Biomarker for transition to progression

Are the relapsing and progressive phases of MS truly different from each other? #MSResearch #MSBlog

“The following study uses a novel approach to differentiate MSers with different clinical forms of the disease, i.e. RRMS vs. SPMS vs. PPMS. The use a technique that profiles the metabolism of MSers and find that the metabolic profiles are different between the clinical sub-types. This is an exciting finding, but clearly needs to be reproduced in other cohorts of MSers.”

“The other issue is cause or effect. Could having progressive MS change your metabolism as a result of factors associated with progressive disease? For example, as a result of progressive MS  you are more likely to be less mobile and not exercise. In addition, progressive MSers are more likely to be constipated and as a result change their diets to manage the constipation. Being constipated changes your bowel flora that is part of your metabolism. Progressive MSers are more likely to have bladder dysfunction and hence dehydrate themselves to manage urinary symptoms. What does dehydration do to metabolism? Progressive MSers are older and more likely to have co-morbidities and hence take other medications for these, for example hypertension and diabetes. Hence, their are a lot of potential confounders that can affect the metabolism in progressive MSers; age being the main one.”

“What is interesting is that there a difference was found between SP and PP MSers? This may not be driven by factors I mentioned above and could relate to qualitative differences in the underlying mechanisms responsible for progression. This needs more work.”

“I have said many time that there is no magical point in time when MS becomes progressive. The mechanisms that underlie progressive MS are their from the outset and it is only when reserve capacity is exhausted in a particular neuronal system that progressive MS manifests itself. The systems that read out first are the ones with the longest axons, i.e. bladder and bowel. The length of the axons increases the likelihood of the pathway being hot multiple times and increases the chance of it running out of reserve capacity sooner. This is my so called asynchronous progressive MS hypothesis. In reality most people with MS are already in the progressive phase from the outset as manifest by accelerated and progressive brain volume loss. What is more important is can we switch off the processes underlying this and delay or prevent them ever manifesting with clinically progressive MS. I think we can as we now have a handful of therapies that impact on brain atrophy slowing it down and in some cases bringing the rate of brain volume loss to within a ‘normal range’. By preventing end-organ damage in MS we should maintain reserve capacity longer and at least delay, and possibly prevent, the clinical onset of SPMS.”

Epub: Dickens et al. A type 2 biomarker separates relapsing-remitting from secondary progressive multiple sclerosis. Neurology. 2014 Sep 24. pii: 10.1212/WNL.0000000000000905. 

OBJECTIVE: We tested whether it is possible to differentiate relapsing-remitting (RR) from secondary progressive (SP) disease stages in MSers using a combination of nuclear magnetic resonance (NMR) metabolomics and partial least squares discriminant analysis (PLS-DA) of biofluids, which makes no assumptions on the underlying mechanisms of disease.

METHODS: Serum samples were obtained from MSers with primary progressive MS (PPMS), SPMS, and RRMS; patients with other neurodegenerative conditions; and age-matched controls. Samples were analyzed by NMR and PLS-DA models were derived to separate disease groups.

RESULTS: The PLS-DA models for serum samples from MSers enabled reliable differentiation between RRMS and SPMS. This approach also identified significant differences between the metabolite profiles of each of the MS groups (PP, SP, and RR) and the healthy controls, as well as predicting disease group membership with high specificity and sensitivity.

CONCLUSIONS: NMR metabolomics analysis of serum is a sensitive and robust method for differentiating between different stages of MS, yielding diagnostic markers without a priori knowledge of disease pathogenesis. Critically, this study identified and validated a type II biomarker for the RR to SP transition in MSers. This approach may be of considerable benefit in categorizing MSers for treatment and as an outcome measure in future clinical trials.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that serum metabolite profiles accurately distinguish MSers with different subtypes and stages of MS.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


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