Developing novel drug for acute MI, acute kidney injury, and subsequent chronic organ failure: Study
Acute myocardial infarction and acute kidney injury are life-threatening conditions caused by ischemia, resulting from reduced or blocked blood flow to organs. Although early restoration of blood flow improves survival, many patients still develop chronic heart or kidney failure. The mechanisms driving this transition from acute tissue injury to chronic dysfunction remain poorly understood, and effective treatments are lacking.
In this study, researchers focused on the immune receptor CD300a, which suppresses immune cell activation. Using a mouse model with genetic deficiency of CD300a, they investigated the progression from AMI and AKI to chronic heart and kidney failure. The findings revealed that CD300a deficiency attenuated cardiac dysfunction caused by AMI and reduced subsequent cardiac fibrosis, thereby preserving cardiac function. Similarly, renal dysfunction following AKI was less severe, renal fibrosis in chronic kidney failure was diminished, and renal function was maintained.
The mechanism underlying these protective effects is as follows: in ischemic heart and kidney tissues, CD300a deficiency enhanced macrophage-mediated phagocytosis of dead cells, reducing inflammation. Moreover, in CD300a-deficient mice, SiglecF-/lo neutrophils exhibited increased production of angiogenic and antifibrotic factors, which inhibited progression to chronic organ failure. Importantly, administration of neutralizing antibodies against CD300a in mice produced outcomes comparable to those observed in CD300a-deficient models, suppressing the progression to chronic heart and kidney failure.
The research group now aims to evaluate the efficacy and safety of humanized anti-human CD300a neutralizing antibodies in clinical studies, with the ultimate goal of developing novel therapeutic agents for acute tissue injury and subsequent chronic organ failure in the heart and kidney.
Reference:
Nanako Nishiyama, Hitoshi Koizumi, Chigusa Nakahashi-Oda, Satoshi Fujiyama, Xuewei Ng,Hanbin Lee, Fumie Abe,CD300a immunoreceptor regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney, Journal of Clinical Investigation, DOI:10.1172/JCI184984
