A new therapeutic approach for brain repair in MS

Dr Steven Petratos

Monash University

| A cure via repair and regeneration | Neurobiology | Project | 2022 | Investigator Led Research |
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Summary

MS is one of the most common, chronic neurologic diseases of adults worldwide, affecting more than 2.8 million people worldwide with 10,000 new diagnoses made each year. MS tends to strike early in adulthood, with women three times more likely than men to be diagnosed. The total direct cost of MS to the Australian community is over $2.4 billion annually.

MS is thought to be caused by the body’s own immune system mistakenly attacking the brain, spinal cord or optic nerves. The primary target of this attack is myelin, the protective coating around the nerve fibres, which carry nerve impulses between nerve cells. These attacks cause active MS lesions, and the nerve cells themselves can also be damaged leading to lifelong disability.

The research team, headed by Dr Steven Petratos, has shown that a modified version of a protein, called Nogo Receptor 1 (NgR1), is present within active MS lesions in a laboratory model of MS. This modified protein then interacts with another protein to cause nerve fibre damage. The researchers are now proposing a new method to block either the modification or the interaction between the two proteins, to halt disease progression and provide recovery from disability.

Progress to Date

Dr Petratos and his team have made great progress, successfully delivering a therapeutic protein to the sites of damage to the brain and spinal cord in laboratory models of MS. This can be quite difficult due to the blood brain barrier, a layer of cells that protects the brain and spinal cord, which tightly regulates and restricts molecules from entering. The team overcame this using immune cells of the blood to deliver the protein, which can infiltrate the blood brain barrier to reach lesions within the brain and spinal cord.

Delivery of this protein during peak symptoms in laboratory models of MS resulted in complete recovery from MS symptoms. Following recovery, the team found decreased nerve fibre degeneration and higher levels of small nerve fibres suggesting nerve fibre regeneration. They also observed less demyelination and an increase in remyelinated nerve fibres.

Dr Petratos and his team are now investigating the therapeutic protein’s ability to elicit repair of an MS-like brain generated from stem cells in a proof-of-principle trial.

This work has been published in several scientific journals, with the most recent paper also featured in the MS Wire in July 2023. Several more publications are in preparation.

This research could pave the way for innovative new treatments for progressive MS, addressing one of the largest unmet needs of people living with MS.

Publications

  • Ye S, Theotokis P, Lee JY, Kim MJ, Nheu D, Ellen O, Bedford T, Ramanujam P, Wright DK, McDonald SJ, Alrehaili A, Bakhuraysah M, Kang JH, Siatskas C, Tremblay CS, Curtis DJ, Grigoriadis N, Monif M, Strittmatter SM, Petratos S. Nogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model. Brain Commun. 2023 Apr 4;5(2):fcad108. doi: 10.1093/braincomms/fcad108. PMID: 37091588; PMCID: PMC10116608.
  • Nheu D, Ellen O, Ye S, Ozturk E, Pagnin M, Kertadjaja S, Theotokis P, Grigoriadis N, McLean C, Petratos S. (2022) Modulation of the Microglial Nogo-A/NgR Signaling Pathway as a Therapeutic Target for Multiple Sclerosis. Cells. 11(23):3768.

Updated: 17 July 2023

Updated: 14 February, 2022

Stages of the research process

Fundamental laboratory
Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline: 10+ years
Translational
Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline: 5+ years
Clinical Studies
and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline: 1-5 years

Investigator

Co-investigator

Grant Awarded

  • Project Grant

Total Funding

  • $225,000

Duration

  • 3 years

Funding Partner

  • Rotary Club of Moorabbin
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A new therapeutic approach for brain repair in MS