Martin Weber, MD, Discusses MOG-Mediated Disease in Multiple Sclerosis

In this podcast, Dr Weber discusses clinical presentations of myelin oligodendrocyte glycoprotein-mediated disease in multiple sclerosis, as well as important research developments in this field (transcript below). Dr Weber recently gave a talk about MOG-mediated disease in MS at the ECTRIMS/ACTRIMS MSVirtual2020 meeting.

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Martin Weber, MD, is affiliated with the department of neuropathology and neurology at the University of Göttingen in Germany.

Reference:
Weber M. MOG mediated disease. Talk presented at: ECTRIMS/ACTRIMS MSVirtual2020. September 13, 2020.

Transcript:

Christina Vogt: Hello everyone, and welcome back to another podcast. I’m Christina Vogt, managing editor of Neurology Learning Network. Today, I’m joined by Dr Martin Weber, from the department of neuropathology and neurology at the University of Medicine of Gottingen in Germany. Thank you for joining me today.

Dr Weber: Sure!

Christina Vogt: Today, we’ll be discussing myelin oligodendrocyte glycoprotein, or MOG-mediated disease in multiple sclerosis - a topic he recently discussed at MSVirtual2020. So first, could you discuss the clinical presentations of MOG-mediated disease in the context of multiple sclerosis?

Dr Weber: That is a super important question because we found out over time with colleagues that MOG-mediated disease has some differences in the clinical appearance, making it different from multiple sclerosis. And there are probably 2 important hallmark findings, which is bilateral optic neuritis, which is relatively rare in multiple sclerosis and very common feature in MOG-mediated disease. And the second clinical symptom is the involvement of the brainstem. So, whenever these 2 areas of symptoms are included, one should definitely consider the underlying disease being MOG-mediated disease.

Christina Vogt: What have been some important research developments in this field over the past year or so?

Dr Weber: Absolutely. There's been a tremendous amount of work from different groups all around the globe. So, it's really hard to decide which is the most important one. Let me think of 2 findings that are probably important and guiding us the way. One is that antibodies themselves–so, antibiodies against MOG in a certain context of an animal model, where animals already carry self-reactive T cells, are capable of inducing spontaneous disease, which is very similar to common EAE, which is usually actively induced but in this case, the antibodies themselves are capable of initiating the disease. And I think this has given us a strong hint that the antibody itself is pathogenic, at least in the right context of inflammatory milieu.

And then, the second finding, which is more from the clinical side, is that very conclusively, the work by [inaudible] now this year published, has shown that the cerebrospinal fluid is absolutely different from multiple sclerosis in its findings, and that the vast majority of our patients with MOG-mediated disease show absolutely normal CSF finding. So, this is another, let's say, piece or this is a junction, so to say, where one should definitely think of MOG-mediated disease if the CSF results come back normal while the MRI is–and also, of course, the clinical presentation–is compatible with multiple sclerosis or a related disease. So, this helps us tremendously because we always include the CSF in the diagnosis, and these, let's say not-so-MS-typical findings, normal CSF, will tremendously help us to delineate these patients.

Christina Vogt: What areas of future research are still needed in this field?

Dr Weber: I think 2 lines are probably extremely important. One is to definitely show the interaction that the antibodies themselves have within the immune system. So, relating to the earlier concept that they might be pathogenic themselves, about certainly in the interplay with other immune cells, most likely self-reactive T cells. And so, this understanding would then hopefully, or possibly similar to aquaporin-4-IgG-positive NMO, generate possibilities, to develop antigen-specific therapies because this is really what is needed in the entire field of CNS demyelinating disease, and I think identifying the antigen.

But then, secondly, also identifying how this antigen triggers different parts of the immune system to direct itself against the body would tremendously help us to develop specific therapies for this particular disease.

Christina Vogt: And lastly, what key takeaways about MOG-mediated disease and MS do you hope to leave with neurologists and neurology providers?

Dr Weber: Well, I hope to convince the majority of people that this is a different disease. So, this is a disease entity in its own right, and by saying this, this is not so much about being right or being wrong or proving that this is a different disease entity, but I think for a condition, it's extremely important to see red flags when things don't look like MS. And that's probably now, I mean, starting with NMO–that was the first disease that was successfully delineated from the core, so to say, disease MS.

And I think now, we are at the border of identifying the next disease entity, and I think it's very important for the clinician to see these red flags because therapy is dramatically different. So, B-cell -directed therapy should be initiated.

And then in the bigger picture, I think the findings that we developed now over the last 5 years should generate the hope and the understanding that probably MS as a whole can be understood if different disease entities, which might be included in the term multiple sclerosis, can be delineated. So, one strategy to understand MS better might be to look at differences between patients and identifying disease entities within this big group of disease. So, probably in the future, it's possible that we don't talk about MS as a disease entity anymore, but as a group of diseases, and that would probably help us to develop more specific therapies for each entity.

Christina Vogt: Thank you again for joining me today.

Dr Weber: Sure!

Christina Vogt: For more podcasts like this, visit NeurologyLearningNetwork.com.