29 May 2019

Spotlight on MS Research

Dr Steven Petratos and Dr Erica Kim
Thursday 30th May is World MS Day.  A global initiative to raise awareness for those affected by Multiple Sclerosis. This year's theme is My Invisible MS, an opportunity to make visible the symptoms of MS and educate the broader community. 

When Dr Erica Kim began her honours degree in the Neuroscience Department at Central Clinical School, she arrived with simply a passion for neuroscience. Now, with a PhD completed, along with two first author primary research papers, 2 author reviews and contributing author credits, it seems that this researcher is in it for the long haul with a firm focus on developing cell and gene-based therapies to treat intractable neurodegenerative disease, particularly Multiple Sclerosis.

Investigative research is a slow burn, particularly at a molecular level. It can take years to see a project translate from the investigative to pre-clinical stages and then there is no guarantee of progression to a clinical trial. Erica is keen to witness her earlier research progress into clinical trials. The molecules that have been the focus of her work, which may contribute or initiate such damage in MS are becoming known and by targeting them, it may be possible to limit the destruction, which occurs to nerve fibres in the brain and spinal cord, promoting a better clinical outcome for individuals living with MS.

In previous studies, the Neuroscience Department's lab led by Dr Steven Petratos, had discovered that limiting the signalling nogo receptor 1 (a protein, which in humans mediates axonal growth inhibition) in neurons, seemed to slow down the destruction of myelin (the protective sheath of nerve fibres that is attacked mistakenly by immune cells in individuals living with the degenerative disease) and importantly preserve the axonal integrity within the central nervous system. This lead to the question of how this could be applied at a pre-clinical level.

Dr Kim’s recent paper investigates further the role of nogo receptor 1 (ngr1) via three animal models targeting specific neurons. The paper reveals that by limiting neuronal nogo receptor 1 signalling in the optic nerve during experimental autoimmune-mediated demyelination, anterograde axonal transport is preserved and inflammatory demyelination abolished. The importance of this finding leads to the hypothesis that if we can achieve sustained communication in neurons of the central nervous system during an inflammatory attack, then we may be able to preserve neuronal cells and the myelin that ensheaths them from degeneration, thereby limiting the progression of MS.

The authors believe that the ability to differentiate between primary and secondary mechanisms of axonal degeneration may uncover therapeutic strategies to limit axonal damage and progressive MS.
This discovery has lead to the current pre-clinical therapeutic trial to antagonise nogo receptor within specific active inflammatory lesions of the central nervous system. This approach is utilising novel haematopoietic stem cell transplantation along with gene delivery technologies in pre-clinical models of MS. Future therapeutic adaptation of this technology for individuals living in progressive MS will be a huge boost at addressing this unmet medical need where currently modest therapeutic options exist. Protecting and repairing the damaged central nervous system is the major aim of this new study. The current funding support provided by Multiple Sclerosis Research Australia, Trish MS Research Foundation and the Bethlehem Griffiths Research Foundation, may assist the group in finding new avenues to translate their research into the clinic.

Jae Young Lee, Min Joung Kim, Speros Thomas, Viola Oorschot, Georg Ramm, Pei Mun Aui, Yuichi Sekine, Devy Deliyanti, Jennifer Wilkinson-Berka, Be'eri Niego, Alan R Harvey, Paschalis Theotokis, Catriona McLean, Stephen M Strittmatter and Steven Petratos Limiting neuronal nogo receptor 1 signaling during experimental autoimmune encephalomyelitis (EAE) preserves axonal transport and abrogates inflammatory demyelination Journal of Neuroscience 6 May 2019, 1760-18; DOI: https://doi.org/10.1523/JNEUROSCI.1760-18.2019

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