# DFMO Therapy for Polycystic Kidney Disease

> **NIH NIH R41** · RESILIO THERAPEUTICS, LLC · 2020 · $299,934

## Abstract

Abstract: DFMO Therapy for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
 ADPKD is an important human disease affecting 600,000 Americans of all racial and ethnic
backgrounds and accounts for about 10% of all end-stage renal disease (ESRD). We discovered that immune-
based metabolic reprogramming of arginine metabolism in brain disease is based upon an M2-immune
signature that is defined, in part, on arginase over-expression in the arginine to polyamine pathway (Colton et
al. 2006, Kan et al. 2015). Since a similar M2-immune signature was reported in ADPKD and symptoms
improved when the M2-immune signature was removed (Swenson-Fields et al. 2013, Karihaloo et al. 2011,
Yang et al. 2018), these data support that the arginine to polyamine pathway plays an important role in
ADPKD. To test this idea, we measured the ability of difluoromethylornithine, which is an inhibitor of
polyamine synthesis, to change the course of disease in the orthologous Pkd1RC/RC mouse model of ADPKD.
As reported in Fields et al. (2019), we significantly reduced cyst growth and kidney growth and improved other
characteristics of ADPKD with DFMO treatment. Our results with DFMO compare very favorably to similar
results obtained with Tolvaptan treatment in this same model (Hopp et al. 2015). Using a different
inhibitor of the arginine-polyamine pathway and a different mouse model of ADPKD,
Yang et al. (2018) showed similar reductions in cyst and kidney volumes to Fields
et al. (2019) and found improvements in kidney function. With these positive
data in hand, we now propose to confirm or reject the importance of the arginine-
polyamine pathway to ADPKD (Figure 1). Since Pkd1RC/RC mice at 9-months show
decreased kidney function, we propose treating for 9-months with DFMO to inhibit
ODC, with Norvaline (Nva) to inhibit arginase, and with Aminoguanidine (AG) to
inhibit inducible nitric oxide synthase (iNOS) and measure outcomes including
measures of kidney function, metabolites and enzyme levels. Pending the results
from these experiments, the importance or non-importance of the arginine-
polyamine pathway to ADPKD will be confirmed or not, which is a critical decision
point for moving forward with our clinical program for DFMO in ADPKD.

## Key facts

- **NIH application ID:** 10080836
- **Project number:** 1R41DK125183-01A1
- **Recipient organization:** RESILIO THERAPEUTICS, LLC
- **Principal Investigator:** MICHAEL PETER VITEK
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,934
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080836

## Citation

> US National Institutes of Health, RePORTER application 10080836, DFMO Therapy for Polycystic Kidney Disease (1R41DK125183-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10080836. Licensed CC0.

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