A proposal: How to study pro-myelinating proteins in MS

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the CNS. An unmet need in MS is repair i.e.,promoting endogenous regeneration and remyelination after demyelinating inflammatory injury. Remyelination is critical in neuronal preservation and the prevention of clinical progression. There is a good deal of evidence for histological repair and remyelination in MS patients. Repair is driven by several prominent endogenous pro-myelinating proteinsincluding neural cellular adhesion molecule (N-CAM) and brain derived neurotrophic factor (BDNF) among others. To follow changes during acute re-myelination in vivo in MS subjects, non conventional MRI techniques are necessary such as quantitative susceptibility mapping (QSM) that detects the release of Fe from dying oligodendroglial cells and myelin water imaging (MWI) that detects water captured within newly formed myelin. The best time to monitor changes in pro-myelinating proteins and link those changes to imaging evolution is immediately after the acute inflammatory response in MS lesions (gadolinium enhancement [Gd+]) during an intense period of remyelination. We can monitor MS subjects with new Gd + lesions with periodic imaging along with sampling of blood and CSF and determine if myelin formation is linked with increases in pro-myelinating proteins. This would lead to potential therapeutic manipulation with directly administered proteins to promote CNS re-myelination in animal models and in early clinical trials.