Friday, 8 June 2012

Research Lipids and MS

Peggy PH, et al. Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation  Sci. Transl. Med. DOI: 10.1126/scitranslmed.3003831  Vol. 4, Issue 137, p. 137ra73

Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids’ saturated fatty acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as therapeutics for MS.

For many years people have focussed on proteins as targets for an immune response, but this group showed some time ago that lipids can also be targets for auto-antibody responses. But that was already known as antibodies against galactocerebroside (a lipid) could induce demyelination. 

In the past study it was reported that 
  • Lipid-array analysis (a technique to where different lipids=fats are stuck on slide and when a lipid -specific antibody is present it can be detected) showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis.  
  • Sulfatide-specific antibodies were also detected in SJL/J mice with acute experimental autoimmune encephalomyelitis (EAE).
  • Immunization of mice with sulfatide plus myelin peptide resulted in a more severe disease course of EAE, and administration of sulfatide-specific antibody exacerbated EAE. 
In this new study it was reported that 
  • Lipid-array analysis of (CSF) derived from individuals with multiple sclerosis showed that that antibodies targeted four lipids more often in MS patients than in the other groups. 
  • These four lipids were depleted at the sites where the nerve coatings were damaged-However the areas were demyelinated so no myelin, no myelin lipids (go figure) 
  • The four lipids — abbreviated as PGPC, azPC, azPC ester and POPS — share a similar phosphate (group of three oxygen molecules and a phosphorus molecule), to which the rogue antibodies bind. 
  • It is suggested that these these lipids are good lipids which act as brakes to immune function. Therefore the antibody response against them will stop the lipids from inhibiting the immune response and so cause damage when you do not produce enough of these lipids. 
  • They then supplement mice with MS-like disease with these lipids=fatty acids and there was some protection from the disease. 
This study suggests that some lipids inhibit the immune response and that autoimmunity to the lipids stop the inhibitory effect of the lipids. This group is now specialising in finding "brakes"..the immunological mechanics...only time will tell if this idea is a race car or a junker. 

On face value this suggests a new nutriceutical approach to treating autoimmunity, but before you start supplementing with lots of new fats, I would wait until there is evidence from clinical studies. I would also wait until someone independently repeats these studies. I say this because some of the neurological benefit reported was marginal and there appeared to be relapses in the treated groups and in my humble opinion the graphs sometimes told a different picture than the words, but best not say more or it will get me started. 

The study aimed to provide a translational approach by sticking fatty acids intravenously before disease starts. This is not very translational and nor is the route of administration, surely we need to see oral administration. However, we are making many of these fatty acids and putting them in the blood as we get older, as we clog up our arteries with atherosclerosis

We have been inducing EAE with whole tissue homogenate for years. Surely these are full of these fatty acids! So are the fatty acids really that immune inhibitory? 

We have yet another nutriceutical that can stop EAE, but be warned there are plenty of studies that show eating a tub of lard can stop EAE. However let us hope the group follow this up and show us that they have a new treatment for MS.

So to summarise using the car analogy the auto-antibody against fats can destroy fat-containing myelin,  like rust (antibody response) attacking the fabric of the car (myelin) so it gets destroyed (as shown in 2006). In this new study (2012) it suggests that the rust can remove the break pedal. This would cause a crash as you can not stop, so the car gets destroyed. Same result, but different routes to the problem.  However this latter study suggests a solution, supply more break pedals so rust is not that effective in inhibiting the car from crashing. So the car is usable for longer.


  1. Why is it anti-inflammatory to administer lipids that are autoantibody targets?

    Won't that cause more immune system response and more severe disease?

  2. In their studies they looked for antibodies against lipid=fats and found a load.

    So are the antibodies doing bad things or good things?

    In their original study that showed that the antibodies against sulphatide and sphinogmyelin were a bad thing and could make mouse MS worse. This fits with the idea that they are targets for destruction and part of autoimmunity..a bad thing.

    However in this new study they find antibodies against different fats occur and they believe that these fats are good fats that naturally stop autoimmunity (i.e. they are breaks), but because there are antibodies to the good fats which will block their function, then the effect is to remove goodness and this results in a bad effect also. Not because the fats are targets for damage but because they block the brake. So again a bad thing

    Therefore this implies a double whammy.

    Therefore in this context yes removing the break means there is more autoimmunity to cause more damage. Therefore they are suggesting supplementing the body with more brakes (fatty acids).

    So to summarise in the car analogy the auto antibody response can destroy the car like rust attacking the fabric of the car so it gets destroyd, or it can remove the break pedal and cause a crash so the car gets destroyed. Same result different routes to the problem.

    However one gives a solution

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  5. If anybody is interested this article has more information

  6. May be has more information, but where is the QC?

    "From wheelchair to a cane" is just plain mushroom food. It is from an attack to after an treated attac at best. It is very different from wheelchair to a cane. This is over hype.

  7. That's extreme overhype! esp after reading your take on it

    But the article is interesting and in simple enough language


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