Guest Post – Michelle Ta, PhD Student
I first came across polycystic kidney diseases (PKD) during the summer of 2010, when I decided to undertake some laboratory work at Macquarie University. Under the supervision of Professor Jacqueline Phillips, I stained kidney tissue to determine whether there are regions that are deprived of oxygen within polycystic kidneys. This sparked my curiosity in PKD. I was simultaneously amazed and baffled by the phenomenon that is cyst growth – what causes these cysts to form, and can we target any biological ‘pathways’ using particular drugs? These questions led me to undertake postgraduate research in PKD with Associate Professor Gopala Rangan and Professor David Harris at the Westmead Institute for Medical Research.
My current research focuses on inflammation in PKD. In simple terms, inflammation is the body’s response to injury or infection. It is an immune response and a feature of diseases such as rheumatoid arthritis. Interestingly, inflammatory cells have been commonly identified in PKD, but little is known about whether or how they contribute to the disease. I am investigating a particular system that controls inflammatory genes and cell growth. I studied a drug that targets this inflammatory system, administering it to rats with a disease that is similar to human autosomal recessive PKD (ARPKD). Using magnetic resonance imaging (MRI), we found the drug reduced kidney size and cyst size. These findings are exciting since in human PKD, larger kidney volumes are associated with worse kidney function (i.e. failure of the kidneys to filter urine).
The next part of my research focussed on working out exactly how the drug compound decreased cyst size. I subsequently found that the drug slows down the growth of cultured human PKD cells. Unfortunately though, the drug did not help to slow the decline in kidney function in our animal study. Despite these limitations, these results add to the growing body of research on inflammation in PKD, and emphasise that some basic aspects of PKD biology are still not well understood.
I am fortunate to be supported by the Michael Stern scholarship. This scholarship was set up by the Stern and Gardos families in memory of Dr. Michael Stern, a radiologist and PKD patient who was treated at Westmead Hospital. It has been very humbling to meet members of the Stern family and understand the impact of this disease on a human and emotional level. It reiterated to me the importance and urgency of finding a cure for PKD. At the moment we only have medications to control some of the symptoms of the disease (such as high blood pressure), but not to treat the disease itself. Consequently, many patients must resort to dialysis or transplantation.
The past few years have seen some exciting developments in investigating therapies for PKD. Such drug candidates include sirolimus (an immunosuppressant used during organ transplantation) and tolvaptan (a drug used to increase blood sodium levels in conditions such as heart failure). There remains much to be done, both at the ‘bench’ level to understand the basic biology of PKD, and at the ‘bedside’ level to trial new treatments in patients. I am glad that my research has contributed to our scientific knowledge of PKD, and in the future I hope to be involved in bringing potential therapies to the clinical level.