A new therapeutic approach for brain repair in MS

Summary

MS is one of the most common, chronic neurologic diseases of adults worldwide, affecting over 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 to the US community of MS is just over $28 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 specific protein 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 scientists 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

Using a laboratory model of MS, Dr Petratos and his team showed that damaged areas of the spinal cord and optic nerve can be recovered. The team has been able to overcome the issues that promote nerve fibre damage by using a new haematopoietic (blood) stem cell delivery system to deliver a therapeutic molecule called Nogo receptor (1-310)-Fc fusion protein to MS disease areas only. This maximises repair of the brain where the myelin is damaged.

The team is now investigating this molecule as a treatment and its ability to repair MS-like brain stem cells as a proof-of-principle trial. It is anticipated that this investigation will translate use of the molecule and system towards a clinical treatment.

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.
Rashidbenam Z, Ozturk E, Pagnin M, Theotokis P, Grigoriadis N, Petratos S. How does Nogo receptor influence demyelination and remyelination in the context of multiple sclerosis? Front Cell Neurosci. 2023 Jun 8;17:1197492.doi: 10.3389/fncel.2023.1197492. eCollection 2023.
Ellen O, Ye S, Nheu D, Dass M, Pagnin M, Ozturk E, Theotokis P, Grigoriadis N, Petratos S. The Heterogeneous Multiple Sclerosis Lesion: How Can We Assess and Modify a Degenerating Lesion? Int J Mol Sci. 2023 Jul5;24(13):11112. doi: 10.3390/ijms241311112.
Dermitzakis I, Manthou ME, Meditskou S, Tremblay MÈ, Petratos S, Zoupi L, Boziki M, Kesidou E, Simeonidou C, Theotokis P. Origin and Emergence of Microglia in the CNS-An Interesting (Hi)story of an Eccentric Cell. Curr Issues Mol Biol. 2023 Mar 22;45(3):2609-2628. doi: 10.3390/cimb45030171.
Barmpagiannos K, Theotokis P, Petratos S, Pagnin M, Einstein O, Kesidou E, Boziki M, Artemiadis A, Bakirtzis C, Grigoriadis N. The Diversity of Astrocyte Activation during Multiple Sclerosis: Potential Cellular Targets for Novel Disease Modifying Therapeutics. Healthcare (Basel). 2023 May 29;11(11):1585. doi:10.3390/healthcare11111585.

Updated 31 March 2024

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