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):
- Axonal loss – neurofilaments
- Myelin loss – myelin basic protein
- Inflammmation – nitric oxide metabolites
- Glial/scarring activity – glial fibrillary acidic protein, S100B
- Repair and plasticity – neural cell adhesion molecule, GAP-43
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?
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.