Clinical development of a monoclonal antibody-based therapeutic targeting polycystic kidney disease.
There are various supportive treatments that can be used to control the symptoms of PKD, to help prevent or slow down the loss of kidney function. However, there are currently no treatment options to prevent cysts developing or reverse the process once formed. As such, there is currently no cure for PKD, where the only options to treat kidney failure are dialysis or organ transplantation.
Our recent discovery has identified a novel protein, called WISP1, that may play an important role in the formation of kidney cysts and the detrimental scarring of the kidneys that leads to reduced kidney function over time. The successful completion of these studies will unravel the role that WISP1 plays in both cyst growth and kidney scarring. Moreover, we will develop a protein that inhibits WISP1 protein production that will be used therapeutically to retard cyst growth and slow or alleviate disease progression.
Dr Gopi Rangan- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney
Role of DNA damage signalling in Autosomal Dominant Polycystic Kidney Disease.
This project will determine if stopping damage to the genetic coding material (called DNA) reduces the formation of kidney cysts in polycystic kidney disease.
Professor John Shine- Molecular Genetics of Inherited Kidney Disorders, Garvan Institute of Medical Research, Sydney
Identifying novel mutational mechanisms in the genetic pathogenesis of PKD.
ADPKD is the most common genetic kidney disorder – it causes cysts to develop within the kidney, which eventually destroy the normal kidney tissue and lead to renal failure in many patients. Despite how common the disease is there are still many gaps in our understanding. In many families we still cannot identify the genetic cause of their disease and there remain questions about the reason kidney cysts develop and destroy the kidney. Our project will use the latest in genetic sequencing technologies, called Whole Genome Sequencing, to identify new genetic causes of ADPKD. Understanding new mechanisms will help in better understanding this complex disease and to develop ways to slow and treat ADPKD.
* This Project is funded in partnership with the PKD Foundation USA
A novel genetic test for ADPKD – A new genetic sequencing technique which has shown promising results was previously trialled and now requires testing a larger study.
Partnering with the Mayo Clinic, this grant will work to test this with patients who have been sequenced by more established methods. It is anticipated that comparing the two methods will show the new test to be more detailed and accurate and to establish it as the lead genetic test for PKD in Australia. This will result in improvements for patients and assist with understanding underlying causes and to find a cure.
Professor Jacqueline Phillips, Macquarie University, Sydney
Genes and cellular stress in PKD- This grant will investigate how PKD genes can cause an increase in stress signals in kidney cells that drives cell damage and progression of kidney disease.
These same processes can also be driven by the build-up of toxins in the blood that arises when kidney function declines and this project will further test if the combination of PKD mutation and toxins worsens the stress response in the cell. Determining how PKD leads to cell damage has the potential to change the way we treat patients from symptomatic to strategically targeted.
Dr Bo Wang, Monash University, Melbourne
The therapeutic potential of miRNA-based MAPK inhibition to slow the progression of PKD
Several therapeutic interventions have been designed specifically to inhibit cell proliferation in a variety of animal models of PKD. A cell signal–regulated kinase (MAPK) inhibitor is shown to effectively block cyst growth and kidney enlargement, and to preserve kidney function.
Recently, a unique microRNA was discovered that is important in regulation of gene expression and can slow down the over proliferation of kidney cells that lead to cyst formation. The project will investigate the mechanisms of microRNA in maintaining normal kidney cell function that will result in reduced cyst growth. The study will provide a novel target for PKD treatment with a high potential for clinical translation.
Dr Annette Wong, Westmead Institute for Medical Research, Sydney
Validation of copeptin as a prognostic molecular biomarker in patients with CKD stages 1 – 3 due to ADPKD- Predicting patients at high risk of kidney failure who therefore require medical follow-up is important however, currently there are no blood tests to provide this information.
Vasopressin is a natural hormone in the body that may cause kidney cysts to grow bigger. In the past it has been difficult to measure vasopressin but it can now can be measured easily using a test for copeptin. This project will determine if a simple blood and/or urine test for copeptin can help predict this risk in patients with early-stage ADPKD.