治療心肌病變之新藥開發

@ Introduction

Left ventricular noncompaction cardiomyopathy (LVNC) is a myocardial disorder with prominent and excessive trabeculations with deep recesses in the ventricular wall. LVNC is an increasing recognized cause of heart failure with high risk of thromboembolic events, arrhythmia, and sudden cardiac death. The pathogenic mechanism is associated with certain genetic mutations, such as TNNT2, TAZ, DMD etc., but the non-genetic LVNC is also found in the athletes, pregnancy, or the patients with chronic renal failure. The prognosis of LVNC is poor, particularly in those with onsets during infancy. The state-of-the-art therapy for LVNC patients with heart failure limited in symptom relief by anti-congestive medications (diuretics, ACE inhibitors, and beta-blockers) and antiplatelet therapy to prevent thrombo-embolism. The unmet medical need is to develop the personalized medicine for LVNC.

In Dr. Wen-Pin Chen’s previous study, their major breakthrough finding is to identify Simvastatin as a precision medicine for LVNC therapy. They found Simvastatin can significantly improve cardiac function not only in human cardiomyocytes derived from LVNC patients’ iPSCs in vitro and LVNC mice in vivo but also in the bedside of the probands with off-label-use Simvastatin for heart failure treatment. The mechanistic study revealed that the novel drugs acting through downregulating EZH2 expression in LVNC cardiomyocytes are a promising drug action model for developing novel drugs against heart failure progression in LVNC.