Developing a novel drug for progressive MS

Our very generous supporters ‘dug deep’ at our 2018 Ball, enabling the Trish Foundation to fund an Incubator Grant awarded to Dr Steven Petratos.

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. The decreased levels of MCT8 in oligodendrocytes correlates with increased oligodendrocyte cell death during demyelination, which can be salvaged using DITPA.

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.

These findings suggest that thyroid hormone transporters are necessary for cellular maintenance during brain development in laboratory models, which is altered in demyelinating conditions. They also suggest that a reduction in thyroid hormone transport into oligodendrocytes may exist in demyelinating conditions such as MS. These findings will allow Dr Petratos to benchmark current remyelination therapies against DITPA to demonstrate its effectiveness in limiting further degeneration and promoting remyelination in conditions such as progressive MS.

This work has led to an international collaboration and patent application. 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.

Dr Petratos continues to make exceptional progress (please see the article on the Research Progress page of this website titled “Potential game-changer”) and in addition to funding from the Bethlehem Griffiths Research Foundation, he was awarded a three-year Trish Translational Research Grant, fully funded by the Trish Foundation commencing 2020.