New UCLA research using mouse models and human genetic data has uncovered a critical factor in kidney scarring, offering a promising precision medicine approach to prevent chronic kidney disease progression.
Published in Science Translational Medicine, the study highlights the role of type 5 collagen—a minor component of scar tissue—in kidney fibrosis.
Researchers demonstrated how an experimental therapy might prevent kidney failure in high-risk individuals.
Chronic kidney disease (CKD) affects over one in seven U.S. adults and 800 million people worldwide.
It can result from diabetes, high blood pressure, and kidney stones. CKD progressively impairs kidney filtration due to excessive fibrosis, and currently, no therapies directly reverse this process.
The study found Differences in type 5 collagen expression determine the extent of kidney scarring after injury. Analysis of the UK Biobank revealed Col5a1 expression correlates with chronic kidney disease risk.
\In mouse models, low Col5a1 expression led to more severe fibrosis and faster kidney failure. Type 5 collagen structures scar tissue in an organized way; lack of it triggers a cycle of excessive fibrosis.
Researchers tested Cilengitide, a drug originally designed for cancer treatment. It disrupts αvβ3 integrin signaling—the pathway responsible for sensing disorganized scar tissue and driving excessive fibrosis.
Cilengitide reduced kidney fibrosis and slowed disease progression in mice with low Col5a1 expression, but had no effect in mice with normal expression—suggesting strong precision medicine potential.
Deb’s team is developing a blood test to measure Col5a1 levels in human CKD patients. This test could help identify patients most likely to benefit from integrin-targeting therapies. Researchers are also exploring fibrosis mechanisms in liver and vascular tissues.
The use of Cilengitide for kidney fibrosis has not yet been approved by the FDA. However, the safety data from earlier cancer trials and new preclinical evidence support its potential for repurposing.
The study is published in Science Translational Medicine.
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