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MS is an inflammatory disease which damages the myelin layer on nerve cells. This damage not only hinders the nerve impulses travelling down the nerve fibres, but also leaves the cells vulnerable to degeneration. It is thought that this nerve degeneration is a large contributor to progressive MS. Therefore, it is important that we discover ways to enhance the body’s natural abilities to regenerate its myelin layer (remyelinate nerve fibres). Dr Steven Petratos has been working on determining which molecules are responsible for nerve fibre damage, with the purpose of blocking the damage and protecting nerves.
Dr Petratos and his team have generated strong data indicating that a protein called MCT8 is vital for the survival of oligodendrocytes, the cells that are responsible for the creation of myelin. They have also developed a drug called DITPA, which can mimic the activity of the MCT8 protein. Their work so far suggests it may be possible to use this drug to enhance remyelination.
Scientists from Dr Petratos’ lab have shown that while myelin producing cells which lack MCT8 die, when they are treated with their DITPA drug, they survive and go on to mature into functional myelin producing cells. Additionally, in areas of MS disease activity in the human brain, there appears to be a reduction in the amount of MCT8 that can be found. This suggests that this is an important protein in the disease process.
This project sets out to conduct further laboratory tests of this potential new treatment for progressive MS, by investigating this drug as a way of repairing damage to the myelin protecting nerve cells. If successful, the team will ultimately aim to take the drug forward for testing in clinical trials in people with MS.
Dr Petratos and his team have examined the levels of the thyroid hormone transporter, MCT8, during mouse development and adulthood, and how it is affected in immune cells and oligodendrocytes (the cells that make myelin) in models of demyelination. He has also investigated the levels of MCT8 in human brain tissue with neurodegenerative disorders. Dr Petratos has shown that MCT8 levels are maintained in oligodendrocyte precursor cells (OPCs) throughout mouse development, suggesting it plays a role in their maintenance. Interestingly, its levels are substantially increased in immune cells and decreased in oligodendrocytes in the models of MS.
Dr Petratos has also shown that thyroid hormone signalling (a chemical system by which cells communicate with each other) is reduced in the models of demyelination and altered in human brain tissue with neurodegenerative disorders. While more analysis of these findings is required, they suggest that thyroid hormone transporters are necessary for cellular maintenance during mouse brain development, which is altered in adult demyelinating conditions. Dr Petratos is currently in the process of testing the drug, DITPA, in these models of demyelination. These findings may provide a new platform for investigation of novel interventions to limit further degeneration and promote remyelination in conditions such as progressive MS.
Dr Petratos has presented his research at national conferences and has received further funding from the Bethlehem Griffiths Research Foundation. He has also prepared and published several manuscripts in scientific journals.
Updated: 11 June 2020
$25,000
2019
1 year
Past project
