However, within the last 10-15 years, biologic therapies aimed at the immune dysfunction that occurs in RA have enabled physicians to treat patients with much more success… in fact, often allowing the achievement of remission.

Gene therapy approaches have been employed recently in the hopes that patients who do not achieve remission may still yet get needed relief.

The first gene therapy approach was developed by Targeted Genetics in Seattle, Washington. Their compound, tgAAC94 was developed as a potential supplement to systemic anti-TNF-alpha (anti-tumor necrosis factors drugs such as Enbrel, Humira, and Remicade have become the standard of care for rheumatoid arthritis) therapy for use in patients with inflammatory arthritis who had one or more joints that did not respond to systemic therapy.

The product used a recombinant adeno-associated virus to deliver a DNA sequence that coded for a form of the TNF-alpha receptor (TNFR). TNFR blocks the immune stimulating activity of TNF-alpha. Direct injection of tgAAC94 into affected joints leads to the localized production of soluble TNFR within joint cells, reducing the activity of TNF-alpha within the joint and, potentially, leading to a decrease in the signs and symptoms of disease and stopping joint destruction.

The adeno-associated virus is a naturally occurring virus that has not been associated with any disease in humans.

Data from an initial Phase I trial demonstrated that injecting tgAAC94 into joints was safe and well-tolerated in patients taking conventional disease modifying anti-rheumatic drugs (DMARDS).

No drug-related serious adverse events were reported. Beneficial results as far as signs and symptoms were also demonstrated.

While this first study demonstrated both the safety and efficacy of gene therapy, a more recent study confirmed it.

Dr. Christopher H. Evans and co-investigators reported their findings using a viral vector that carried the gene that blocks interleukin-1, another protein that promotes inflammation and causes cartilage breakdown, in the February issue of Human Gene Therapy.

“Arthritis is a good target for (gene therapy) because the joint is a closed space into which we can inject genes,” was a statement issued by Evans.

Unlike the tgAAC94 study, tissue was removed from the knuckle joints of two patients with severe RA and a harmless virus was inserted into the tissue cells, in order to serve as a vector to carry a gene that blocks action of the interleukin-1 protein to the joint. After being placed in culture to grow and multiply, the cells were injected back into the afflicted joints.

One patient who received gene therapy in two joints experienced an 85 percent reduction in pain in one joint within 1 day, and both joints were pain-free from 1 week onward. Remarkably, the researchers report, joints receiving the therapy were protected from flares that occurred during the study period.

The second patient also responded to gene therapy, with a 70 percent reduction in pain between weeks 2 and 3.

This paper, therefore, also showed that painful symptoms can be lessened through gene therapy.

Both of these studies have demonstrated that gene therapy is feasible in humans. More importantly, it has been shown that this approach may be helpful for delivering biologic agents into stubborn joints that do not respond to systemic therapies.