Institut de Recerca Vall d’Hebron, Spain: search of biomarkers
Search of biomarkers in patients with progressive multiple sclerosis
Principal Investigator: Xavier Montalban, M.D, Ph.D.
Institution: Institut de Recerca Vall d’Hebron (VHIR)
Amount Awarded: €74,250
Ending progressive MS is an urgent and unmet need that must be overcome so that people can live their lives without the uncertainty of what tomorrow will bring. Long-term follow-up of people with progressive MS is crucial to reducing this uncertainty and establishing a disease prognosis based on how the disease course evolves. This research team has followed a group of individuals with progressive MS for more than 10 years, and has carefully collected all the necessary clinical, radiological, and biological information to propose “biomarkers” that might be used as flags to predict individuals’ prognosis of progressive MS. Now they are using innovative technologies to mine this information for the identification of these predictive biomarkers.
What does this mean for people living with progressive MS?
It is crucial to have ways to predict an individual’s course of MS early on to help make rational treatment decisions. This project may not only reveal useful biomarkers, but also help to identify the molecular mechanisms that operate during progressive phases of MS and which might be blocked by therapies to stop progression.
This group aims to correlate variables with protein and mRNA biomarkers in the CSF (cerebral spinal fluid) and blood. In order to identify biomarkers associated with radiological and clinical variables, a CSF samples from 28 MS patients were evaluated. The CSF protein that was found to be most differentially expressed between patients with and without brain atrophy was LYVE1 (lymphatic vessel endothelial hyaluronan receptor 1), which is less abundant in the CSF of MS patients with higher brain atrophy. Interestingly, LYVE1 has been abundant in neurons of MS patients, and serum levels for these proteins were decreased in patients with progressive MS.
Regarding clinical progression, CSF levels of a neural cell adhesion molecule were decreased in patients with higher long-term disability progression, with depletion of this molecule proposed as one of the factors associated with disease progression in MS. In addition, the macrophage/ microglia biomarker CD163, proposed as a marker of neurodegeneration in MS, shows reduced CSF levels in patients with higher brain atrophy and higher long-term disability progression. Overall, they found higher levels of light and heavy chain immunoglobulins in the CSF of patients with higher brain atrophy and higher long-term disability progression, possibly indicating enhanced humoral immune responses in more aggressive patients.
To identify biomarkers in the peripheral blood cells, samples were obtained from 42 MS patients. mRNA screening was performed and the highest differential expression in patients with and without brain atrophy corresponded to the anti-apoptotic gene BAG3. This gene was upregulated in patients with higher brain atrophy. TOB1 was also found to be over expressed in patients with higher brain atrophy. Observations indicate that in patients with higher disability progression, there may be a possible role for pro-inflammatory genes in disease progression.
Principal Investigator: Xavier Montalban
Professor Montalban gained his medical license, trained as a Neurology specialist and completed his PhD in Neuroimmunology at the Universitat Autornoma de Barcelona. He then undertook a postdoctoral fellowship at the Lupus Research Institute, St.Thomas Hospital and additional clinical training at the National Hospital for Neurology and Neurosurgery, Queen Square in London, UK. He is Vice President of Fundació Esclerosi Múltiple (MS Foundation), Vice President of the Executive Committee of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS), and Vice President for Institutional Relations of the Spanish Neurological Society (SEN). He serves on the medical board and committee of the Multiple Sclerosis International Federation (MSIF), the European Charcot Foundation, and many other organizations, and is a committee member of the European Magnetic Resonance Research Group (MAGNIMS). He has authored over 200 publications, and recently directed the first Spanish (second worldwide) Multiple Sclerosis Clinical Practice Guidelines.
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