# EFFECTS OF A POLYAMINE INHIBITOR ON MURINE LUPUS

> **NIH NIH R01** · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · 1990 · $161,884

## Abstract

The effects of in vivo inhibition of the biosynthesis of polyamines
on the clinical and immunopathological manifestations of murine
lupus will be studied using difluoromethylornithine (DFMO) in
three strains of autoimmune mice, male BXSB, female MRL-
1pr/1pr and female NZB/W.  DFMO is an irreversible inhibitor of
ornithine decarboxylase (ODC), a key enzyme involved in
polyamine biosynthesis.  The concentration of polyamines is
increased in systemic lupus erythematosus (SLE).  Preliminary
work suggests that polyamines may enhance the antigenicity of
DNA or increase the production of autoantibodies of both.  DFMO
treatment of a small group of MRL-lpr/lpr mice resulted in a
lowering of anti-DNA antibody levels and prolongation of life.
The possibility of a pathogenic role for polyamines in SLE will be
examined by:  (1) depleting the polyamine levels using DFMO and
studying the lifespan, clinical manifestations, and serum levels of
anti-DNA antibodies in DFMO-treated and untreated mice, and
(ii) immunizing normal mice, BALB/c with polyamines complexed
with polynucleotides and measuring the concentration of anti-
DNA antibodies in their serum.  The efficacy of DFMO in
combination with three drugs of known efficacy in murine lupus,
cyclosporin, corticosteroids and cyclophosphamide will be
determined.  To understand the effect of DFMO on tissue damage
characteristic of SLE, sections of kidneys, spleens, lymph nodes
and arteries of DFMO-treated and untreated mice will be
examined by light, immunofluorescent and electron microscopy.
The mechanism of action of DFMO will be studied by determining
changes in ODC activity and polyamine concentration in the
kidney and liver homogenates and plasma of DFMO-treated and
untreated mice and the functional status of spleen cells in these
animals.

The proposal represents a novel approach to understand the
pathogenesis of lupus and its treatment.  DFMO is a relatively
non-toxic drug.  If DFMO proves to be an efficient drug to treat
murine lupus, or combinations of DFMO and other drugs show
additive or synergistic effects, clinical studies to treat SLE
patients will be possible since considerable information on the
pharmacology and toxicity of DFMO is available from its use in
Phase I and Phase II studies on cancer patients.

## Key facts

- **NIH application ID:** 3159064
- **Project number:** 5R01AR039020-04
- **Recipient organization:** UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
- **Principal Investigator:** TJ THOMAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $161,884
- **Award type:** 5
- **Project period:** 1988-09-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159064

## Citation

> US National Institutes of Health, RePORTER application 3159064, EFFECTS OF A POLYAMINE INHIBITOR ON MURINE LUPUS (5R01AR039020-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159064. Licensed CC0.

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