Project: Research project

Project Details


DESCRIPTION (Taken from the application):

Funding is requested to plan a phase II clinical study of arthritis gene
therapy. This study is an extension of a recently completed phase I clinical
trial in which the human interleukin-1 receptor antagonist (IL-1Ra) cDNA was
transferred to the metacarpophalangeal (MCP)joints of nine patients with
end-stage rheumatoid arthritis (RA). By an ex vivo strategy employing a
retrovirus (MFG-IRAP) and autologous synovial fibroblasts, it proved possible
to transfer the IL1Ra gene to rheumatoid joints and to express them within
those joints. No safety issues arose and all patients tolerated the procedure
well. In making the transition from the completed phase I, safety study to the
proposed phase II, efficacy study, it is necessary to make several
modifications to the protocol. These include the need to introduce the gene
into patients with earlier stage disease in order to determine any therapeutic
effect of the procedure. It is proposed to study patient in whom active disease
persists, despite having taken methotrexate for six months and Enbrel for three
months. In addition to evaluating the patients by standard American College of
Rheumatology criteria, the patients' joints will be assessed by magnetic
resonance imaging, plain radiography, and histopathological analysis of
synovial biopsies. Both knee joints and MCP joints will be used in the study.
Gene expression will be assessed by measurement of IL-1 Ra concentrations in
synovial fluid samples aspirated from knee joints. It is proposed to study ten
patients in this fashion. Each patient will be studied for six months, by which
time it will be possible to determine whether the gene treatment has had any
effect on inflammatory or erosive events within the treated joints. Safety
monitoring of the patients will continue annually for life, as required by the
Effective start/end date9/30/008/31/01


  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $127,125.00


  • Medicine(all)


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