The project:

Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with high prevalence in Scotland. There are now effective drugs to prevent/alter inflammation and reduce relapses in MS, however we still have no treatments that effectively prevent neurodegeneration, which is the process that leads to accumulation of permanent disability. The goal of the MS Society Edinburgh Centre for MS Research, University of Edinburgh, is to find strategies and drugs that will protect nerves in MS, which can be moved to optimal clinical trials in MS.

Clinical trials to test drugs for progressive MS are difficult, as neurodegeneration and disability accumulate slowly and are difficult to measure objectively. Current trial imaging outcomes tend to rely on MRI measures of brain atrophy and myelin damage. Such structural imaging, however provides only limited specificity and sensitivity, and does not measure specific cellular and molecular changes of neurodegeneration, or indeed neuroprotection. PET scanning uses radioligands that are molecularly specific and provide sensitivity on a sub-nanomolar level. Synaptic vesicle glycoprotein (SV2A) PET ligands are being used to identify synaptic density in other diseases1. As cortical synaptic loss in MS occurs early2, we hypothesise that SV2A PET may be useful to identify relevant neurodegeneration early, and follow such a process over time.

The project will involve testing a new SV2A PET ligand called [18F]MNI11263 for measuring synaptic density on brain tissue sections in whole mouse brain with global (cuprizone) and focal1 cortical demyelination, and finally in vivo in the same mouse models. Neurodegeneration will be compared with and without repair/neuroprotection strategies, to understand the opportunities for detecting neuronal damage and the effects of targeted treatments in MS. Training opportunities include PET ligand chemistry, pre-clinical neuroimaging tissue immunofluorescence/microscopy/image analysis/pathology, in vivo mouse disease modelling, PET methodology and analysis, as well as engagement with people with MS and outreach through the MS Centre.

Please see the following for more information: https://www.edinburghneuroscience.ed.ac.uk/project/multiple-sclerosis-neurodegeneration/measuring-neurodegeneration-models-multiple-sclerosis

Contact: Prof Adam Waldman (adam.waldman@ed.ac.uk), MS imaging group (ms-imaging@ed.ac.uk)