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The drug fingolimod (also known as Gilenya or FTY-720) is believed to exert its effects principally by reducing the number of inflammatory immune cells that can be released into the circulation. However, some of the molecules involved in this chain of events are also found in the brain and spinal cord. This raises the question as to whether fingolimod acts directly on the central nervous system and, importantly, whether this interaction could be neuroprotective.
The aim of this project is to generate an experimental system to address this question. Specifically, the project will determine whether nerve cells grown in the laboratory produce the molecules required to respond to fingolimod. If successful, these cells will provide a laboratory model for testing the action of fingolimod in later studies.
This project is now completed and Tao has successfully produced a laboratory model for the testing of a response to fingolimod. Tao tested whether molecules required to respond to fingolimod were present in two types of neuronal cells grown in the laboratory from mice and one neuronal cell type derived from humans. Tao looked at three molecules, known as S1P-R1, S1P-R3 and S1P-R5 under his experimental system. He showed that all three molecules were present in all cell types, implying that there may be a neuroprotective effect of fingolimod that acts through these molecules. This work also showed that the S1P-R1 molecule had an unusual and unexpected pattern of expression within these neurons.
Further work, using neurons recovered from the laboratory model of MS, experimental autoimmune encephalomyelitis, showed that fingolimod reduced the level of these molecules within the system when compared with no treatment. The levels of the molecules in the neuronal cells grown in the laboratory are now being tested.
Updated: 1 July 2013
Tao Nelson
Dr Jacqueline Orian
$7,000
2013
1 year
Past project
