The recent death of a rheumatoid arthritis gene therapy study subject caused not only sorrow at the loss of life, but also concern regarding the future of gene therapy, at least in the minds of some.
For the time being, the company, Targeted Genetics Corporation of Seattle, has halted the study. The other 126 subjects are being evaluated.
But we should all be reminded that it is not yet clear if the death was directly related to the gene therapy. Also, there are a variety of different mechanisms by which gene therapy can be administered to a patient. And today I would like to discuss these, because, hopefully, tomorrow they will be one of the weapons that will be used against rheumatoid arthritis. Targeted gene therapy requires several things for it to become an effective and mainstream therapy.
Firstly, an adequate gene delivery approach is needed. Local injection is minimally invasive. Transgene protein leakage and the movement of treated joint lining cells can produce genetic responses at different sites. The efficacy of the distal effect can be variable. However, a more systemic approach might be more desirable, as rheumatoid arthritis is a systemic illness affecting multiple joints. The downside of this is that the increased dosages of the material carrying the gene which would be required for more systemic therapy may heighten the risk for side effects from that material and from the gene protein itself. Ideally, the future rheumatologist wants the ability to deliver the drug locally, but also having targeted spread to other areas of inflammation; or a systemic delivery system which focuses specifically to the areas of disease activity.
To accomplish what I just described, there are three approaches which can be used:
- Direct injection of the genetic material into the target tissue of the patient.
- Removing cells from the patient, treating them, and then injecting them back into the patient. This is superior to what I discussed above in item #1, in that a larger amount of cells could be reinjected, leading to longer-lasting expression of the transformed genes. This might avoid unnecessary activation of the patient's immune system. Unfortunately, this method of gene therapy is more labor intensive, and thus more expensive. It also is more invasive, requiring more procedures to harvest the cells from joint tissue, and implanting them again into the joint tissue.
- Using inflammatory cells as vehicles for gene therapy, as inflammatory cells migrate to the area of injury/damage/disease.
As you can see, there are many exciting things that are being explored for the betterment of the rheumatoid arthritis patient. And hopefully, they will all prove to be effective and safe. The initial word on that patient who died is that there was only trace amounts of the gene drug found in tissue outside of the injected joint. It appears that a fungus caused, at least directly, her death.
It remains to be seen how the approach to gene therapy goes forward.
Published On: October 02, 2007