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Remyelination and neuroregenerative treatment

      Despite major progress in multiple sclerosis treatment, to date, accumulation of irreversible clinical disability is not sufficiently prevented with immuno-therapies. In this context, the clinical development of regenerative therapies is an urgent need. Large experimental evidence has been accumulated attesting that remyelinating demyelinated axons could prevent neurodegeneration. Many putative promyelinating drugs targeting oligodendroglial cells have now been identified, most of them being available for clinical trials. Manipulating the innate immune system could also result in enhanced remyelination extending the field of possible regenerative clinical trials. Finding the appropriate design to quantify remyelination in clinical trials is becoming an absolute prerequisite to allow the development of remyelinating therapies. Beyond neurophysiological measures such as evoked potentials, specific myelin imaging tools could overwhelmingly contribute to evaluate remyelination in vivo. Several MR-based sequences have shown promising sensitivity to myelin dynamics in MS, however their specificity for myelin is generally sub-optimal as they evaluate physical properties of tissues and not their biological content. Positron Emission Tomography (PET) with myelin specific tracers has the potential to specifically quantify myelin content in the brain. Compounds belonging to the stilbene and benzothiazole chemical classes have been shown to provide promising myelin radiotracers. Pilot trials have demonstrated that their application to MS in longitudinal studies enabled to monitor remyelination in white matter lesions and to stratify patients according to their endogenous remyelnation potential, opening the perspective to use PET combined with MRI in early phase trials.
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