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Measuring neurodegeneration in models of multiple sclerosis using positron emission tomography (PET)

   College of Medicine and Veterinary Medicine

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  Prof A Waldman, Dr A Tavares, Prof A Williams  No more applications being accepted  Funded PhD Project (Students Worldwide)

About 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.


This is one of two opportunities to carry out PhD research and join this mission in our centre. We are seeking students with an excellent undergraduate degree in a biological/neuroscience topic, with some research skills and much motivation and enthusiasm for our research

Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK. Applicants must ensure that they meet the eligibility requirements for postgraduate study at the University of Edinburgh.

There are no restrictions on nationality or residency. International applicants should pay particular attention to the English language requirements.

Funding Notes

This project will be funded by a studentship from the College of Medicine and Veterinary Medicine, University of Edinburgh. The studentship includes 3 years stipend at the standard UKRI rate, University of Edinburgh tuition fees, £5000 per year for 3 years for consumables and up to £500 per year for 3 years for travel and conference expenses.


1) Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Sci Transl Med. 2016 Jul 20;8(348):348ra96. doi: 10.1126/scitranslmed.aaf6667. PMID: 27440727.
2) Zoupi L, Booker SA, Eigel D, Werner C, Kind PC, Spires-Jones TL, Newland B, Williams AC. Selective vulnerability of inhibitory networks in multiple sclerosis. Acta Neuropathol. 2021 Mar;141(3):415-429. doi: 10.1007/s00401-020-02258-z. Epub 2021 Jan 15. PMID: 33449171; PMCID: PMC7882577.

3) Constantinescu CC, Tresse C, Zheng M, Gouasmat A, Carroll VM, Mistico L, Alagille D, Sandiego CM, Papin C, Marek K, Seibyl JP, Tamagnan GD, Barret O. Development and In Vivo Preclinical Imaging of Fluorine-18-Labeled Synaptic Vesicle Protein 2A (SV2A) PET Tracers. Mol Imaging Biol. 2019 Jun;21(3):509-518. doi: 10.1007/s11307-018-1260-5. PMID: 30084043.

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