Sunday, 17 December 2017

A test for MS...Are we there yet?

Wow you said a new study that shows a simple test that can detect MS,

Hailing from “Gods own Country”,  I thought I would Investigate

The local Huddersfield rag (Newspaper) says

 “They have worked out how it can be detected using a simple blood test - up to now the only way to diagnose the disease has been through an invasive and often painful process of collecting fluid from the brain and spine”.

So already you know the newspaper is already talking rubbish and giving you visions of needles in the head. 

A lumbar puncture is not the typical diagnostic test these days and it is certainly not diagnostic as many conditions have oligoclonal bands. Importantly let’s not forget the good old magnetic resonance imaging machine for spotting those lesions. This is far more diagnostic.

Michael I. Page MI, McHugh P, Powles NT. Sphingosine and dihydrosphingosine as biomarkers for multiple sclerosis identified by metabolomic profiling using coupled UPLC-MS. Analytical Methods 2017.

The project aim was to identify differences in the metabolomic profiles in the serum of patients with multiple sclerosis (MS), those with neuropathic pain (NP) and those with both MS and NP compared with controls and to identify potential biomarkers of each disease state. Metabolomic profiling was performed using ultra-high-performance liquid chromatography coupled to mass spectrometry and the data analysis involved parametric methods, principal component analysis, and discriminating filter analysis to determine the differences between disease and control serum samples. Sphingosine and dihydrosphingosine were identified as significant biomarkers.



Apparently they found that "Sphingosine"  a lipid that makes spingosine-1 phosphate and "dihydrosphingosine" involved in ceramide production, which are Sphingolipids, are reduced in the blood. 

Version 2 20:18
In comparing Bloods from 30 people with MS verses 60 controls showed that Sphingosine levels were significantly lower in the multiple sclerosis groups compared with the control group giving p =  6.06 x 10*10. The control group had a mean peak area of 18, 990
±   6,286 (12,704-25,276). The multiple sclerosis groups had mean peak areas of 9, 535 ± 3,032 (6,503-12,567)for multiple sclerosis and 11 254 ± 3,863 (8,791-16, 117) for multiple sclerosis with neuropathic pain.

Similarly, the dihydrosphingosine levels were signicantly lower in the multiple sclerosis groups compared with the control group with p = 4.89 x  10*6 . The control group had a mean peak area of 7,723 ± 2,345, whereas the multiple sclerosis groups had mean peak areas of 4,936 ± 1, 389  for MS and 5,904 ± 1,581, respectively. Further studies will also need to be done with other controls.

It is therefore evident that there is not 100% specificity and 100% sensitivity to detect every one with MS and exclude people who don't have MS. Therefore, it will not be absolutely diagnostic. 

However, I would ask what are the biological processes that account for this? It is hard to think of anything that would be specific for multiple sclerosis as many of the pathological processes can occur in other conditions.

The Work is published in a local Newspaper on work from a Local University...So I doubt the breakthrough is really a breakthrough as it would be picked up by more media.

14 comments:

  1. Thanks MD. I think it is important to tackle these claims head on. Even at risk of displeasing colleagues. MS people need real hope. Not false promises of fools paradise.

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  2. https://www.researchgate.net/publication/320019200_Sphingosine_and_dihydrosphingosine_as_biomarkers_for_multiple_sclerosis_identified_by_metabolomic_profiling_using_coupled_UPLC-MS

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  3. Dont think you gonna like this.... :)

    "More than thirty years ago it was
    proposed that vitamin D deciency was a risk factor for MS and
    it has been shown that vitamin D has an immunomodulatory
    effect and sufficient levels can help protect against MS.7 Vitamin
    D promotes the production of regulatory T cells which
    suppresses the presentation of antigens to the T helper cells
    also reducing the activation and recruitment of these cells.8"

    They talk TTTT cells...

    Obrigado

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    Replies
    1. They talk TTT

      So do most people I'm afraid...

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    2. I use vitamin D3 plus Copaxone every day 10.400 IU of vitamin D3. At the time of the relapse that made me discover the disease my RV rate was very low.
      Then you'll know if it might be a diagnostic route, but probably not the only one.

      Delete
  4. Discussion
    Two compounds have been identied in this study as potential
    biomarkers for multiple sclerosis, sphingosine and dihydrosphingosine,
    which are found at signicantly lower
    concentrations in both the multiple sclerosis and the multiple
    sclerosis neuropathic pain groups. These sphingolipids have an
    eighteen carbon amino alcohol backbone and variations in this
    basic structure create a wide variety of sphingolipids that are
    utilised in constructing cell membranes and for acting as signalling
    molecules.24 Phosphorylation of sphingosine and dihydrosphingosene
    at the C1 hydroxyl group creates the important
    cellular signalling molecules sphingosine-1-phosphate and
    dihydrosphingosine-1-phosphate, respectively. Sphingosine is
    synthesised from the hydrolysis of sphingomyelin or from the
    precursors serine and palmitoyl-CoA.25
    Although a difference was anticipated between the neuropathic
    pain group and the multiple sclerosis/multiple sclerosis
    with neuropathic pain groups, with regards to levels of

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  5. sphingosine and dihydrosphingosine the neuropathic pain
    group showed a similar trend as the multiple sclerosis/MSNP
    groups indicating the possibility of underlying similar
    biochemical mechanisms in these three groups. Neuropathic
    pain can accompany multiple sclerosis as a result of demyelination
    but not all cases of multiple sclerosis include
    neuropathic pain.26
    Neuropathic pain without multiple sclerosis is a debilitating
    condition with limited treatment potential due to its unknown
    biochemical basis. Recently an LC-MS metabolomics study was
    carried out on rats which had been subjected to tibial-nerve
    transection (TNT). The results of this study showed alterations
    in sphingomyelin-ceramide metabolism. This was due to an
    increase in the levels of the enzyme sphingomyelinase which is
    responsible for catalysing the breakdown of sphingomyelin to
    ceramide and phosphoryl choline. In this study both sphingosine
    and dihydrosphingosine levels were elevated,27 in sharp
    contrast to the ndings reported here conducted on human
    samples with real disease conditions.
    Another study28 found differences in lipid composition in the
    white and grey matter of multiple sclerosis patients. Patients
    with active multiple sclerosis showed higher levels of phosphorylated
    sphingolipid but lower sphingolipid levels in both
    white and grey matter. This is in agreement with the results
    found herein from blood plasma analysis. In patients with
    inactive multiple sclerosis only white matter had increased
    phosphorylation of sphingolipids. One of these was phosphatidylcholine
    which on hydrolysis yields lysophosphatidylcholine29
    which can be used for the in vitro demyelination of nerve
    bres30 which could be another contributing factor to the
    progression of the disease.
    The drug ngolimod (2) has shown promise in clinical trials
    for the treatment of multiple sclerosis. Fingolimod is a sphingosine
    analogue which is phosphorylated in the body to form
    ngolimod-phosphate, this resembles sphingosine-1-
    phosphate (S1P). Currently ve S1P receptors have been
    discovered (S1P1–5) which are found on a variety range of cell
    types including lymphocytes and neural cells. The immune and
    central nervous system has a large number of S1P1–3 receptors,
    S1P4 receptors are usually found on lymphoid and hematopoietic
    tissue and S1P5 receptors are found on the white matter of
    the central nervous system. The S1P receptors in the CNS could
    contribute to the neuropathology of multiple sclerosis effecting
    neurogenesis as well as neural function and migration.31

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  6. Sphingolipids also play an important role in microbial
    pathogenesis regulating the balance between the microbe and
    the host. Most bacteria and viruses do not produce their own
    sphingolipids but instead use the sphingolipids of the host cell.
    The utilization of the host cells sphingolipids for the production
    of a microbial cellular membrane may be used by a microbe
    to hide from the immune system allowing colonisation. Alternatively
    the microbe may enzymatically functionalise the
    sphingolipid which may interfere with intracellular signalling
    thus avoiding removal and destruction from the host cell.32

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  7. May be there's a smell test for MS. It's in the news at the moment about a women that can smell Parkinson's disease.

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    Replies
    1. Yes it you look through the blog we have made posts on a guy from MIT who is developing this

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  8. Blood sample from the brain! My god what an awful lack of research from the beginning. Thats enough to put someone who thinks they may have MS off from persuing a diagnosis. I didn't need a LP, but was afraid i would. Glad this article wasn't out in the 4 years i suspected i had MS.
    Thank you for setting the record straight once again

    ReplyDelete

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