We are developing gene therapy approaches that target the contractile motor protein myosin and the troponin protein complex that controls turning contraction on and off. These gene therapies are tested on muscle cells in culture and in animal models of heart or skeletal muscle disease or myocardial infarct (heart attack). Cell based therapies involve engineering human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CM) that have increased contractile performance and can also deliver a nucleotide that increases contraction to the host myocardium when these hiPSC-CMs are transplanted to a damaged or weakened heart.
- Ruan JL, Tulloch NL, Razumova MV, Saiget M, Muskheli V, Pabon L, Reinecke H, Regnier M, Murry CE. Mechanical Stress Conditioning and Electrical Stimulation Promote Contractility and Force Maturation of Induced Pluripotent Stem Cell-Derived Human Cardiac Tissue. Circulation. 2016 Nov 15;134(20):1557-1567. PubMed PMID: 27737958; PubMed Central PMCID: PMC5123912.
- Moussavi-Harami F, Razumova MV, Racca AW, Cheng Y, Stempien-Otero A, Regnier M. 2-Deoxy adenosine triphosphate improves contraction in human end-stage heart failure. J Mol Cell Cardiol. 2015 Feb;79:256-63. PubMed PMID: 25498214; PubMed Central PMCID: PMC4301986.
- Kadota S, Carey J, Reinecke H, Leggett J, Teichman S, Laflamme MA, Murry CE, Regnier M, Mahairas GG. Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure. Eur J Heart Fail. 2015 Aug;17(8):772-81. PubMed PMID: 25876005.
- Kolwicz SC Jr, Odom GL, Nowakowski SG, Moussavi-Harami F, Chen X, Reinecke H, Hauschka SD, Murry CE, Mahairas GG, Regnier M. AAV6-mediated Cardiac-specific Overexpression of Ribonucleotide Reductase Enhances Myocardial Contractility. Mol Ther. 2016 Feb;24(2):240-50. PubMed PMID: 26388461; PubMed Central PMCID: PMC4817808.