Discovery of Novel, Early Response Biomarkers for Trials in ADPKD
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a devastating disease with limited treatment options. Few drugs have been tested in clinical trials, and only one has been approved. The major barrier to ADPKD drug development is the lack of an early response biomarker, meaning an indicator of clinical response to an intervention that can be used to assess the efficacy of a drug expeditiously (commonly known as clinical proof of concept). This step is critical in determining whether to move forward with development of a drug and invest substantial money and time in the much larger and longer clinical trial required to obtain regulatory approval. The overall goal of this proposal is to identify candidate response biomarkers using a broad-based, discovery approach. This addresses a Strategic Goal of the Polycystic Kidney Disease Topic Area, namely, to develop technologies for tracking progression of associated diseases and conditions. Because a project of this scale is not feasible in patients, we will use mouse models of ADPKD, treat them with drugs or genetic manipulation, and screen the entire genome for RNA biomarkers in their kidneys. The goal is to identify one or a small number of candidates that can subsequently be validated in future studies using biospecimens from human clinical trials. If we can find informative response biomarkers that could be used in clinical proof-of-concept studies, this will have a huge impact in the field because it will enable the de-risking and acceleration of ADPKD drug development and thereby expedite the approval of effective therapies for patients with this disorder.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310025
Entities
People
- Alan Yu
Organizations
- United States Army
- University of Kansas Medical Center