Gene therapy experiments are currently going to try and cure or alleviate arthritis pain. In the Science Daily article called Gene Therapy Demonstrates Benefit in Patients with Rheumatoid Arthritis looked at the possible outcomes in a positive gene transplant for arthritis patients. Gene therapy implants normal genes to counteract defected genes. The researchers found that “by implanting the gene at the affected joint, he was able to stimulate the interleukin-1 receptor antagonist to block stimulation of this cytokine.” Upon excising joint tissue, the researchers found less expression of the disease with less pain and symptoms. One must take in account that this therapy didn’t eliminate rheumatoid arthritis and other review articles show that arthritis is not caused by one cytokine. In the review article by Iain Mclnnes and Georg Schette on Cytokines in the Pathogenesis of Rheumatoid Arthritis, they found that the TNF cytokine may “crosstalk” with other cytokine complexes causing recognition and healing to be difficult to achieve. (pg. 439) Furthermore, due to the overwhelming number of types of arthritis, targeting the right cytokine is difficult.
Iain Mclnnes and Georg Schette, Cytokines in the Pathogenesis of Rheumatoid Arthritis. Nature publishing group 2007 www.nature.com/reviews/immunol
Do they actually implant the gene therapy to all affected joints? In my opinion I would say that this is really inconvenience, considering that gene therapy would only help to reduce the pain and symptoms of the rheumatoid arthritis. Let say if I had a rheumatoid arthritis in my hands that would mean they had to implant the gene in all the joints in my figures. The process also seems slow if I am on a real pain and I would like to reduce some of the pain immediately. I would also consider how often I would need to get the implant if it is just once or multiple times before getting it. So far I would rather use the regular medication in my opinion.
ReplyDeleteWhat's interesting about this treatment would be the mode of delivery. In the lab when we want to deliver/regulate a specific gene we typically use a virus with a plasmid that contains our gene of interest or something like an shRNA targeting our gene of interest for degradation. This type of delivery is a stable transfection, meaning the viral plasmid incorporates into the host DNA, much like a normal virus, and our plasmid will be propagated for a long time. We often have to use some kind of reagent to get that virus into our cells (but not all of the time). Yet in terms of humans, this type of delivery is not approved in the US so conceivably we could have the technology but not the approval.
ReplyDeleteSo where does this leave us? What other avenues can we investigate in the mean time? One interesting phenomenon is that some female patients (about 75%) with RA experience an amelioration of symptoms during pregnancy. While this process is poorly understood, what we know is that during pregnancy the maternal immune system has to adapt in order tolerate the growing fetus. So this might lead to a negative regulation, or reduction, of the maternal immune system, enough that it keeps the immune response seen in RA at a minimum. What would be interesting is taking what we learn about the mechanisms of pregnancy-induced amelioration of RA and apply that to a new treatment modality.
For more about immune tolerance in pregnancy, there is a post in this blog with that name. And for more about pregnancy-induced amelioration of RA here are a few papers:
http://rheumatology.oxfordjournals.org/content/early/2011/09/01/rheumatology.ker302.full
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709983/
Considering more than one cytokine is involved, it would probably be difficult to actually give patients some real pain relief by only eliminating one cytokine's functions. I guess maybe downregulating the entire immune system could offer some relief, but that isn't practical at all if patients all end up dying because of that. I wonder if there is some kind of antigen in the joints that the cytokines are detecting and inappropriately responding to? Maybe another form of gene therapy could be to change or eliminate the antigen shown on joint cells so that immune cells won't respond to them. However, then if they patient has an injury (like a broken bone or torn ligament) healing that would probably be much more difficult.
ReplyDeleteFor a short time, gene therapy was viewed as the future treatment for genetic disorders. By simply integrating genes into appropriate cells, based on the disease, almost any disease that has a known pathology could be treated. Either by upregulating genes or by upregulating proteins that could block over produced genes before they could cause an effect. The problem is regulation of the therapy. After several deaths linked to gene therapy, most notably Jesse Gelsinger, most researchers fell off the gene therapy band wagon. So, I think it is also important to look at the potential risks of such a treatment, the currently available treatments, and quality of life of people with the condition before we even concern ourselves with how effective they are. If we have a condition that although progressive, does not shorten lifespan drastically and the symptoms are fairly manageable with current treatments, it doesn't matter if the treatment cures everyone who undergoes it if half the people who have the treatment die. On the other hand, if a condition drastically shorten life or dropped quality life dramatically, then a 50:50 shot isn't so bad.
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