As the leader of the only investigator-led HF network across Asia (ASIAN-HF), Singapore is uniquely placed in this proposal to employ a “reverse translational” approach from human to animal models. Genetic, epigenetic, clinical and imaging data from ASIAN-HF patients will be used to guide “reverse translation” to rodents. This will provide novel small animal models suitable for parallel advanced imaging in SBIC and immediately applicable to pre-clinical pharmaceutical studies.
We will further develop, in parallel, a large animal model of HFpEF which is urgently needed worldwide – there is, to date, no universally accepted or validated large animal model in HFpEF, and a great industry demand for such a model. Animal models allow longitudinal assessments of disease progression across stages in HF (complementary to the cross-sectional approaches in humans, since longitudinal progression in humans would take decades to study). Target validation in animal models and eventual “feed back” to the patient cohorts in clinical trials are anticipated next steps.