A potential new drug therapy for patients with kidney diseases has been discovered by scientists at the Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute at UCSB.
Statistics show that over 600,000 people in the U.S and 12 million worldwide are affected by the inherited kidney disease known as autosomal-dominant polycystic kidney disease (ADPKD), which is characterized by proliferation of cysts that damage the kidneys, causing kidney failure in half of the patients by the age of 50.
Currently, no treatment exists to prevent or slow the cyst formation and most ADPKD patients require kidney transplants or lifelong dialysis for survival, says Thomas Weimbs, Associate professor in the Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute at UCSB.
First, Weimbs and his research team discovered a molecular mechanism that sheds light on the disease. The mechanism concerns polycystin-1, a protein that is mutated in ADPKD patients. They found how this protein regulates a well-known transcription factor called STAT3. Transcription factors transcribe information from DNA to RNA, from specific genes. Second, the team discovered that STAT3 is strongly and aberrantly activated in polycystic kidneys.
"The clinical significance of these discoveries lies in the fact that STAT3 is also known to be aberrantly activated in many forms of cancer and is considered an important drug target for cancer therapy," said Weimbs.
"Numerous STAT3 inhibitors are currently being developed and tested, and several experimental drugs are already available. Our results suggest that STAT3 activation is a driving force for the cyst growth that leads to polycystic kidneys in ADPKD. Therefore, STAT3 may be a highly promising drug target for the treatment of ADPKD," he added.
Weimbs explained further that STAT3 is a signaling molecule that is activated in response to many different growth factors binding to specific receptors on the surface of kidney cells. In response to these growth factors hitting the cell, STAT3 is activated. That causes STAT3 to turn on the expression of certain genes. This activity causes the cells to proliferate, as they do in cancer.
The research is published in the Proceedings of the National Academy of Sciences.