# Innovative Approaches to Treating Alport Syndrome

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $453,731

## Abstract

Project Summary
Kidney disease is worldwide health problem that is becoming increasingly common. Primary glomerular
disease, both genetic and acquired, represents a significant proportion of cases. We are interested in
understanding the makeup of the glomerular filtration barrier and how it becomes damaged, leaky to
plasma proteins, and eventually non-functional. Our focus has been to investigate the composition and
function of the glomerular basement membrane (GBM), a specialized extracellular matrix that is an
integral component of the kidney’s filtration barrier. The GBM contains collagen IV, laminin, nidogen, and
the heparan sulfate proteoglycan agrin, and likely dozens of other less abundant matrix proteins. Although
the GBM is synthesized by both podocytes and glomerular endothelial cells, it is exclusively podocytes
that make the major collagen IV isoform, which consists of the 3, 4, and 5 chains that assemble to
form a secreted heterotrimer. Mutations that affect this collagen IV component of the GBM cause Alport
syndrome, which leads to end-stage kidney disease (ESKD) as well as hearing and eye defects. The
prevalence of Alport syndrome has been estimated to be 1 in 5,000 to 10,000 newborns, so there are
hundreds of thousands of affected patients around the world. Structural GBM abnormalities secondary to
the collagen IV defect lead to thickening and splitting of the GBM and eventually podocyte foot process
effacement, glomerulosclerosis, and tubulointerstitial fibrosis. Until recently there has been no treatment
for Alport syndrome. However, studies in mice and dogs had shown that ACE inhibition slows kidney
disease progression to ESKD. These animal studies have been validated in human Alport syndrome
patients, for whom ACE inhibitors or angiotensin II receptor blockers are now considered the standard of
care. Despite this treatment breakthrough that delays ESKD, it is not a cure; there is still a need for new
targeted therapies. The goal of this proposal is to use innovative, state of the art technologies that involve
small molecule, genetic, and protein biochemistry approaches to attempt to either restore the Alport GBM
to a somewhat normal composition or to alter its composition through removal of pathogenic components.
In either case, the expectation is that improving GBM composition will at least partially normalize GBM
structure and function. Together with renin-angiotensin system blockade as a standard of care, these
treatments should greatly delay the time to ESKD and be beneficial for patients.

## Key facts

- **NIH application ID:** 10375906
- **Project number:** 1R01DK128660-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JEFFREY H MINER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $453,731
- **Award type:** 1
- **Project period:** 2021-09-22 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375906

## Citation

> US National Institutes of Health, RePORTER application 10375906, Innovative Approaches to Treating Alport Syndrome (1R01DK128660-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375906. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*