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Renovacor and University of Utah Initiate Gene Therapy Research Program for Arrhythmogenic Cardiomyopathy
Robin Shaw, MD, PhD, Professor of Medicine at the University of Utah and Director of the Nora Eccles Harrison Cardiovascular Research and Training Institute, shared his thoughts on the program.
Renovacor will pursue a potential AAV gene therapy for arrhythmogenic cardiomyopathy (ACM) in a research collaboration with the University of Utah’s Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI).1
The research will utilize data previously gathered in a mouse model study carried out by the Shaw Lab, which is led by Robin Shaw, MD, PhD, Professor of Medicine at the University of Utah and Director of the CVRTI. The new collaboration will focus on developing a precision therapy for the 3 largest genetic segments of ACM: plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmoplakin (DSP) associated ACM. A protein previously discovered by University of Utah investigators will be a focal point in the program.
The program aims to develop a therapy that can restore gap junction communication and gap junction protein trafficking between heart and muscle cells. At the moment, there are no available treatments that directly target these trafficking issues in the 3 forms of ACM under study. In the preclinical study, Shaw and colleagues were able to restore gap junction trafficking to the intercalated disc and demonstrate a significant reduction in premature ventricular contractions, which are a major symptom of ACM and can cause potentially life-threatening ventricular arrhythmias.
In an interview with CGTLive, Shaw offered additional perspective on the new program.
CGTLive: What is the focus of the research collaboration?
Robin Shaw, MD, PhD: Our approach is to rescue deficiencies of cardiomyocyte structural and organizational proteins; such occurs in Arrhythmogenic Cardiomyopathy. It is more effective to restore subcellular trafficking highways than to blindly overexpress a key lost protein and hope for the best. The therapeutic protein used in this collaboration organizes the trafficking highways within cardiomyocytes, allowing for key endogenous gap junction communication proteins to arrive at their proper location, limiting cardiac arrythmia. We are rescuing the function of endogenous cardiomyocyte proteins, and of the heart’s electrical system, by restoring the efficiency of internal cardiomyocyte operations.
How does gene therapy address unmet treatment needs for patients with ACM?
Ventricular arrhythmia is one of the highly dangerous manifestations of Arrhythmogenic Cardiomyopathy. To date, we have limited tools to prevent ventricular arrhythmias in these patients. Gene therapy offers the opportunity to “insert” the DNA of full length proteins within heart muscle cells, so we can design a muscle-specific solution to a muscle-specific problem. With Renovacor, we are exploring the effectiveness of the therapy in different genetic subtypes of Arrhythmogenic Cardiomyopathy.
Transcript edited for clarity.