Development of Novel Therapeutic Strategies to Prevent the Development of Kidney Disease

Abstract

We provide a research update regarding novel therapeutic strategies to prevent the development of kidney disease and summarize the latest proceedings in this field. Chronic progressive kidney disease carries severe consequences and has limited treatment options. The purpose of this review is two-fold. The first aim is to provide a concise overview of the strategies of gene therapy, including pyrrole-imidazole polyamides (PI polyamides). PI polyamides are a new type of small compound that inhibit gene expression by binding to the minor groove of DNA. A PI polyamide that targets rat transforming growth factor-β1 was designed as a gene-silencing agent for progressive kidney disease. In the future, control of gene expression by PI polyamides may ameliorate progressive kidney diseases that are not treatable with current medicine. Future therapeutic strategies aimed at alteration of the immune responses through manipulation of Fcγ receptor interactions by the use of PI polyamides could be explored in the model of lupus nephritis. Thus Fcγ receptor gene therapy provides an attractive strategy to develop an immunotherapy as a general treatment option. The second aim is to summarize the published data regarding the role of bone marrow stem cells in renal repair after acute and chronic kidney injury. Currently, much of our knowledge of renal protective effect of dedifferentiated fat (DFAT) cells is obtained through animal research. The results to date indicate that DFAT cells may provide a source for cell therapy for severe progressive kidney disease. Our goal is to understand the mechanism of renal protection by DFAT cells and to develop stratagems utilizing DFAT cells for the eventual treatment of patients with kidney disease. The importance of conservative regenerative medicine has recently been demonstrated. It has become apparent that angiotensin II receptor blockade (ARB) improves the proliferation and function of endothelial progenitor cells in hypertension, suggesting that ARB is useful to repair hypertensive renal injury. In this review, we will focus on the role of gene therapy and regenerative medicine as therapeutic modalities in kidney disease.