# Using a small molecule iron transporter to understand and treat FPN1 deficiencies in mice

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $690,022

## Abstract

1. Project Summary / Abstract
 This project aims to develop a “molecular prosthetics” approach for treating diseases caused by genetic
or acquired deficiencies of the iron transporting protein ferroportin (FPN1), known as Ferroportin disease and
Anemia of Inflammation, respectively. Loss of function of FPN1 leads to anemia and/or iron retention in the
liver due to deficiencies in the absorption of dietary iron into the blood and/or the recycling of iron from red
blood cells. This includes a small population of genetically well-characterized patients with loss-of-function
mutations in FPN1, as well as >10 million patients with autoimmune disorders, such as rheumatoid arthritis,
inflammatory bowel disease, Celiac disease, and systemic lupus erythematosus, who suffer from acquired
deficiencies of this same protein. Currently available treatments, including regular phlebotomy and blood
transfusions fail to address the common underlying deficiency in FPN1 function. Highly collaborative efforts
between our labs led to the discovery of a small molecule natural product isolated from the hinoki tree in
Taiwan, called hinokitiol, that can autonomously transport iron across cellular membranes. We found that iron
gradients build up upstream of the membranes that normally host the missing FPN1 protein, setting the stage
for site- and direction-selective restoration of transmembrane iron transport by this inherently not site- and
direction-selective small molecule. We also found that that this small molecule iron transporter interfaces with
the robust protein-based networks that drive iron homeostasis, creating a molecular bionic-type system.
Preliminary results in leading animal models of Ferroportin disease and Anemia of Inflammation are also very
encouraging. Building on these frontier concepts and extensive preliminary results, we now plan to probe in
depth the effects of genetic and acquired deficiencies of FPN1 in both cells and animals, extensively
characterize the capacity for hinokitiol to replicate the function of the missing FPN1 protein and thereby restore
physiology, and determine the safety of both acute and chronic administration of hinokitiol. These studies
collectively represent a critical next step toward translating this frontier molecular prosthetics approach into a
new clinical treatment for patients suffering from diseases caused by FPN1 deficiencies.

## Key facts

- **NIH application ID:** 9948734
- **Project number:** 5R01HL140526-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Martin D Burke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $690,022
- **Award type:** 5
- **Project period:** 2018-08-06 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948734

## Citation

> US National Institutes of Health, RePORTER application 9948734, Using a small molecule iron transporter to understand and treat FPN1 deficiencies in mice (5R01HL140526-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948734. Licensed CC0.

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