Researchers from the University of Texas Southwestern (UTSW) Medical Center reported a new study aimed at developing a strategy for gene therapy with the potential to arrest or cure autosomal dominant polycystic kidney disease (ADPKD) that blocks the inhibition of PKD1 and PKD2 gene expression by deleting a binding site for microRNAs inhibited the formation and growth of kidney cysts in animal models.

The findings of the study published in the journal Nature Communications recently give a new ray of hope to millions who suffer from the condition, which is the most common genetic cause of kidney failure across the world where the patients usually inherit one mutated copy of PKD1 (or PKD2) and one normal copy of the genes.

“For more than 25 years, we have known that ADPKD is caused by mutations of PKD1 or PKD2 genes. Yet, no therapeutic strategy exists to go after these root causes,” said Dr Vishal Patel, Associate Professor of Internal Medicine in the Division of Nephrology at UTSW and corresponding author of the paper.

In ADPKD, multiple small fluid-filled sacs called cysts are formed in the kidney when the levels of the polycystin 1 and 2 proteins fall below the critical threshold  the researchers due to the failure of the normal copy of the gene to produce these proteins in enough quantities, the researchers of the study said.

At one end of the gene’s messenger ribonucleic acid (mRNA), there is a region of code that helps protect it from degradation but can also control how much of the protein is made and the binding of microRNAs to this region of the mRNA code can block the protein production resulting in a fall in the protein levels, they added.

Since PKD1 contains a binding site for miR-17, the microRNA is active in models of ADPKD that looked into the fact that if blocking the binding of miR-17 to PKD1 could prevent kidney cyst formation.

Results obtained after deletion of the miR-17 binding site from PKD1 mRNA in cell cultures and an ADPKD mouse model indicated that deletion of the binding site increased stability of the mRNA strand, raised Polycystin-1 levels, and decreased kidney cyst growth.

The researchers further found that blocking miR-17 binding to PKD1 mRNA with an anti-miR-17 drug after cyst formation also decreased cyst growth, indicating that this interaction could be a promising target for polycystic kidney disease (PKD) treatment.

“There are numerous genetic conditions where one copy of the causative gene is mutated, but the other copy is still normal. Our approach to harnessing the remaining normal copy is likely applicable to many other diseases besides PKD,” Dr Patel said.