – 22,000 patients in Europe), caused primarily by large-scale mitochondrial DNA deletions. Cardiac dysfunction is the principal clinical manifestation and primary cause of death. There are no current treatment options available that go beyond addressing some of the symptoms associated with KSS thus the unmet need is very high.