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GMSI Award 2015 – Molecular markers of multiple sclerosis disease progression

Gabriele de Luca

ECTRIMS_Ceremony_07_Gabriele_De_Luca

This lecture was given at the Grant for Multiple Sclerosis Innovation Awards Event, 8th October 2015. The GMSI award was supported by Merck KGaA, Darmstadt, Germany. Dr. de Luca is an award winner and works at the University of Oxford, UK.

Dr. de Luca explains in his talk that multiple sclerosis was unsurpassed in its variability and clinical outcomes. One of the greatest determinants of disease and disability was entry into the progressive phase. In most patients this was an unrelenting spinal cord syndrome with significant neuronal loss and axonal loss as a substrate for this disability.

The predominant genetic risk factor for multiple sclerosis was the HLA-DRB1*15 allele, which influenced the extent of spinal  cord disability. This was important for the presentation of antigens and could alter the phenotypic expression of this disease. In patients positive for this allele, the extent of demyelination was significantly greater, both within plaques and within normal white and grey matter.

In an attempt to understand these differences, Dr. de Luca and his colleagues planned detailed surveys of the proteome (the sum of all the proteins) and the metabolome (the sum of all small molecules) for CSF and spinal cord material from multiple sclerosis patients and controls. Cervical and lumbar cord samples would be compared for each case, with lesional and non-lesional samples for comparison. The top candidates would be examined and related to axonal loss, demyelination and progression.

Dr. de Luca considered that this should provide a unique opportunity to correlate quantitative SC neuropathology with proteomic and small molecule signatures. It could shed light on the pathogenesis of MS spinal cord pathology and therefore disease progression.

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