Background
Many small molecules in the body are exquisitely sensitive to the presence of a disease. These molecules, which can include DNA, proteins, carbohydrates and fats, can be used as signatures to quickly and accurately detect a disease and to measure its progress or its response to a particular treatment. These “biomarkers” (short for biological markers) are found throughout the human body and can be measured by blood testing, tissue biopsies and advanced imaging techniques.
As multiple sclerosis (MS) manifests in a variety of different ways, there is a real need to gauge the disorder on a case-by-case basis – its type, aggressiveness and progression. In particular, identifying biomarkers for neurodegeneration – the process by which nerve cells and fibres become damaged and lead to irreversible disability – would be invaluable for monitoring disease progression and assessing responses to treatment. Biomarkers are perfectly suited to the task, as they provide a unique molecular signature with the potential to reflect how progressive MS evolves over time. To this end, a group of researchers including MS Society-funded postdoctoral fellow Dr. Erin MacMillan used an advanced diagnostic imaging technique to discover biomarkers of secondary progressive MS. Their findings were published in the Multiple Sclerosis Journal.
The Study
The authors used a non-invasive diagnostic imaging test, called magnetic resonance spectroscopy (MRS), to assess chemical changes in the brains of 46 participants with secondary progressive MS. MRS uses the same technology as magnetic resonance imaging (MRI). However, where MRI is set to generate anatomical images of the brain, MRS analyzes chemicals within the brain.
MRS scans were conducted once a year over a two-year period. The scans measured the concentrations of various molecules in a myelin-rich region of the brain. The researchers followed and compared concentrations of these molecules over the two-year period, looking for any changes over time. They also explored whether there was a correlation between concentrations of the molecules and participant brain size (assessed by MRI) and disability score (assessed using both the Expanded Disability Status Score and Multiple Sclerosis Functional Composite scale) over the two years.
Results
The concentrations of two molecules, glutamate and glutamine, decreased in the brain over the two-year period; glutamate fell an average of 4.2% per year, while glutamine fell an average of 7.3% per year as measured by MRS.
There was no change in disability score, and only a very minor decrease in brain size over time. There was no correlation between the participants’ brain size/disability scores and the fall in glutamate/glutamine concentrations.
Comment
The authors identified two brain molecules, glutamate and glutamine, as potential biomarkers for secondary progressive MS. Glutamate is a neurotransmitter; a type of chemical messenger that communicates signals between nerve cells. Glutamine is a by-product of glutamate that is collected and formed by supporting cells following the release of glutamate from nerve endings. The decline in the levels of these molecules, as noted by the authors, could mark continuing neurodegeneration in secondary progressive MS. Coupled with their high rate of decline year by year – much higher than either disability scores (none) or brain size (very minor) – the authors suggest that glutamate and glutamine offer a sensitive and specific measure of MS progression. This is a promising initial study and, as the authors conclude, with further research and validation, these biomarkers could one day be used in the clinic to monitor individuals with progressive MS and as an outcome measure to assess the response to a particular therapeutic.
Source
MacMillan EL et al. (2015). Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years. Multiple Sclerosis Journal. DOI: 10.1177.