Identification of biomarkers to improve the diagnosis and treatment of Multiple Sclerosis

Worldwide, 2.5 million of people are affected by multiple sclerosis, most commonly between 20 and 40 years old, with a prevalence among females. The lack of consensus over the causes of this disease is depicted by the presence in the literature of two antithetic visions about the multiple sclerosis etiopathogenesis. This has dramatic consequences on the clinical approach to the disease, which presently can be effective for a restricted percentage of patients, and on the market, currently ruled by immunomodulator drugs. This variability is one of the key points in the research of biomarkers for multiple sclerosis, and in this thesis, conducted at University of Huddersfield and at the Centre for Biomarker Research, two emerging targets are evaluated. The first one, the XBP1 gene, involved in endoplasmic reticulum stress response, codes two different isoforms that we evaluated through immunohistochemistry in post-mortem human brains of multiple sclerosis patients and healthy controls, in three areas: the frontal cortex, the basal ganglia and the temporal lobe. We found that the expression and the ratio of these isoforms are dysregulated between multiple sclerosis patients and controls. The second biomarker candidate investigated, instead, are the volatile organic compounds, collected via breath samples of multiple sclerosis participants and healthy controls. Unfortunately, due to the novel Coronavirus pandemic, the results of this study cannot be analysed further, but the methodology used in order to perform the breath tests was positively evaluated as non-invasive, providing an alternative for the diagnostic assessment of multiple sclerosis.