徐放性プロスタサイクリン作動薬を用いたCell-Free型再生医療の重症心不全への応用

抄録

Regenerative therapy by cell transplantation is the promising treatment for advanced cardiac failure. Therapeutic mechanisms underlying this treatment has been shown to be the paracrine effects, in which the transplanted cells induced a sustained upregulation of a variety of cytokines, predominantly proangiogenic cytokines, in the damaged cardiac tissue to enhance the native regenerative capacity and thus to yield the therapeutic effects. Considering the limitation in cell transplantation therapy, a “shelf-stored” drug, in any, which induce up-regulation of proangiogenic cytokines in the cardiac tissue, would be an ideal solution for widespread application of cardiac regeneration therapy. ONO-1301, which is a synthetic prostacyclin agonist with thromboxane A2 synthase inhibitory activity, has been shown to act as a multiple-cytokine inducer by ligating IP receptor expressed in the endothelial cells, vascular smooth muscle cells or fibroblasts. In addition, ONO-1301 is chemically stable compared to commercialized prostagrandin agonists, such as illoprost or beraprost, and therefore be promised as the drug for chronic pathologies. We developed polymerized form of ONO-1301, YS-1402, as a slow-releasing drug for treating advanced cardiac failure, In this review, we document pharmacological activity of ONO-1301/YS-1402, results of preclinical studies and protocol of following first-in-human investigator initiated clinical study.