Sunday, 29 March 2015

My biomarker wishlist for the MS-SMART study

Those of you I met and talked to at the 'MS Research Day' on the 21.3.2015 would already know that my field of work is on biomarkers - specifically biological markers found in bodily fluids.

A biomarker is "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention" (NIH Biomarkers Definitions Working Group definition). For example, blood pressure is a marker of a biological process, cholesterol is a marker of a pathogenic process i.e. heart disease, and CA-125 (as Angelina Jolie-Pitt is in the news for having this measured!) is a marker of ovarian cancer treatment response.

It is apparent that in the time-frame of a progressive MS trial two years is too short to see a true clinical benefit. Why is this you might ask? Well...realistically speaking if you look back at how long it took for you to develop the disability, you're probably looking at a treatment strategy which targets long-term stabilisation, with no apparent physically/clinically evident changes in the short-term.

This is, however, not to say that changes are not taking place in your body, they are....and this is at the level of your brain cells. Changes in this can be visualised by MRI brain atrophy measures but can also sampled in the spinal fluid; which is my area of interest. My plan is to devise a biomarker strategy for MS-SMART that looks at the changes that are modulated by the trial drugs (fluoxetine, riluzole, amiloride) in the body, as well as those which are suggestive of a good clinical outcome i.e. a positive treatment effect (see Figure below).





Figure: Diagrammatic representation of my biomarker strategy. Therapeutics 1-5 all have different modes of action and the stem biomarkers are representative of this, whilst the biomarker at the trunk is more representative of the desired clinical outcome (in this case reducing disability).

I plan to look at the following (biomarkers listed):
I am interested to know what you think? Have you heard of a biological marker which would be interesting to look at, or are interested in finding out more on a specific process in progressive MS? 

Please write in the comments section below.

MSers participating in the MS-SMART trial are participating in this study on a voluntary basis, and so far 13 MSers have consented. Thank you.

7 comments:

  1. Very interesting and meaninful area of research NeuroDoc

    I haven't heard about anything besides neurofilaments, unfortunately but good luck nonetheless.

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  2. Thanks. Others haven't been as well publicized but worth their weight in gold. The regenerative biological markers were my doctorate, the hypothesis is that progression in MS may be related to lack of neuroplasticity than simply neurodegeneration!

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  3. Very interesting - I am enjoying your additions to the blog Neuro Doc :) How are these biomarkers measured - do they require participants to undergo an LP? Is there anyway of measuring them from a simple blood test?

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    1. Yes, LPs and blood based on sites best for their measurement. GAP-43 which is a marker of axonal elongation and synaptogenesis (how memory is formed) is only found in the CSF.

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  4. Good luck to you and the team. This research is much needed, hope you find something that can be useful very soon

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  5. neuronal mitochondrial integrity : NAA (N-acetylaspartate)

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    1. Thanks Steve, NAA is also being measured using MRI spectroscopy as exploratory work in this trial.

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