Two discoveries by scientists at the Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute at UCSB indicate that there are possible new drug therapies for patients suffering with kidney disease.

Statistics show that over 600,000 people in the America and 12 million globally are affected by the inherited kidney disease known as autosomal-dominant polycystic kidney disease (ADPKD), which is defined by development of cysts that harm the kidneys and cause kidney failure in almost 50 percent of the patients by the time they reach the age of 50.

Thomas Weimbs, Associate professor in the Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute at UCSB (1), states that there is currently no treatment to prevent or slow down the formation of cysts, and almost all ADPKD patients need kidney transplantation or have to depend on long-term dialysis to survive.

Polycystic kidneys are full of small, benign tumours or cysts, which can have a damaging effect and eventually destroy the kidney, according to Weimbs. The only difference here, compared to cancerous tumours, is that the cysts keep increasing and do not metastasize or attack other tissues.

Firstly, Weimbs and his team of researchers spotted a molecular mechanism that explains the development of the disease. The mechanism involves a protein called polycystin-1, which is mutated in ADPKD patients. They discovered how this protein modulates a familiar transcription factor called STAT3. The role of the transcription factors is to transcribe information from DNA to RNA via specific genes.

Secondly, the research team found that STAT3 is deviantly activated in polycystic kidneys.

Jeffrey J. Talbot, a postdoctoral fellow in the Weimbs lab, explained that STAT3 is a signalling molecule that is alerted in response to various growth factors binding to particular receptors in kidney cells. This is turn activates STAT3, which turns on the manifestation of certain genes. This action causes the cells to multiply, as they do in cancer.

Various STAT3 inhibitors are currently being developed and tested. The team’s results indicate that STAT3 activation is a a key factor for the growth of cysts that leads to polycystic kidneys in ADPKD. Therefore, STAT3 is considered to be a potential drug target for the treatment of ADPKD.

The study, funded by The National Institutes of Health (2), was published in April’s issue of the Proceedings of the National Academy of Sciences.

The research team is presently conducting tests on STAT3 as a drug target in mice with ADPKD.

1) Neuroscience Research Institute
2) The National Institutes of Health