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MS from preclinical findings to its lifetime course


Principal Investigator: Oluf Andersen

The preclinical course of multiple sclerosis extends asymptomatically over years, maybe decennia. Following onset (and diagnosis), the disease is to a varying degree active throughout life, although a minor proportion may escape a disabling progressive course. Available drugs are effective in the early relapsing-remitting phase but have a weak effect when started after the onset of a progressive phase. Prophylaxis is still not possible.

Extensive epidemiological and extensive register studies have convincingly defined environmental factors in the etiology of MS, including Epstein-Barr virus (EBV) infection. We approach the closely related issue whether EBV infection, particularly when manifested as infectious mononucleosis, leaves an activated state of the central nervous innate (activated microglia) and adaptive immune systems showing similarity or identity with MS trait (which we described), a preclinical state of MS. Thus, a possible rationale for prophylaxis (vaccination) against EBV-infection is evaluated. The question whether MS has become a milder disease (due to changes in environmental factors, diagnosis or therapy) is unsolved. Therefore, we develop prognostic models of MS severity, predicting risk of secondary progression, both long-term and continuously during the relapsing-remitting phase, based upon our 1950-54 Gothenburg MS cohort and the updated Swedish MS register. Long-term register data are used as historical controls for treatment of MS with first and second generation immunomodulatory drugs, including an age-related hazard function as outcome measure. We examine whether some MS courses are influenced by Mendelian (monogenic) genetics. We use two diseases with presumably simpler pathogenesis as human models for multiple sclerosis, the dominantly inheritable disease HDLS and the Guillain-Barré syndrome. Both of these disorders reveal issues concerning demylination and axon degeneration similar to MS.
 

Group members

Sara Haghighi, PhD, consultant in neurology

Daniel Jons, doctoral student, consultant in neurology

Helen Tedeholm, PhD, medical student

Bengt Skoog, PhD, senior consultant in neurology

Björn Runmarker, PhD, senior consultant in neurology

Christina Sundal, PhD, consultant in neurology
 

Page Manager: Katinka Almrén|Last update: 1/16/2019
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