Interleukin Therapy

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis affecting approximately 2.1 million Americans. It is a chronic, progressive, systemic autoimmune disease for which there is no cure.

However, over the last 10-15 years, biological therapies for immune dysfunction that occurs in RA have allowed doctors to treat patients more successfully ... in fact, often allowing the achievement of remission.

Gene therapy approaches have been used recently in the hope that patients who did not achieve remission can still get even need help.

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

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

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

Data from the initial phase I trial demonstrated that the injection into the joints tgAAC94 was safe and well tolerated in patients taking conventional disease modify anti-rheumatic drugs (DMARDs).

No drug-related serious adverse events were reported. beneficial results in that the signs and symptoms were also demonstrated.

Although this first study has demonstrated the safety and efficacy of gene therapy, a more recent study has confirmed.

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

"Arthritis is a good target for gene therapy () because the town is a confined space in which to inject genes," was a statement issued by Evans.

Unlike the study tgAAC94, the tissue was removed from the knuckle joints of two patients with severe RA and a harmless virus was inserted into the tissue cells to serve as a vehicle to carry a gene that blocks the action of interleukin-1 protein articulation. After being cultured to grow and multiply, the cells were reinjected into the affected joints.

One patient who received gene therapy in the two joints have experienced a 85 percent reduction in pain in a joint in one day, and both joints were pain-free from one week. Remarkably, the researchers report, joints receiving treatment were protected by the eruptions 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 document, therefore, also showed that pain symptoms can be alleviated by gene therapy.

These two studies have demonstrated that gene therapy is feasible in humans. More importantly, it has been shown that this approach may be useful for delivering biological agents in the joints rebels who do not respond to systemic therapies.