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Identifying immune mechanisms in the CNS as targets for the treatment of paediatric Multiple Sclerosis (MS)


   School of Medicine, Dentistry & Biomedical Sciences

  Dr Y Dombrowski  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Paediatric MS accounts for 2.7-10.5% of the total MS population and can affect children of all ages. Paediatric MS is not curable and as such, is a lifelong debilitating disease that restricts the life quality of affected children for their entire life. MS over time becomes progressive and patients accumulate non-reversible disabilities. Thus, early intervention to delay progression and repair the damaged myelin tissue to retain neurological function for longer are key for paediatric patients. This project will determine if novel strategies to promote myelin repair by modulating immune mechanisms in the CNS can prevent neurodegeneration in paediatric MS. This could lead to novel therapeutics for MS treatment in the future.

The UK has the one of the highest rates of Multiple Sclerosis (MS) in the world. MS is mostly diagnosed in young adults between 20-40 years of age, but earlier onset in childhood can occur. This so-called paediatric MS accounts for 2.7-10.5% of the total MS population and can affect children of all ages. Paediatric MS is not curable and as such, is a lifelong debilitating disease that restricts the life quality of affected children for their entire life. MS over time becomes progressive and patients accumulate non-reversible disabilities. Thus, early intervention to delay progression and repair the damaged tissue to retain neurological function for longer are key for paediatric patients.

Paediatric MS differs from MS seen in adults by having a more inflammatory disease profile with more patients having cognitive deficits compared to adult MS patients who have more locomotive disabilities. Research into new treatments for MS is pre-dominantly geared at adult MS and no specific drugs or even clinical studies exist specifically for paediatric MS. Moreover, current paediatric MS patients receive the same treatment as adults yet 44% of paediatric patients have to switch treatment over a course of 3 years due to tolerance difficulties.

Recently, research strategies to promote repair of the damaged myelin sheath in MS have gained attention including in clinical trials for adults. Though no such therapies exist to date; however, they proof to have tremendous potential to repair myelin before neurodegeneration occurs and thereby preventing irreversible disability. Yet, we do not know if remyelination strategies could work for paediatric MS.

Modulating immune mechanisms that are present in inflammatory conditions to stimulate the myelin regenerative cascade could be a novel way to boost myelin repair. Inflammasomes are mediators of inflammation and are present in inflammatory MS lesions. Their role, however, is unclear.

Aims and Objectives

This PhD study aims to establish if remyelination could be a successful novel treatment strategy for paediatric MS, a disease for which no cure exists to date. Using a range of preclinical models of MS and human MS tissue, the PhD student will address the following objectives:

Objective 1: Characterising the profile of inflammasomes in paediatric vs adult human MS

Objective 2: Identifying the role of inflammasomes in myelin regeneration using preclinical paediatric MS models

Objective 3: Modulating inflammasome activity to promote myelin generation in a model of paediatric MS

The project is feasible to be delivered within 3 years. All experimental MS models are established, and clinical and research MS expertise is available in house, with additional support from established collaborations.

Start Date: October 2022


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