New test to help with diagnosis of demyelinating conditions

New test to help with diagnosis of demyelinating conditions

14 October, 2019
  • Myelin oligodendrocyte glycoprotein (MOG) antibody is associated with many demyelinating conditions, but it has not be characterised in-depth.
  • A team of Australasian researchers looked at MOG antibody in demyelinating conditions to determine its features in different conditions.
  • In exciting findings, the researchers developed a new test that showed that MOG antibody levels are higher in more severe conditions, and its binding patterns are different depending on the condition.
  • This new test is currently undergoing approval for use in the clinic to help with diagnosis and disease course prediction in different demyelinating conditions.

What is myelin oligodendrocyte glycoprotein (MOG) and MOG antibody?

Myelin oligodendrocyte glycoprotein (MOG) is an important protein that makes up myelin, the insulating layer of the nerve fibres in the brain and spinal cord that is damaged in MS. Damage in MS is due to the attack of antibodies. Normally, antibodies are produced by the body to fight off infections, but sometimes they can mistakenly attack tissues in the body and in MS the antibodies are directed against the myelin. In many demyelinating conditions, it is MOG antibodies that lead to damage of the myelin. The presence of MOG antibodies has been associated with many demyelinating conditions in children and adults including optic neuritis, acute disseminated encephomyelitis (ADEM) and transverse myelitis. All of these conditions can present with symptoms similar to MS.

While the clinical spectrum of MOG antibody disorders has been explored, its response in different demyelinating disorders hasn’t been looked at much. Understanding the features of MOG antibody in different demyelinating conditions will improve diagnosis and management of these conditions.

What did the researchers do?

Published in Acta Neuropathologica Communications, MS Research Australia-supported researcher Associate Professor Fabienne Brilot-Turville and her team have characterised MOG antibody in 139 children and 148 adults with different demyelinating conditions. They developed a live cell-based test to detect MOG antibody – meaning the cells from these people are biologically active. The researchers then investigated whether there were specific binding patterns between MOG antibody and MOG in different demyelinating conditions that could help with diagnosis in the future.

What did the new test show?

All 287 people were positive for MOG antibody. In the children, ADEM was the most prevalent condition at 38% followed by optic neuritis at 25%. In adults, the most common condition was optic neuritis at 61%. The majority of children experienced a monophasic course of disease, which involves a single demyelinating event, while adults experienced a more relapsing course, regardless of the condition. There was no link between the amount of antibody and age. However, MOG antibody levels were higher in adults with optic neuritis in both eyes compared to those who had optic neuritis in one eye, regardless of the course of disease, suggesting that higher antibody levels are associated with more severe conditions.

And was the binding different?

The researchers then used techniques to modify the structure of MOG and add chemical modifications, and then tested the binding patterns across the different conditions. By doing this, the researchers identified specific MOG antibody binding patterns for different conditions. In particular, the binding patterns between MOG antibody and MOG were different for monophasic and relapsing conditions in adults – meaning that this feature could be used to predict whether someone is more likely to go on to have a relapsing disease.

What does this all mean?

These exciting findings show that the new test developed by Associate Professor Brilot-Turville could be used to refine and improve diagnosis of different demyelinating conditions. Also, the different antibody response seen between monophasic and relapsing conditions may be harnessed to predict people more likely to have relapses. This means treatment can be initiated faster to prevent further relapses. Relapses have been associated with increased disability over time, and it is vital to determine whether someone is likely to have a relapse earlier in the disease course.

Associate Professor Brilot-Turville says that “these findings provide a good opportunity to take advantage of these features of MOG antibody to detect relapsing conditions before it’s too late”.

These results highlight the disadvantages of the current antibody tests, which don’t take into account different binding patterns in various conditions. Associate Professor Brilot-Turville and her team are currently in the process of receiving accreditation from the National Association of Testing Authorities (NATA) to formerly recognise and promote the new test. This will bring us one step closer to predicting the disease course and personalising treatment for demyelinating diseases.

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