|2016 Red Lab Coat Day celebrated by Steven Petratos & his group.|
L-R Erica Kim, Speros Thomas, Amani Alrehaili, Kylie Magee,
Melissa Beimond, Jae Young Lee, Steven Petratos
MS is commonly induced by the specific destruction of the protective sheath of nerve fibres, known as myelin. It has been shown in recent years that MS is a multifactorial disease with continual destruction of the nerve fibres even without large numbers of immune cells invading the brain and the spinal cord. Its classification as an ‘outside-in’, primary auto-immune disease, being based on symptoms rather than causes, is now being reconsidered as its mechanisms become better understood.
In addition to his role as senior lecturer and Education lead for CCS, Dr Steven Petratos is lab leader of the ‘Stem cell therapies for brain disorders’ group in the Department of Medicine. In late 2015 his research was awarded a $160,000 grant by Multiple Sclerosis Research Australia, a continuation of his recent international grant from the Progressive MS Alliance. Dr Petratos’ research is adding weight to the evolving ‘inside out’ hypothesis, that the original malfunction in MS takes place within the central nervous system (CNS), evoking inflammatory responses and neurodegeneration, governing permanent disability.
While the aetiology is still not fully understood, Dr Petratos’ research is identifying not only mechanisms which underlie neurodegeneration in MS but also means for combatting it. He has developed a specific technique using the ‘classic’ mouse model of MS. It involves the specific delivery of a therapeutic fusion protein, to limit deleterious axonal signalling during inflammation. It is introduced to bone marrow derived precursor cells by a lentivirus. When the precursor cells differentiate into adult immune cells, they go directly to where the disease is active. The therapeutic fusion protein can then act to block the production of a particular molecule - known as phosphorylated collapsin response mediator protein 2 (CRMP-2) - which accumulates in nerve fibres during MS activity and has a neurodegenerative effect.
Research by Dr Petratos, which was nominated in 2012 as best basic science paper in multiple sclerosis, showed that axons were preserved in the optic nerve during peak inflammation by inhibiting the phosphorylation of CRMP-2 in retinal neurons.
Dr Petratos is investigating a further novel strategy with the aid of MS Research Australia funding. The question he would like to answer is whether the signalling of a neuroreceptor known as NgR1 elicits axonal degeneration, and whether it is involved in immune-mediated demyelination and axon damage. He will use the stem cell based delivery system that his group has developed.
See more about the research at: www.med.monash.edu.au/medicine/alfred/research/petratos-group.html