Monday, 7 January 2013

Research: Is a salt tablet going to treat MS make way for super saline

Mondal et al. Protection of tregs, suppression of Th1 and th17 cells, and amelioration of experimental allergic encephalomyelitis by a physically-modified saline. PLoS One. 2012;7(12):e51869. doi: 10.1371/ journal.pone.0051869. 

In multiple sclerosis (MS) and other autoimmune diseases, the autoreactive T cells overcome the resistance provided by the regulatory T cells (Tregs) due to a decrease in the number of Foxp3-expressing Tregs. Therefore, upregulation and/or maintenance of Tregs during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Here we have undertaken an innovative approach to upregulate Tregs and achieve immunomodulation. RNS60 is a 0.9% saline solution generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. RNS60, but not NS (normal saline), RNS10.3 (TCP-modified saline without excess oxygen) and PNS60 (saline containing excess oxygen without TCP modification), was found to upregulate Foxp3 and enrich Tregs in MBP-primed T cells. Moreover, RNS60, but not NS, RNS10.3 and PNS60, inhibited the production of nitric oxide (NO) and the expression of iNOS in MBP-primed splenocytes. Incubation of the cells with an NO donor abrogated the RNS60-mediated upregulation of Foxp3. These results suggest that RNS60 boosts Tregs via suppression of NO production. Consistent to the suppressive activity of Tregs towards autoreactive T cells, RNS60, but not NS, RNS10.3, or PNS60, suppressed the differentiation of Th17 and Th1 cells and shifted the balance towards a Th2 response. Finally, RNS60 treatment exhibited immunomodulation and ameliorated adoptive transfer of experimental allergic encephalomyelitis, an animal model of MS, via Tregs. These results describe a novel immunomodulatory property of RNS60 and suggest its exploration for therapeutic intervention in MS and other autoimmune disorders.

It is stated that it is suggested that in MS and other autoimmune diseases, the autoreactive T cells overcome the resistance provided by the regulatory T cells (Tregs) due to a decrease in the number of Foxp3-expressing Tregs (Really? Where's the proof?). Therefore boosting them will stop MS from developing. This is an approach being taken by many immunologists. Whilst this makes some sense as a mechanisms to limit potential autoreactivity, showing their activity on established CNS autoimmunity is relatively lacking, so as a therapeutic approach one would like to see more. 
In this study they they showed that normal saline (salt water at the salt concentration of the blood) did not do anything at 300 microlitre. This volume is above the UK recommended amount of volume for animal injections, which is 5ml/kg which means about 100 microlitre. We showed that with a bit more too also stops EAE. We assumed that it was stressing the mouses system and producing a stress response such as the production of steroids that are known to immunomodulatory.  

In this report they make a super saline under oxygen pressure which gives it a charge stabilized nano-structure and it takes on the ability to induce T reg cells and it can suppress EAE when administered at doses below 5ml/kg (see above). Is this the next new "cheap as chips" solution for MS, well it would have been good to see what happens when the wonder saline in given my mouth. Let us hope so. However, this is a product of a company, so it won't be cheap as chips.

There were no conflicts of interest standard deviations for that much for refereeing guidelines. But this work features heavily on a companies website. RNS60 can apparently treat models of Altzheimers and Parkinsons disease also, where not much T reg activity is known to be involved, but it is a neuropotective that works on voltage-gated ion channels and other voltage sensing proteins. They are talking clinical trials, why not see if it stops established relapsing disease and find if it works by mouth before trials..maybe this is done already.

1 comment:

  1. I'm certainly taking these results with a large pinch of salt!


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