Research: biomarkers and progressive MS

Epub: Jia et al. Development of protein biomarkers in cerebrospinal fluid for secondary progressive multiple sclerosis using selected reaction monitoring mass spectrometry (SRM-MS). Clin Proteomics. 2012;9(1):9. 

“The methods of this study will seem complicated to the uninitiated. Essentially we are using a method that separates out the proteins in spinal fluid using chromatography, which is a very old process; you may recall doing chromatography at school on ink solutions using blotting paper to separate out the different dyes. Once the proteins are separated we then use a very clever bit of kit to identify the proteins. We then collect the data and compare the groups using clever statistics to find out whether or not there are any differences between SPMSers and  other disease groups including healthy controls. We identified some proteins that were different that now need to be validated using other cohorts of MSers. The question is whether or not these results will hold-up! Let’s wait and see!”

BACKGROUND: MS is a chronic inflammatory disorder of the central nervous system
(CNS). It involves damage to the myelin sheath surrounding axons and to
the axons themselves. MS most often presents with a series of relapses
and remissions but then evolves over a variable period of time into a
slowly progressive form of neurological dysfunction termed secondary
progressive MS (SPMS). The reasons for this change in clinical
presentation are unclear. The absence of a diagnostic marker means that
there is a lag time of several years before the diagnosis of SPMS can be
established. At the same time, understanding the mechanisms that
underlie SPMS is critical to the development of rational therapies for
this untreatable stage of the disease.

METHODS: Using liquid chromatography (LC)
coupled mass spectrometry; we have established a highly specific and
sensitive multiplex selected reaction monitoring (SRM) assay. Our SRM
assay has facilitated the simultaneous detection of surrogate peptides
originating from 28 proteins present in cerebrospinal fluid (CSF).
Protein levels in CSF are generally ~200-fold lower than that in human
sera. A limit of detection (LOD) was determined to be as low as one
femtomole per uL. We processed and analysed CSF samples from a total of
22 SPMSers, 12 peopler with non-inflammatory neurological
disorders (NIND) and 10 age-matched healthy controls in parallel for the
levels of 28 selected potential protein biomarkers, followed by
principal component analysis (PCA) for clustering protein biomarkers. 

RESULTS: Our SRM data suggested different levels of agrin, kallikrein and
putative myosin-XVB in SPMS patients as compared to healthy controls.
PCA reveals that these proteins are correlated, can be grouped into four
principal components. Overall, we established an efficient platform to
verify protein biomarkers in CSF, which can be easily adapted to other
proteins of interest related to neurodegenerative diseases.

highly specific and sensitive multiplex SRM-MS assay was established
for verifying CSF protein biomarkers in SPMS. Three proteins were found
to be expressed significantly differently in SPMS patients as compared
to health controls, which may help further our current understanding of
SPMS disease pathology and/or therapeutic intervention.

A cartoon to demonstrate how liquid chromatography works.

“This collaboration was done as part of our Promise 2010 programme grant that was generously funded by the National MS Society and tthe MS Society of Great Britain and Northern Ireland – thank you.”

CoI: Members of Team G are authors of this manuscript

One thought on “Research: biomarkers and progressive MS”

  1. I see you just use ppms and nind and controls – but why not rrms patients? How do you know this test can identify progressive forms of the disease without comparing it to a relapsing form? I'm sure you did this but …..Whatever the outcome, agrin and kallikrein …. Never heard of them. Are they linked to ebv at all?

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