To overcome problems associated with conventional drug delivery in the treatment of rheumatoid arthritis (RA) our laboratory has been exploring the application of gene transfer as a means to express therapeutic proteins intraarticularly. Initial experiments in rabbit knee joints demonstrated that the gene encoding interleukin (IL)-1 receptor antagonist (IL-1RA) could be delivered to the synovial lining and expressed at a therapeutic level. The success of these experiments has led to the initiation of a clinical trial to assess the safety and efficacy of using gene therapy to treat RA. For this procedure autologous synoviocytes are retrovirally transduced in culture to express IL-1RA, and are transplanted into two metacarpophalangeal (MCP) joints of the hand. For comparative controls non-modified synoviocytes are injected into the remaining two MCP joints. During scheduled joint replacement surgery articular tissues and fluids are recovered and analyzed for expression of the IL-1RA transgene. Nine patients will be treated in groups of three; with each group receiving successively higher numbers of transduced synoviocytes. To date five patients have completed the procedure. Thus far it has been well tolerated and intraarticular expression of the IL- 1 transgene has been detected by both reverse transcriptase-polymerase chain reaction and in situ hybridization analyses. If this procedure indeed proves to be safe and feasible, future trials will address therapeutic efficacy and involve treatment in patients earlier in the progression of RA.
ASJC Scopus subject areas
- Pharmacology (medical)