http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030338
Here is a link to the lay article number two covered previously in class. We discussed the possible benefits, if any, and the logic behind administering drug through the spine to modulate peripheral response. The article in itself didn't do much to describe the full process or techniques for which this type of experiment would be conducted, that is why I have attached a link for those that are interested.
In reading the full research experiment and carefully critiquing the process and thought behind doing such a test, a few positive benefits arise as well some side affects, which could possibly be detrimental. By administering the doses through the spine, a smaller dosage of treatment would be required to reach the desired effect, thus resulting in a saving of money and possible better distribution and targeting of the drug. But also we must understand that all these tests were conducted on rats and not human samples. Though there are many parallels between systems, there is no guarantee that the results will be the same. The goal which was desired was to see whether CNS is essential to achieve a response even when administered as a systemic treatment. Which in turn means that there would be a change in the way that drugs are manufactured, in hoping to get to the CNS quicker and easier, to achieve lower doses while improving efficacy.
After looking at the paper that the article was written about, many of the methods that they used to assess joint destruction seemed extremely subjective. Though they mentioned previous work indicating the importance of p38 MAP kinase and cytokines in RA, I was still a little unsure why they picked this as a target. Also, I am surprised that the same pathway would be present in both the joints and spinal cord. If p38 is a molecule that is involved in many different inflammation pathologies, it could have a significant effect on other areas of the body. It also seems that the benefits of a lower dosage gained by direct injection into the CNS could be outweighed by the danger of effecting the entire nervous system.
ReplyDeleteHowever, treatment through the CNS in place of systemic treatment seems to be a very innovative and novel approach with a great deal of potential. For this reason, I looked up a very recent paper in the BMC neuroscience called "Tri-partite complex for axonal transport drug delivery achieves pharmacological effect," which deals with direct CNS treatment. The molecule developed by Filler et al. has three parts: an axonal transport facilitator molecule, a polymer linker, and the therapeutic agent/drug. In this paper the researchers showed in mice studies that drugs targeted to specific sub-populations of neurons in the CNS could be very effective for treatment. Overall, I thought that this paper was very interesting because it showed that medication can be targeted to specific neurons, and effect only the desired area. The targeted CNS agents could potentially overcome the risks associated with systemic treatments and total CNS treatment. Here is a link to the paper: http://www.biomedcentral.com/1471-2202/11/8
That's actually a really good article in comparison to what we were looking at. Though initially it seems of benefit for total CNS treatment due to lower dose efficacy and cost effectiveness; but we were still unsure of the possible ensuing dangers that could come about due to that type of treatment. But targeting CNS agents could achieve the acquired goal while minimizing physiological risks
ReplyDelete