New drug delivery system may open up treatments for polycystic kidney disease

Researchers who found a way to reach the growth factors that promote cyst growth in polycystic kidney disease, suggest it opens the possibility for repurposing a large number of existing drugs to treat the genetic disorder. A normal kidney is about the size of a fist - a polycystic kidney can grow to the size of an American football.Image credit: Indiana University School of Medicine Polycystic kidney disease (PKD) is the world s most common inherited kidney disease, affecting around 12 million people. About Inderal (Propranolol) It has no known cure. In PKD, fluid-filled, benign cysts develop and grow in the kidneys. About Norlutate (Norethindrone Acetate) without Rx As they accumulate more fluid, the cysts get bigger and bigger and destroy healthy tissue. Cipro (Ciprofloxacin) with no prescription Eventually, this leads to kidney failure, high blood pressure, and other complications. The new study, from the University of California Santa Barbara (UCSB), involves the use of therapeutic antibodies. Buy Arpizole with no prescription These biologic therapies are already used extensively to treat diseases ranging from cancer to autoimmune disorders. Biologic therapies normally use a class of antibody called immunoglobulin-G (IgG) to bind to and prevent the activity of specific proteins or growth factors. But in PKD, the growth factors that drive cyst growth are locked inside the fluid-filled lumen - the central cavity of the cyst - which IgG antibodies cannot enter. The UCSB researchers - led by Thomas Weimbs, a professor of molecular, cellular and developmental biology - found that another class of antibodies called immunoglobulin-A (IgA), were able to penetrate the cyst wall and enter the lumen. Study shows IgA can enter PKD cysts and stay there Three pieces of information came together to spur the discovery made in the study. Buy Rebetol (Ribavirin) with no Rx They arose in earlier work and observations by Prof. Buy Chromium Polynicotinate online Weimbs, who has been working on PKD for 10 years. The first piece of information concerned how IgA could cross a cell layer by binding to polymeric immunoglobulin receptors (pIgR). http://cholesterolreviews.wordpress.com The second, was that a transcription factor called STAT6 appears to be overactive in PKD. And the third, was that Prof. Weimbs remembered that STAT6 had been shown to switch on the expression of pIgRs in other organs. Prof. Weimbs says the "aha" moment came when he brought the three pieces of information together: "I thought if STAT6 is highly active in polycystic kidneys, maybe it also expresses a lot of pIgR - and that turned out to be the case. So we tested this in mouse models and in human polycystic kidney tissues, and, in both cases, high levels of pIgR were expressed in kidney cysts." When they injected IgA into mice with polycystic kidneys, the team found around 7% of the injected IgA stayed inside the cyst lumens. Prof. Weimbs says this suggests some IgA gets taken into the cysts - and because there is no way for it to exit - it remains trapped: "So we end up with a way of exploiting the pIgR system for targeting these antibodies specifically to the polycystic kidney." A key step remains to be tested before the possibility that the method opens up new treatment avenues for PKD becomes a likelihood - and that is to find a way to reformat IgG antibodies into IgA types so they can enter the cyst using the pIgR system and target the growth factors. Should this step be successful, then, according to Prof. Weimbs: "Our strategy allows for the repurposing of thousands of existing monoclonal antibodies that have already been developed, which opens up a whole new class of therapeutics not previously used for PKD therapy." Meanwhile, Medical News Today has learned how another team, reporting in the Journal of the American Society of Nephrology, may also have developed a new way to treat PKD by targeting blood vessels surrounding cysts. Written by Catharine Paddock PhD