Modelling hereditary kidney disease using induced pluripotent stem cells: determining genetic mechanisms and developing novel targeted therapies

Alport syndrome is a genetic kidney diseases that affects one in 10,000 individuals and occurs as a result of collagen IVα5 (COL4A5) mutations that affect kidney podocytes. Podocyte depletion is a hallmark of kidney injury, which ultimately leads to end-stage renal failure (ESRF), and for which there is currently no cure (1). Currently, there are no predictive disease models for Alport syndrome and other inherited kidney disorders, which imposes significant challenges for clinicians to provide effective and targeted therapies for these vulnerable patients. However, the recent discovery of adult cell reprogramming to generate induced pluripotent stem (iPS) cells (2) provides an unprecedented opportunity to elucidate disease mechanisms in vitro, to provide tools for understanding how mutations cause disease, to develop disease modifying bioassays, and to advance cell replacement therapy. We will use iPS cell technology to develop an in vitro, long-term and self-renewing cellular model of X-linked Alport syndrome. This model will facilitate the development of effective treatments to correct diseased podocytes, and provide a robust platform for the development of new therapeutic interventions for inherited kidney disorders.