Targ-CD39, a fusion protein targeting activated platelets, strongly reduced infarct size and restored cardiac ejection fraction to pre-injury levels in a mouse ischemia/reperfusion model.
Does Targ-CD39 protect from cardiac ischaemia/reperfusion injury and preserve cardiac function in a mouse model?
A novel fusion protein targeting CD39 to activated platelets protects against myocardial ischaemia/reperfusion injury and preserves cardiac function in mice.
Absolute Event Rate: 0% vs 0%
Aims: CD39 is a cell membrane NTPase with anti-inflammatory and anti-platelet effects. However, its clinical use is limited by its bleeding side effect. With the goal of harnessing its therapeutic potential while avoiding haemostatic problems, we designed a fusion protein consisting of the extracellular domain of CD39 and a single-chain antibody (Targ-CD39) that specifically binds to activated glycoprotein (GP)IIb/IIIa and thus to activated platelets. Through this enrichment at activated platelets, the required systemic dose is below the dose impairing haemostasis. Methods and results: Using an ischaemia/reperfusion mouse model (left anterior descending artery ligated for 1 h) we achieved remarkable protection of the reperfused tissue with Targ-CD39 compared with Non-targ-CD39 (mutated, non-binding version of Targ-CD39) and PBS control. Targ-CD39 restored ejection fraction and fractional shortening to a level indistinguishable from pre-injury status, while controls showed functional deterioration. Employing advanced clinically relevant methods of ultrasound analysis, we observed that both radial and longitudinal strain and strain rate showed infarct-typical changes of myocardial deformation in controls, but not in Targ-CD39 treated mice. Histological assessment confirmed strong reduction of infarct size and increase in neovascularization. Furthermore, attenuation of post-ischaemic inflammation was seen in cytokine profiling. Conclusion: Overall, we demonstrate that Targ-CD39 holds promise for treatment of myocardial infarction.
Ziégler et al. (Tue,) reported a other. Targ-CD39, a fusion protein targeting activated platelets, strongly reduced infarct size and restored cardiac ejection fraction to pre-injury levels in a mouse ischemia/reperfusion model.