Clinical trials in the gene therapy of arthritis

Gene therapy clinical trials raise important safety issues that complicate their design and require extensive preclinical testing, Human protocols for the treatment of arthritis and most other orthopaedic and rheumatologic in dications are complicated additionally by the perception that they are larg ely acquired, nonlethal conditions, Taking these considerations into accoun t, the first such human study used the local, ex vivo delivery of a gene wh ose product, the interleukin-1 receptor antagonist, has an outstanding safe ty profile. This gene was delivered to the metacarpophalangeal joints of po stmenopausal women 1 week before these joints were removed during total joi nt replacement surgery, In addition to providing an additional safety cushi on, the surgical removal of the genetically modified joints made available large amounts of tissue to examine for evidence of successful gene transfer and gene expression, This Phase I safety study was approved at the local a nd federal levels, and its funding was contingent on the establishment of a n external monitoring board, This trial now has been completed and a Phase II, efficacy study is being planned. A similar study has begun in Dusseldor f, Germany and results from the first two patients are similar to the resul ts of the American patients. Permission has been given for two additional h uman trials, one in the United States and one in the Netherlands, in which a gene encoding herpes thymidine kinase will be transferred to the joints o f patients with rheumatoid arthritis who then will be administered gancyclo vir, This procedure aims to treat the disease by producing a genetic synove ctomy, Additional development of human gene therapies for arthritis and oth er orthopaedic and rheumatic conditions will be aided by the successful com pletion of these studies.