Therapeutic area: Muscular Disorders, Cardiomyopathy
Disease: Dilated Cardio Myopathy
Monogenic inroad: TITIN
Cellular Model: Patient-derived cardiomyocytes (ventricular)
Project Origin: Technische Universität München, Klinikum rechts der Isar, Prof. Karl-Ludwig Laugwitz & University of Göttingen, Prof. Wolfram Zimmermann
Medical need: With a prevalence of 4:10,000, Dilated Cardio Myopathy (DCM) is the most common hereditary heart disease. It is characterized by chamber dilatation with thinned chamber walls, combined with a reduction in the ejection fraction. DCM usually leads to the clinical picture of heart failure. The only curative therapy so far is cardiac transplantation, which is limited to severely symptomatic DCM patients. DCM is often familial, and the most common genetic predisposition is a truncating variation in the giant sarcomeric protein, titin, which occurs in up to 15% of ambulant patients with DCM and 25% of end-stage or familial cases.
Goal: The program aims for development and implementation of a phenotypic approach exploiting a physiologically highly-relevant disease model in assay format. The assay goes with a tailored AI-based image analysis tool and will be used for the identification of new targets and small molecules targeting the sarcomere stability in cardiomyocytes derived from dilated DCM patient-specific iPSC.
Development stage: Pharmacological assay validation and automation