# ARTHRITIS:  INHERITED METABOLIC AND NUTRITIONAL CAUSES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1988 · $259,594

## Abstract

Among the many forms of arthritis a substantial portion shows a familial
aggregation, with some showing definite mendelian patterns of inheritance.
Included are some of the major causes of disability, yet only in the past
decade and a half has a start been made in the identification of specific
and biochemical abnormalities of metabolism that are responsible and in the
delineation of the specific mechanisms that lead to clinical expression of
arthritis.  The practical value of such an approach is well demonstrated in
the case of gouty arthritis.  A detailed understanding of the pathogenetic
mechanism responsible provided the basis for rational and effective
therapeutic intervention; consequently this disease is no longer a
significant cause of disability in this country.  In ochronotic arthritis,
where the primary genetic and enzyme defect producing alcaptonuria has been
well defined, the detailed molecular mechanism by which the accumulating
homogentisic acid produces the clinical symptoms of ochronotic arthritis in
adult life remains obscure.  Work on familial chondrocalcinosis, supported
by the grant, has shown an increased pyrophosphate content in cells
cultured from patients of a large kindred with this disease.  Both the
genetic and enzyme defect responsible for the increased pyrophosphate
concentration and the mechanism of pyrophosphate crystal formation in their
cartilage remains to be elucidated.

Specific objectives of the proposed research will be to identify additional
genetic and biochemical factors underlying the various types of heritable
arthritis, to determine the mechanism by which the biochemical lesion leads
to the pathological process and to devise more rational forms of
thereapeutic intervention by nutritional or pharmacological agents to
prevent the pathology.  Studies will first be made in vitro at the
molecular, biochemical and cellular level using fibroblasts and permanent
lymphoblast lines, as well as cultured chondrocytes from affected
patients.  Promising approaches in vitro will then be extended to clinical
studies of patients in vivo through the increased understanding of the
fundamental nature of the disorder.

## Key facts

- **NIH application ID:** 3154771
- **Project number:** 5R01AR013622-20
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** J E SEEGMILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $259,594
- **Award type:** 5
- **Project period:** 1979-05-01 → 1989-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154771

## Citation

> US National Institutes of Health, RePORTER application 3154771, ARTHRITIS:  INHERITED METABOLIC AND NUTRITIONAL CAUSES (5R01AR013622-20). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154771. Licensed CC0.

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