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Speaker: Dr Thomas Kampourakis, British Heart Foundation Research.
Host: Elisabeth Ehler
There remains a large unmet demand for new therapies in the treatment of both systolic and diastolic heart failure. However, recent advances in clinical and biomedical research have linked mutations in the major proteins of the sarcomere to heritable cardiomyopathies, including hypertrophic (HCM) and dilated cardiomyopathy (DCM), directly linking sarcomere function to heart muscle performance. Therefore, with the aim of achieving better drug efficacy and specificity, attention has been focused on directly targeting the major contractile proteins of the heart muscle sarcomere. However, the development of sarcomere-directed heart failure drugs has been largely impeded by incomplete understanding of normal filament function in situ and by the lack of in vitro screening assays that accurately reproduce that function. We exploited our recent advances in understanding the regulatory structural transitions in the myofilaments of heart muscle cells and developed new high-throughput screening platforms that allowed us to identify new potential sarcomere-directed small molecule effectors. We validated and characterized compounds identified in the primary screens using a wide range of physiological and biophysical techniques, and we are currently investigating the structure-activity relationship of potential lead compounds. Supported by the British Heart Foundation.
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