Nephrology, Rare/Orphan
Novel Therapeutics for Proteinuric Kidney Disease
2023 Harrington Scholar-Innovator
A hallmark of most chronic kidney disease is proteinuria, where high levels of protein spill into an individual’s urine. Hypertension, diabetes, and primary proteinuric kidney diseases damage kidney podocytes, epithelial cells that serve as the final barrier to urinary protein loss. Using a genetic model of proteinuric kidney disease, Dr. Campbell has identified a calcium-activated potassium channel, KCa3.1, which becomes upregulated in injured podocytes and shows potential as a druggable target.
“We uncovered the role of KCa3.1 through transcriptomic profiling of genes that were dysregulated in an experimental model of podocyte injury,” explains Dr. Campbell. “We then performed target validation with human biopsy tissue from patients with proteinuric kidney disease, as well as cell-based functional assays and rodent disease models.”
With Harrington support and guidance in lead compound optimization, Dr. Campbell and his team are conducting proof-of-concept testing with small molecules that inhibit KCa3.1 function. He hopes to demonstrate target engagement and efficacy.
“We are working toward an early-stage treatment to slow disease progression and, ultimately, to be part of a comprehensive management plan supporting overall kidney and cardiovascular health,” Dr. Campbell says.
Podocytopathies and their associated proteinuric kidney conditions account for 90% of all end stage kidney disease in the US, costing $20 billion annually. Hardest hit are African-Americans, who comprise more than 35% of dialysis patients, despite comprising only 13.5% of the population. Latino and Native Americans are vulnerable, also. With the Food and Drug Administration’s (FDA’s) recent acceptance of proteinuria reduction as a surrogate endpoint for protection from kidney function decline in some kidney disease indications, timing is good for new therapeutic drug development.
“Harrington’s expertise and project management support are amazing,” says Dr. Campbell. “We are optimistic about making a positive impact for patients with high unmet clinical need.”