# SUPPRESSION OF EROSIVE ARTHRITIS BY PROTEASE INHIBITORS

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1990 · $157,826

## Abstract

The project proposed will make use of recently discovered
antiarthritic agents of the amidine type to investigate the
pathogenesis of joint inflammation and to develop new avenues of
treatment.  A suitable proven experimental model is available in
the Lewis rat where a single systemic application of streptococcal
cell wall-derived peptidoglycan-polysaccharide fragments leads to
recurrent erosive polyarthritis.  The disease shares many features
with human rheumatoid arthritis the etiology of which is still
unknown and for which there exists no curative therapy.  Interest
in amidines arose when preliminary experimental studies showed
that BABIM (bis-(5-amidino-2-benzimidazolyl)methane) can block
completely the arthritic events.  Organic synthetic amidines of
the class proposed are highly potent inhibitors of trypsin and other
arginyl- or lysyl- directed estero-proteases.  Their beneficial
effect in inflammation is attributed to interference with the
action of humoral and/or cell-associated proteases.  The major
aims of this proposal are:  1) To establish in the arthritis model an
optimal dosing schedule for the pilot compound BABIM.  2) To
investigate in detail the influence of BABIM On the
histopathologic and immunopathologic parameters.  3) To test for
their therapeutic properties a series of additional promising
amidines and to try to correlate effectiveness with blockage of a
given enzyme.  4) To examine in vivo and in vitro whether the
anti-inflammatory properties of amidines are based on
interference with specific functions of macrophages and/or
neutrophilic polymorphonuclear leukocytes.  The results of the
planned in vivo and in vitro studies will provide deeper insight into
the etiologic factors involved in the arthritic process, the
mechanism of bone and joint destruction, and the cause of the
characteristic recurrences and remissions of the disease.  By
extrapolation, there will also be a clearer understanding of
arthritis in man, and there is great promise for obtaining an
effective agent for treatment of diseases such as rheumatoid
arthritis.

## Key facts

- **NIH application ID:** 3159500
- **Project number:** 5R01AR039460-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** J DIETER GERATZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $157,826
- **Award type:** 5
- **Project period:** 1988-07-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159500

## Citation

> US National Institutes of Health, RePORTER application 3159500, SUPPRESSION OF EROSIVE ARTHRITIS BY PROTEASE INHIBITORS (5R01AR039460-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159500. Licensed CC0.

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