Wednesday, 7 December 2011

MSers Ideas: Brains of Britain

Are Team G the Brains of Britain, well almost certainly not......although we do have our moments. We get inspiration from many places and sometimes this is for MSers asking us questions.


Dear Anon .....You recently asked a question about whether Team G had thought about alpha-Lipoic Acid (ALA) as a treatment for progressive MS..


We have looked at some fatty acids, although not ALA ,as potential treatments for progressive MS. As they are nutriceuticals/natural products, there is little commercial clout to get these types of study off the ground, and they must largely rely on charities/government to do these types of study.


We have had a look at the alpha lipoic acid and there is quite a literature on the action of lipoic acid in EAE. This has been reproduced in a number of independent labs in a number of different models. Those papers indicate that there is evidence for activity. The activity is claimed to be at the level of inhibition of white blood cell infiltration into the CNS. In human trials this would be easily seen by inhibition of gadolium enhancing lesions. There is no good evidence from this literature that the actions of the drug are not due to anything but immunosuppression. Any effect on nerves is secondary to an influence on the immune response preventing it arriving in the CNS. Therefore, there is no evidence that the drug is neuroprotective (no evidence it is not also). However if you go outside this literature and look at other non-autoimmune models of neurodegeneration, then there is evidence for neuroprotection and so this type of agent could give you a double whammy which you would want in progressive MS.


Although we could look at the nerve saving potential in animal models, given this extensive literature the value of repeating such a study is within the laws of diminishing returns . We would find it difficult to publish as the reviewers response would be what's new. Lack of originality is a good way to reject scientific publications.


The effective animal dose is about more than 50mg/kg which would be about 3-4g for humans. This is without the mouse metabolism factor, which normally increases the dose required for human activity about 12 times, because of the high metabolism of a mouse. However it is claimed that the 50mg/kg dose is actually equivalent to a 1.2g human dose, which is surprising but lets take that as read on face value.


However ,another reason for giving this a wide berth is that someone else is doing the work and they are apparently doing clinical studies (we can't do every thing). There has already been some preliminary work in MSers and you may be interested to know that there are two clinical trials that appear to be recruiting at the moment in Portland Oregon, USA


Lipoic Acid as a Treatment for Acute Optic Neuritis
ClinicalTrials.gov Identifier: NCT01294176
Estimated Enrollment: 54
Study Start Date: January 2011
Estimated Study Completion Date: March 2013


Lipoic Acid for Secondary Progressive Multiple Sclerosis (MS)
ClinicalTrials.gov Identifier: NCT01188811
Estimated Enrollment: 56
Study Start Date: October 2010
Estimated Study Completion Date: October 2015


However, the fact that other people are investing time and energy into to doing things you have found by your research shows that MSers can have great ideas too.


However, logic says let's see what these guys show. It would take us ages to get anything going even if we had the motivation to do it.. However I think with 56 participants, the study will be hopelessly underpowered (too few people to show a meaningful effect) such that if anything comes from this you may see a trend that will demand further studies. This is sort of why we need pharma on board to do studies that are powered to give a yes or no-go answer without wasting years doing little trials and repeating them.


Maybe one could think of mixing a nutricuetical with a pharmaceutical drug, but in the current climate pharma, is not receptive to this idea of multi-drug combinations. We are sure that in the future best practise will mean a cocktail of drugs.


The above post is an actual question posed........we thought, deliberated, researched and responded...it may be slow it may be quick and it may lead to new avenues of research for us.

5 comments:

  1. "There is no good evidence from this literature that the actions of the drug are not due to anything but immunosuppression."
    Hate to complain but this sentence is making my head spin and I can't understand what it says. Please rewrite without the double negative

    ReplyDelete
  2. Have you studied or heard anything on gamma linolenic acid. I believe it is used in diabetic neuropathy? Are peripheral nerves a completely different beast then the brain/spinal cord?

    ReplyDelete
  3. Dear Devin
    Yes, we have done some studies on n6 fatty acids of which linoleic acid is one as well as n3 also.

    There is a literature on actions of fatty acids and other oils

    There was a study in USA

    Placebo vs. Linoleic Acid Controlled Assessment of Treatment Efficacy in MS (PLACATE-MS)
    This study has been however terminated. The funding stopped due to slow enrollment in trial.

    So people were either not convinced to take option of a fat against activity of an established pharmaceutical drug or there was a sub text that the trial was not working so it was terminated.

    Hence my believe that there is a narrowing time window to do formal trials on these natrural products

    Because of ease of availability on these types of products it is easy for MSers to self-medicate from Health food shops (often owned by Pharma). Therefore as drug companies could not make money out of them so they won't pay to have the trials undertaken.

    This is the central prodlem with Natural products.

    ReplyDelete
  4. 1.http://www.ncbi.nlm.nih.gov/pubmed/6387534
    "Linoleic acid and multiple sclerosis: a reanalysis of three double-blind trials."

    2.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC493509/
    "Fatty acid composition of phospholipids from platelets and erythrocytes in multiple sclerosis"

    3.http://www.ncbi.nlm.nih.gov/pubmed/3588027
    "Red cell and hemorheological changes in multiple sclerosis."

    4.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC490958/
    "Rheological and fibrinolytic findings in multiple sclerosis."

    5.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC496015/
    "Platelet stickiness in multiple sclerosis."

    The concept: MSers have increased blood viscosity, that is the blood has greater internal friction that opposes to flow. This is due to decreased red cell elasticity (the red cells tend to aggregate into clusters more easily) and to increased platelet adhesiveness.
    Linoleic acid seems to reduce blood viscosity and has a beneficial effect on the severity and duration of relapses.

    Reduced blood viscosity is a well known feature of MS. Yet, there is no clear explanation as to why this happens, nor is there any investigation concerning the benefit of treating it, despite previous promising studies.

    Another aspect of MS that remains underexplored.

    ReplyDelete
  5. Correction: Increased blood viscosity is a well known feature of MS.

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.