# Obeticholic acid as a novel treatment for Alport syndrome

> **NIH NIH F30** · GEORGETOWN UNIVERSITY · 2023 · $52,694

## Abstract

PROJECT SUMMARY / ABSTRACT
 Current treatment options for Alport syndrome are extremely limited: Alport syndrome is a hereditary
orphan disease arising from defects in the collagen IV α3α4α5 heterotrimer, and it invariably results in chronic
kidney disease (CKD). A kidney transplant is the definitive cure for CKD arising from Alport syndrome, but the
need for kidney donors far exceeds the availability. Renin-angiotensin-aldosterone system (RAAS) blockade,
such as the drug ramipril, is the pharmacological mainstay used to treat CKD in patients with Alport syndrome.
Bardoxolone methyl (BdMe) is a promising investigational drug that is very close to being approved to treat
Alport syndrome. Nevertheless, developing additional therapies for Alport syndrome is critically important.
 Farnesoid X receptor (FXR): FXR is a nuclear receptor that is highly expressed in the kidneys, liver,
adrenals, small intestines, and vasculature. It is endogenously activated by bile acids. Obeticholic acid (OCA)
is a specific FXR agonist that is already approved by the FDA. Thus, OCA could be repurposed to treat
Alport syndrome if it is shown to be effective. Importantly, OCA has been shown to be protective in many other
models of chronic kidney disease.
 The OVERARCHING GOAL OF THIS PROPOSAL is to investigate OCA as a novel treatment for Alport
syndrome using a transgenic mouse model. We will test the hypothesis that OCA treatment, with or without
coadministration of either ramipril or BdMe, is nephroprotective in a mouse model of Alport syndrome. These
combinations were chosen in part because evidence in other models of kidney disease suggests that OCA
may work through similar pathways as ramipril and BdMe. Thus, it is plausible that OCA could potentiate the
beneficial effects of ramipril and BdMe. This may occur independently of any other beneficial effects of OCA.
 In addition, we will investigate levels of FXR and its well-defined target genes in renal biopsies from
patients with Alport syndrome. Label-free imaging will be performed to quantify fibrosis and metabolism, and
their correlation with FXR expression will be investigated with spatial resolution within the same biopsy.
Correlations will also be sought between these data and the clinical metadata associated with each biopsy.

## Key facts

- **NIH application ID:** 10693277
- **Project number:** 5F30DK129003-03
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Bryce Alan Jones
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $52,694
- **Award type:** 5
- **Project period:** 2021-08-30 → 2025-08-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693277

## Citation

> US National Institutes of Health, RePORTER application 10693277, Obeticholic acid as a novel treatment for Alport syndrome (5F30DK129003-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10693277. Licensed CC0.

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