A novel approach to reduce the impact of progressive MS

Dr Steven Petratos

Monash University, VIC

| A cure via repair and regeneration | Neurobiology | Project | 2016 | Investigator Led Research |


The progressive phase of MS is thought to result from ongoing damage to the nerve fibre rather than the direct inflammatory attack on myelin. It is believed that destruction of the nerve fibres leads to permanent and increasing disability in progressive MS. Dr Petratos has been working on determining which molecules are responsible for this nerve fibre damage so that we can potentially stop it.

Using a laboratory model of MS, Dr Petratos’s group have identified a number of molecules that respond to the immune system damage, leading to a destructive cascade in the nerve fibres in the brain and spinal cord. If they can stop this cascade from being triggered they could potentially prevent the progressive damage in MS. In this project grant from MS Research Australia, fully supported by the Trish MS Research Foundation, Dr Petratos’ team will investigate a molecule known as NgR1 and attempt to block its activity in nerve cells. The blocking agent of NgRI will be delivered using a highly novel method that will allow accurate targeting of the NgR1 receptor.

Project Outcomes

Dr Petratos and his team are interested in specific molecules that are part of the molecular cascade that causes nerve fibre damage in MS. During this project, Dr Petratos demonstrated that one of the molecules, NgRI was key to nerve fibre damage and that damage was caused by NgRI interrupting molecular transport along the nerve fibres. By blocking NgRI, Dr Petratos showed that the transport of molecules along the nerve fibre was restored and that this reduced the amount of nerve fibre damage and symptoms seen in the MS-like illness in the mice.

The second part of this study involved the use of some highly novel and challenging techniques to allow the delivery of a therapeutic protein to sites of damage in a laboratory model of MS. This delivery system is based on immune cells in the blood and means that the therapeutic protein can work directly on the areas of damage. Dr Petratos and his team were able to demonstrate delivery of the therapy at the height of MS symptoms in a laboratory model of MS.  Excitingly, the therapy was able to reduce the symptoms of the MS-like disease and the nerve fibres were able to regrow and myelin damage was repaired.

It is hoped that if a similar system could be used in humans, it may be possible to limit the destruction which occurs to nerve fibres in the brain and spinal cord, giving a better clinical outcome for people with MS.

This grant has enabled the group to obtain funding from the Bethlehem Griffiths Research Foundation, submit three PhD, one Masters and two honours theses developing the next generation of MS researchers.


  • Bakhuraysah MM, Siatskas C, Petratos S. (2016) Is hematopoietic stem cell transplantation for multiple sclerosis a clinical reality? Stem Cell Research & Therapy 7(1):12.
  • Dahl LCM, Nasa Z, Chung JY, Niego B, Tarlac V, Ho H, Galle A, Petratos S, Lee JY, Alderuccio F, Medcalf RL (2016) The influence of differentially expressed tissue-type plasminogen activator in experimental autoimmune encephalomyelitis: Implications for multiple sclerosis. PLoS ONE 11(7):e0158653.
  • Lee JY & Petratos S (2016) Thyroid hormone signaling in oligodendrocytes: From extracellular transport to intracellular signal. Molecular Neurobiology 53(9):6568-6583. Tolcos M, Petratos S, Hirst JJ, Wong F, Spencer SJ, Azhan A, Emery B, Walker DW. (2017) Blocked, Delayed, or Obstructed: What Causes Poor White Matter Development in Intrauterine Growth Restricted Infants? Progress in Neurobiology 154:62-77
  • Lee JY, Li L, Velumian AA, Aui PM, Fehlings MG, McLean C, Petratos S. (2017) Nogo receptor 1 regulates axo-glial units in the central nervous system. Scientific Reports 7:8598.
  • Lee JY, Kim MJ, Deliyanti D, Azari MF, Rossello F, Stanley EG, Elefanty AG, Wilkinson-Berka JL, Petratos S. (2017) Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination. EBioMedicine 25:122-135.
  • Alrehaili AA, Lee JY, Bakhuraysah MM, Kim MJ, Aui P-M, Petratos S. Nogo receptor expression in Microglia/Macrophages during EAE progression. Neural Regeneration Research 2018
  • Mokhtar SH, Bakhuraysah MM, Aui P-M, Magee KA, Alrehaili AA, Steer DL, Kenny R, McLean C, Azari MF, Birpanagos A, Petratos S. (2018) The Amyloid-beta-dependent phosphorylation of CRMP-2 dissociates kinesin in Alzheimer’s disease. Neural Regeneration Research 2018
  • Lee JY, Kim MJ, Thomas S, Aui P-M, Harvey AR, Strittmatter SM, Petratos S. Targeting neuronal nogo receptor 1 (NgR1) signaling in experimental autoimmune encephalomyelitis (EAE) preserves axonal transport and limits demyelination. Acta Neuropathologica 2018 In preparation
  • Bakhuraysah MM, Lee JY, Alrehaili AA, Aui P-M, Kim MJ, Figgett WA, Mackay F, Siatskas C, Biemond M, Alderuccio F, Steven Petratos. BAFF stimulates Nogo receptor 3 expressing B cells prevalent at the induction of experimental autoimmune encephalomyelitis (EAE) prior to axonal damage and demyelination. Acta Neuropathologica 2018 In preparation
  • Kim MJ, Lee JY, Kang JH, Bakhuraysah MM, Alrehaili AA, Thomas S, Aui PM, Siatskas C, Alderuccio F, Biemond M Harvey AR, Strittmatter SM, Petratos S. Targeting neuronal nogo receptor 1 (NgR1) signaling in experimental autoimmune encephalomyelitis (EAE) preserves axonal transport and limits demyelination. Nature Medicine 2018 In preparation

Updated: 20 April 2018

Updated: 25 January, 2016



Grant Awarded

  • Project Grant

Total Funding

  • $160,000


  • 2 years over 2016 - 2017

Read More
Dr Litza Kiropoulos

Newsletter subscription

  • Enter your details

A novel approach to reduce the impact of progressive MS