Vishal Patel, MD, on Unmet Needs in Polycystic Kidney Disease

“We've gone after the root cause for polycystic kidney disease... People with polycystic kidney disease have mutations in one copy of PKD1 or PKD2, but the other copy is still around in many cells in the kidney. We figured out a way of harnessing that remaining copy and activating it such that it produces more protein. And that, at least in mouse models and human cell lines, seems to slow cyst growth.”

Patients with autosomal dominant polycystic kidney disease (ADPKD) have limited options. The only FDA-approved treatment for ADPKD, tolvaptan, does not address the root cause of the disease and therefore cannot halt its progression.

CGTLive spoke with Vishal Patel, MD, associate professor, Department of Internal Medicine, Division of Nephrology, UT Southwestern Medical Center, about his team’s preclinical research into a potential gene therapy approach to treating ADPKD, which was recently published in Nature Communications. He discussed the unmet needs that currently exist for patients with ADPKD and the limitations of treatment with tolvaptan. He also discussed the genetic basis of ADPKD, highlighting that many patients still have at least 1 functional copy of the disease-targeted genes.

Patel then described the key findings from his team’s research and explained the basic mechanism behind their approach. He also briefly spoke on the potential advantages of the gene therapy approach, which they tested in human cell lines and a mouse model of PKD, if it were to be developed into a new treatment for patient use.

REFERENCE

Lakhia R, Ramalingam H, Chang CM, et al. PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression. Nat Commun. 2022;13(1):4765. Doi: 10.1038/s41467-022-32543-2