MOG antibody: a biomarker to prevent blindness - MS Research Australia

MOG antibody: a biomarker to prevent blindness

Dr Fabienne Brilot-Turville

University of Sydney and the Children’s Hospital at Westmead, NSW

| Better treatments | Immunology | Project | 2015 | Investigator Led Research |
SUPPORT PROJECTS WITH THIS RESEARCH FOCUS

Summary

A characteristic of MS is demyelination, or loss of myelin around the nerve cells of the brain and spinal cord. Demyelination often also occurs around the optic nerve in people with MS, resulting in vision problems. Recurrent attacks of inflammation on or around the optic nerve can lead to blindness.

Dr Fabienne Brilot-Turville and Associate Professor Dale have recently found an antibody in the blood of children and adults with optic neuritis (inflammation of the optic nerve). This antibody attacks a protein called myelin oligodendrocyte glycoprotein (MOG), an important protein on the insulation layer of the optic nerve. They have shown that this MOG antibody can lead to damage of the insulation on the optic nerve.

Dr Brilot-Turville’s study is a nationwide study of children and adults with optic neuritis at a high risk of blindness. From the blood of these people, Dr Brilot-Turville’s team will identify children and adults with the MOG antibody. She will also explore how this antibody is involved in optic neuritis.

The detection of MOG antibody will help us to provide a better treatment to reduce the attacks, and therefore save the vision of these patients.

Project Outcomes

Optic neuritis or inflammation of the optic nerve is a common feature of MS. However, not everyone who has optic neuritis will go on to develop MS. Dr Brilot-Turville is investigating whether the presence of MOG (myelin oligodendrocyte glycoprotein) antibodies in the blood can be used to diagnose whether patients has optic neuritis or MS associated optic neuritis. Her team has discovered that around half of people with the MOG antibody have optic neuritis, and the other half have a range of other neurological conditions or diseases.

To date, Dr Brilot-Turville has collected blood from a number of patients and has been following their clinical symptoms. Results so far suggest that MOG antibodies are rare in patients with MS associated optic neuritis, and were more common in other demyelinating diseases.

Additionally, Dr Brilot-Turville is examining the levels of MOG antibodies in the blood of patients currently undergoing immunotherapies. Dr Brilot-Turville has amassed the largest collection of samples in the world to undertake this and it is hoped the MOG antibody levels may be able to predict whether the therapy is being successful or not before any potential relapses. This would allow clinicians to modify treatment regimens before further relapses happen, hopefully leading to more successful disease management. Findings so far indicate that more than half of people that have MOG antibodies are likely to develop further and sustained disabilities, most of these people however, would benefit from steroid treatments.

This grant has also helped this team establish the Brain Autoantibody Testing Referral Centre to provide MOG antibody testing for the whole Asia Pacific region. The Centre is currently providing MOG antibody tests for 1800 patients per year.

Dr Brilot-Turville’s team are also investigating the physical interaction between MOG and the antibodies that bind to MOG. This is important to ensure that slight chemical changes in the protein don’t prevent this binding and therefore give any potential clinical tests false results. They have discovered a range of slight chemical modifications that may prevent the detection of MOG, and thus these will need to be overcome for this can become a useful commercial diagnostic test.

During this grant, Dr Brilot-Turville and her team have presented their work at national and international conferences, meetings and presentations to the general community.

Dr Brilot-Turville’s work hopefully will help bring MOG antibody testing into routine clinical practice leading to better disease diagnosis and management.

Publications

  • Sinmaz N, Nguyen T, Tea F, Dale RC, and Brilot F, Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system. J Neuroinflammation, 2016 Aug 30;13(1):219.
  • Ramanathan S, Dale RC, Brilot F. Anti-MOG antibody: the history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev. 2016 Apr;15(4):307-24
  • Kothur K, Wienholt L, Tantsis EM, Earl J, Bandodkar S, Prelog K, Tea F, Ramanathan S, Brilot F, Dale RC B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination. PLoS One. 2016 Feb 26;11(2):e0149411.
  • Ramanathan S, Prelog K, Barnes E, Tantsis E, Reddel SW, Henderson A, Vucic S, Gorman MP, Benson L, Alper G, Riney CJ, Barnett M, Parratt JDE, Hardy T, Leventer R, Merheb V, Nosadini M, Fung VSC, Brilot F, Dale RC. Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin 4 antibodies, and multiple sclerosis. Mult Scler. 2015 Jul 10.
  • Ramanathan S, Sato S, Matsushita T, Masaki K, Yamasaki R, Dale RC, Kira J, Brilot F. Antibodies to myelin oligodendrocyte glycoprotein are uncommon in Japanese opticospinal multiple sclerosis. Mult Scler. 2015 May 26. pii: 1352458515586089.
  • Ramanathan S, Mohammad S, Tantsis E, Nguyen TK, Merheb V, Fung VSC, White OB, Broadley S, Lechner-Scott J, Vucic S, Henderson APD, Barnett MH, Reddel SW, Brilot F, Dale RC. Australasian and New Zealand MOG Study Group. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):127-137.
  • Chen KA, Brilot F, Dale RC, Lafferty AR, Andrews PI. Hashimoto's encephalopathy and anti-MOG antibody encephalitis: 50 years after Lord Brain's description. Eur J Paediatr Neurol. 2017 Nov;21(6):898-901.
  • Brilot F. Relapsing ADEM followed by optic neuritis in children; a clinical entity associated with anti-MOG antibody. European Journal of Neurology 25(8):1003-1004.
  • Weissert R, Brilot F. Induction of Central Nervous System Disease by the Adaptive Immune Response. Front Immunol. 2017 8:1218.
  • Ramanathan R, O’Grady, G, Malone S, Spooner C, Brilot F, Dale RC. Isolated seizures as the first episode of relapsing MOG antibody-associated demyelination in children. Submitted for publication, under review.
  • Ramanathan S, Fraser C, Curnow SR, Ghaly M, Leventer RJ, Lechner-Scott, J, Henderson A, Reddel SW, Dale, RC, Brilot F. Novel inflammatory ophthalmological presentations associated with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis. Submitted for publication, under review.
  • Tea F, Lopez A, Zou A, Ramanathan S, Merheb V, Nguyen T, Lee F, White O, Broadley S, Lechner-Scott J, Vucic S, Henderson A, Barnett M, Reddel S, Kelleher C, Lunemann J, Dale RC, Brilot F on behalf of the Australian and New Zealand MOG Study Group. Conformational MOG is required for accurate human autoantibody binding. In preparation

Updated: 20 April 2018

Updated: 06 January, 2015

Investigator

Co-investigator

Grant Awarded

  •  Project Grant

Total Funding

  • $220,000

Duration

  • 3 years over 2015 - 2017

Contact Us

We're not around right now. But you can send us an email and we'll get back to you, asap.

Start typing and press Enter to search