RECARDIO’s Cardiac Therapy: Scientific and Medical Rationale
Regenerative therapies for the treatment of patients with cardiovascular diseases have the potential to improve cardiac function, quality of life and survival.
First regenerative therapeutic approaches started with research, which demonstrated initially that granulocyte-colony stimulating factor (G-CSF) treatment after MI increases the release and migration capacity of bone marrow stem cells into ischemic tissue. Stromal cell-derived factor-1 (SDF-1) represents the major chemokine for initiating stem cell migration and homing to the site of ischemia with consecutive neovascularisation, activation of residual cardio-blasts and anti-apoptotic pleiotropic effects.
Accordingly, local increase of SDF-1 represents a promising approach to treat ischemic disorders. Safety concerns and the need of invasive transplantation protocols limit strategies to augment SDF-1 gene expression and protein delivery in the ischemic myocardium.
The alternative to increase SDF-1 concentration in the injured heart is the inhibition of CD26/DPP-IV (dipeptidyl-peptidase IV), which is responsible for cleavage and inactivation of SDF-1. Early preclinical data demonstrated that DPP-IV-inhibition improves survival and myocardial function after infarction by increasing regenerative capacity, especially, when administered in combination with G-CSF, which was confirmed in large animal studies by RECARDIO.
RECARDIO’s proprietary, patented and drug based therapeutic concept is therefore the acute administration of the inlicensed dutogliptin, a small molecule DPP-IV inhibitor, leading to a significantly increased regenerative effect in the ischemic cardiac tissue. Targeting this mode of action ameliorates cardiac remodeling with the long term benefit goal of reducing morbidity and increasing survival.
1. Zaruba, M. M., Theiss, H. D., Vallaster, M., Mehl, U., Brunner, S., David, R., Fischer, R., Krieg, L., Hirsch, E., Huber, B., Nathan, P., Israel,L., Imhof, A., Herbach, N., Assmann, G., Wanke, R., Mueller-Hoecker, J., Steinbeck, G. and Franz, W. M. (2009).
Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction.
Cell Stem Cell 4, April 3 2009.
2. Steinhauser M. L., Lee R. T. (2009)
Cardiovascular Regeneration: Pushing and Pulling on Progenitors
Cell Stem Cell 4, April 3, 2009