The Department of Biomedicine
BBB seminar

BBB seminar: Seppo Ylä-Herttuala

Gene therapy for cardiovascular diseases – From bench to bedside

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Seppo Ylä-Herttuala
A.I. Virtanen Institute, University of Eastern Finland, and Gene Therapy Unit and Science Service Center, Kuopio University Hospital, Kuopio, Finland

Therapeutic vascular growth is a potentially useful strategy for ischemic heart disease and peripheral arterial occlusive disease. It involves generation of new capillaries, collateral vessels and lymphatic vessels in ischemic muscles using either recombinant growth factors or their genes. Arteriogenesis is a process caused by increased sheer stress at the arteriolar level resulting in the formation of large conduit vessels from preexisting small vessels, whereas angiogenesis and lymphangiogenesis refer to generation of new vascular structures in vivo. Most commonly used growth factors for therapeutic angiogenesis are members of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) families. Some other cytokines and growth factors can also have angiogenic effects. Improved perfusion and functional parameters can be achieved by angiogenesis and arteriogenesis in large animal chronic ischemia models and in man. Safety of the clinical gene therapy of cardiovascular diseases has been excellent with long-term follow-up to 10 yrs after the therapy. Small non-coding RNAs can also be used for angiogenic gene therapy. Most promising results have so far been obtained with direct catheter-based intramyocardial injections of VEGF-D genes with adenovirus and AAV vectors.

Selected references:

Ylä-Herttuala S, Bridges C, Katz MG, Korpisalo P. Angiogenic gene therapy in cardiovascular diseases: dream or vision? Eur Heart J (2017) 38:1365-71

Hartikainen J, Hassinen I, Hedman A, Kivelä A, Saraste A, Knuuti J, Husso M, Mussalo H, Hedman M, Rissanen TT, Toivanen P, Heikura T, Witztum JL, Tsimikas S, Ylä-Herttuala S. Adenoviral intramyocardial VEGF-D∆N∆C gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up. Eur Heart J (2017) 38: 2547-55

Chairperson: Helge Wiig, Department of Biomedicine