Toward Personalized Therapy for Polycystic Kidney Disease
Abstract
Autosomal dominant polycystic kidney disease (ADPKD), the most common life-threatening genetic disease, affects over 600,000 individuals in the United States alone and more than 12 million people worldwide. The disease is characterized by the development of bilateral enlarged epithelial-lined cysts in the kidney, which ultimately leads to renal failure in half of the patients. In addition, patients have a five-fold higher risk to aneurysms than the general population, and other extrarenal abnormalities in the vasculature, pancreas, and liver. Hypertension is a common early finding in ADPKD, occurring before any significant reduction in renal function. In a significant subset of patients, the mutated genes are able to make proteins, but these mutant proteins are not able to get to where they normally function. We hope to develop reagents to study the mutations found in human patients and use them to screen for small molecules that correct the trafficking of the disease proteins. Our goal is to identify small molecules that redirect the disease proteins to the normal functional sites. These small molecules may restore some of the normal functions of the disease proteins in patients with trafficking mutations and slow the disease progression. These experiments will likely provide putative new therapeutics for reducing the risk of hypertension and renal failure in specific patient population and provide us important tools for elucidating how the disease proteins work.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610617
Entities
People
- Jing Zhou
Organizations
- United States Army