�Nephrology physician-scientists at the University of Miami Miller School of Medicine have discovered a critical pathway of a commonly used immunosuppressant drug, cyclosporine. The finding, made by Peter Mundel, M.D., professor and director of the Miami Institute of Renal Medicine, Christian Faul, Ph.D., help professor of medicine in the Division of Nephrology and Hypertension, and Jochen Reiser, M.D., Ph.D., professor of music and top dog of the Division of Nephrology and Hypertension, will make it possible to identify drugs that contain the benefits of cyclosporine in treating kidney disease, without its long-term ill effects.
The uncovering has been published in the September issue of the premier research daybook Nature Medicine.
The scientists, who of late left Mount Sinai School of Medicine and Harvard Medical School to join the Miller School, have shown a completely newfangled mechanism for the reduction of urinary protein loss by cyclosporine A (CsA). Cyclosporine A is known as an immunosuppressant drug used in organ organ transplant for its ability to inhibit T cell single-valued function through the inhibition of calcineurin signal. It is also used in kidney disease to treat patients who have protein in the urine, a status that is, among others, a serious risk for cardiovascular last.
In many kidney diseases, it is common to see the dysfunction of podocytes, cells that live in the lining of the kidney which ar responsible for filtering protein. When the podocyte function breaks down, there is a massive loss of protein in the pee, a condition known as proteinuria.
For many long time, scientists believed that cyclosporine's antiproteinuric effect centered on its ability to keep out down the signaling of T cells, just as it does as an immunosuppressant. Instead, the research by the three UM scientists and nine other researchers indicates that cyclosporine works as an antiproteinuric due to its manoeuver effect on the podocyte actin cytoskeleton.
"Our inquiry shows a new mechanism," says Mundel, the study's principal investigator. "This finding has large clinical implications." He explains that scientists now have a new avenue for finding new drugs that avoid the side personal effects of long-run use of cyclosporine in treating kidney disease, which can include the deprivation of kidney function itself.
Mundel says doctors frequently don't sympathize how prescribed drugs really work on patients. "This study not only describes the mechanics of cyclosporine in the kidney," says Mundel, "it also sheds light on the pathogenesis of proteinuric diseases in general, suggesting that the immune scheme is much less important for this type of disease than anticipated." Mundel says this understanding has great potency to treat proteinuria. Most importantly, synaptopodin, a protein Mundel has been working on for more than two decades, was institute in this study to be a direct butt of cyclosporine. This discovery will allow researchers to develop novel antiproteinuric drugs that quash the serious side effects of long-term CsA discussion.
This is the second article from this new group of UM nephrologists published in Nature Medicine within eight months. In a previous study light-emitting diode by Reiser (Wei et al. Nat Med. 2008 Jan; 14(1):55-63.), they showed that functions of podocytes can be directly modified in a positive way by novel experimental drugs, a discovery that could lead to patient habit very presently.
Reiser sees these 2 studies as solid building blocks for their go ahead. "We have establish that these new discoveries will provide us to find new drugs to treat proteinuria and more effectively aid our patients in the near future," says Reiser. The Division of Nephrology and Hypertension recently constituted the Miami Institute of Renal Medicine, which houses a Drug Discovery Center that will focus on the development of kidney-specific drugs. "We are very excited to be hither," says Reiser, "working in a squad effort to turn our research into practical applications that benefit patients."
University of Miami Miller School of Medicine
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