Recombinant DMA Advisory Committee - 6/9-10/94 
revised Informed Consent document (as approved by the Institutional Review Board) 
incorporating the changes suggested by Drs. Haselkorn, Chase, and Zallen. 
IV-B. ANNOUNCEMENT OF FDA SPONSORED MEETING 
Dr. French Anderson of the University of Southern California, Los Angeles, California, 
announced that the FDA would be sponsoring an open meeting on "Production Issues for 
Human Gene Therapy" to be held immediately after the RAC meeting on June 9, 1994, 
in the adjacent conference room. The purpose of this meeting is to informally discuss 
issues surrounding the production of vectors for use in gene therapy protocols with FDA 
personnel. He said that this meeting would be the first of ongoing discussions between 
interested parties. This initial meeting is only to establish an agenda for future meetings. 
If there is sufficient interest, future meetings will be planned to coincide with RAC 
meetings. 
V. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: CLINICAL TRIAL TO ASSESS THE 
SAFETY, FEASIBILITY, AND EFFICACY OF TRANSFERRING A POTENTIALLY 
ANTI-ARTHRITIC CYTOKINE GENE TO HUMAN JOINTS WITH RHEUMATOID 
ARTHRITIS /DRS, EVANS AND ROBBINS 
RevieW“Dr. Parkman 
Dr. Walters called on Dr. Parkman to present his primary review of the protocol 
submitted by Drs. Chris Evans and Paul Robbins of the University of Pittsburgh, 
Pittsburgh, Pennsylvania. Dr. Parkman explained that there are two forms of interleukin- 
1 (IU-1), a, and p. lU-la causes symptomatology associated with infectious or 
inflammatory diseases, and attracts granulocytes to the site of inflammation. The body 
also produces a natural IL-1 receptor antagonist protein (ERAP) which neutralizes the 
effect of IL-1 a on its cellular receptors. So there is considerable research interest in 
attempts to reheve the IL-1 a symptomatology either by systemic administration of IRAP 
to patients or by administration of gene modified cells producing IRAP. Three areas of 
clinical or preclinical studies have been performed involving IRAP. The first area is the 
treatment of sepsis caused by gram negative bacteria or endotoxin shock syndrome. The 
results of these human trials have not been optimistic. The second area is prevention of 
graft-versus-host (GVH) disease. Animal studies have yielded optimistic results involving 
bone marrow transplantation. The third area is the treatment of chronic inflammatoiy 
diseases such as rheumatoid arthritis; these studies have been met with varying degrees 
of success. Most IRAP studies have been conducted by industry, and the data has not 
been published yet in peer-reviewed journals. 
The investigators have constructed an MFG-based retrovirus vector that encodes the 
genes for human IRAP and herpes simplex virus thymidine kinase (HSV-TK). The 
investigators propose to generate synovial fibroblasts from the knuckle joints of patients 
with rheumatoid arthritis who are scheduled to undergo surgery, transduce the fibroblasts 
with the IRAP vector, inject the transduced cells into the synovial space, and collect 
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