| Rheumatoid arthritis (RA) is the most common form | | | | reported. Beneficial results as far as signs and |
| of inflammatory arthritis affecting approximately 2.1 | | | | symptoms were also demonstrated. |
| million Americans. It is a chronic, progressive, | | | | While this first study demonstrated both the safety |
| systemic, autoimmune disease for which there is no | | | | and efficacy of gene therapy, a more recent study |
| cure. | | | | confirmed it. |
| However, within the last 10-15 years, biologic | | | | Dr. Christopher H. Evans and co-investigators |
| therapies aimed at the immune dysfunction that | | | | reported their findings using a viral vector that carried |
| occurs in RA have enabled physicians to treat | | | | the gene that blocks interleukin-1, another protein |
| patients with much more success… in fact, | | | | that promotes inflammation and causes cartilage |
| often allowing the achievement of remission. | | | | breakdown, in the February issue of Human Gene |
| Gene therapy approaches have been employed | | | | Therapy. |
| recently in the hopes that patients who do not | | | | ”Arthritis is a good target for (gene therapy) |
| achieve remission may still yet get needed relief. | | | | because the joint is a closed space into which we |
| The first gene therapy approach was developed by | | | | can inject genes,” was a statement issued by |
| Targeted Genetics in Seattle, Washington. Their | | | | Evans. |
| compound, tgAAC94 was developed as a potential | | | | Unlike the tgAAC94 study, tissue was removed from |
| supplement to systemic anti-TNF-alpha (anti-tumor | | | | the knuckle joints of two patients with severe RA |
| necrosis factors drugs such as Enbrel, Humira, and | | | | and a harmless virus was inserted into the tissue |
| Remicade have become the standard of care for | | | | cells, in order to serve as a vector to carry a gene |
| rheumatoid arthritis) therapy for use in patients with | | | | that blocks action of the interleukin-1 protein to the |
| inflammatory arthritis who had one or more joints | | | | joint. After being placed in culture to grow and |
| that did not respond to systemic therapy. | | | | multiply, the cells were injected back into the afflicted |
| The product used a recombinant adeno-associated | | | | joints. |
| virus to deliver a DNA sequence that coded for a | | | | One patient who received gene therapy in two joints |
| form of the TNF-alpha receptor (TNFR). TNFR blocks | | | | experienced an 85 percent reduction in pain in one |
| the immune stimulating activity of TNF-alpha. Direct | | | | joint within 1 day, and both joints were pain-free |
| injection of tgAAC94 into affected joints leads to | | | | from 1 week onward. Remarkably, the researchers |
| the localized production of soluble TNFR within joint | | | | report, joints receiving the therapy were protected |
| cells, reducing the activity of TNF-alpha within the | | | | from flares that occurred during the study period. |
| joint and, potentially, leading to a decrease in the | | | | The second patient also responded to gene therapy, |
| signs and symptoms of disease and stopping joint | | | | with a 70 percent reduction in pain between weeks 2 |
| destruction. | | | | and 3. |
| The adeno-associated virus is a naturally occurring | | | | This paper, therefore, also showed that painful |
| virus that has not been associated with any disease | | | | symptoms can be lessened through gene therapy. |
| in humans. | | | | Both of these studies have demonstrated that gene |
| Data from an initial Phase I trial demonstrated that | | | | therapy is feasible in humans. More importantly, it has |
| injecting tgAAC94 into joints was safe and | | | | been shown that this approach may be helpful for |
| well-tolerated in patients taking conventional disease | | | | delivering biologic agents into stubborn joints that do |
| modifying anti-rheumatic drugs (DMARDS). | | | | not respond to systemic therapies. |
| No drug-related serious adverse events were | | | | |