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Title: Imaging myelin basic protein expression in a model of remyelination by magnetic resonance imaging using an organic anion transporter protein gene reporter system
Author: Hill, Myfanwy
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2018
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Demyelination occurs in several CNS diseases. If demyelinated axons are not remyelinated they become vulnerable to irreversible degeneration. There is, therefore, a clinical need for therapies that enhance remyelination. This can be achieved by 1) pharmacologically targeting endogenous oligodendrocyte progenitor cells (OPCs) responsible for remyelination or 2) transplantation of myelinogenic cells (including OPCs). The first approach is appropriate for diseases with no defect in the myelinating cells, such as multiple sclerosis (MS), while the second approach is suitable for genetic disorders of myelination such as Pelizaeus Merzbacher disease (PMD). Translation into the clinic has or will shortly begin for both approaches. However, there are no current outcome measures providing direct evidence of OPCs differentiation to assess the efficacy of a remyelination therapy. This thesis presents data which it is hoped will form the foundation of a novel outcome measure for such therapies. It demonstrates that, by using a novel MRI gene reporter system; OATP, and controlling its expression under a Myelin Basic Protein promoter, OPCs can take up gadolinium based contrast, and be detected using T1 weighted MRI imaging in vitro and ex vivo. Using a constitutively active promoter, transplanted cells can be detected by an in vivo model of remyelination. It is hoped that this data will form the foundation for the development of an outcome measure for assessing the efficacy of new, pro-remyelination therapies, and provide a non- invasive, longitudinal, and translational imaging technique for use in drug discovery, or even personalised medicine.
Supervisor: Franklin, Robin ; Brindle, Kevin Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Myelin ; Oligodendrocyte Progenitor Cell ; OPC