Video Library

How does NMO Differ from MS? The Discovery of NMO IgG

Published on April 2, 2010

Sean Pittock:

At Mayo clinic, we’ve had an interest in NMO for about the last 10 years. The discovery of NMO-IgG and the concept that the target antigen in NMO is a water channel, the Aquaporin-4 water channel, has really resulted in a seismic shift in the whole thinking of inflammatory central nervous system [inaudible 00:00:26] diseases. I think it’s important to realize that despite spending billions of dollars on MS research, we really don’t really know what MS is.

Benjamin M. Greenberg:

To draw an analogy between multiple sclerosis and NMO allows us to understand why things are so exciting in NMO research. For years, Neuromyelitis optica had a phenotype, had an appearance that was similar to multiple sclerosis and it was actually a great way to start fights in meetings. Is Neuromyelitis optica part of multiple sclerosis or is it something completely separate? With the discovery, description and characterization of the antibody that we see in the majority of patients with NMO, we can now really uniquely define these patients biologically and really understand why do they act different than the multiple sclerosis patient.

Brian Weinshenker:

One can see how it would easily be confused with multiple sclerosis and it’s really now being differentiated to a much clearer extent because of an antibody test that was discovered around 2000 at our clinic at Mayo clinic.

Claudia Lucchinetti:

Although I’m a neurologist caring for patients, I kind of knew that it was at the lesion level, at the tissue level that I needed to make an impact to try and understand the disease. So actually I began then starting to take care of patients with NMO in the clinic. My colleague Brian Weinshenker was seeing them. I began seeing them and then I had a resource of tissue from patients with NMO who would’ve died later in their disease and that was back in 2000. And at that time I was really studying and looking carefully and making notes about the disease and what kept appearing in my notes. I kept saying, wow, bizarre astrocytes, this looks astrocytic. And then I presented that data at a meeting at Mayo just at a conference. And attending that conference was Brian Weinshenker and Vanda Lennon. And I was showing this unique pattern of tissue injury and Vanda and Brian both approached me after and said I think we have something here.

Brian Weinshenker:

So it crossed my mind some years ago. Why is it not true that some patients that have transverse myelitis, especially those that have recurrent episodes, why don’t they have some form of Neuromyelitis optica? And at that point we and some other groups begin to recognize that the myelitis was much more severe and there were long lesions that we would see in the spinal cord on MRI scans when patients would have an attack. And this allowed us to come up with diagnostic criteria that we felt were very good at differentiating Neuromyelitis optica from MS. But I don’t think many people believed us. They said, well, this is really all the same thing and there’s no way to exactly differentiate

Sean Pittock:

Vanda Lennon who’s an immunologist, who’s the director of the Neuroimmunology lab talked with Brian Weinshenker after the meeting and said, “Look, why don’t you send me blood samples in these patients and I’ll look at them and see if we can identify an antibody.” And that’s how this originated. She found in 70% of the patients that he sent a florescence pattern that was identical in all the patients.

Claudia Lucchinetti:

That really led to a confluence of events. Vanda studying in the lab, me studying the tissue, Brian’s sitting the clinical all at Mayo, but all converging at once to begin saying, well, I think we have something here. So then they did the pivotal study to track all the patients, found this biomarker and lo and behold, this was the first biomarker that could really stratify a disease.

Brian Weinshenker:

It wasn’t really until we discovered this antibody marker, I think that really changed people’s mind because it segregated perfectly with the clinical criteria that we established that distinguished Neuromyelitis optica from MS. And then people could use this antibody test at a very early point, and when patients who were detected that were positive for the antibody were followed and it was almost like a crystal ball. It would predict their course and we would say this is probably what would happen, and indeed that’s what happened. I think people started to listen.

Michael Levy:

With the NMO-IgG now, we had something that we could focus in on, at least rule out and if ruled in, it gave researchers something to put our fingers on and say, this antibody is only found in NMO patients. What does it mean? It really just started guiding us towards Aquaporin-4 and the NMO-IgG. What its role is and it’s really been a boost in the field.

Brian Weinshenker:

We’re optimistic that one day we’ll be able to better predict what’s going to happen to patients and know better how to treat them. Maybe we wouldn’t need to wait until they have an attack to know that our treatments ineffective. We would just be able to measure the antibody level and perhaps have a specific antibody with a certain activity and be able to say, oh, were our treatments not working? We have to switch treatments and not wait for a new attack.

Benjamin M. Greenberg:

The moment we make insights like that, then you really start talking about cures because once you have the biology that associates with the phenotype, then you can work backwards and say, how do we stop that from happening?

Katja Van Herle:

So what we know is we’ve now got the NMO-IgG antibody. We can screen patients that have disease states that probably aren’t MS, that aren’t getting treated right. We understand that there are totally different drugs for NMO-IgG positive spectrum disease. We also have somewhat of an understanding for patients who have no antibody but also present only with cord, spinal cord disease and eye disease. That’s totally different than Devic’s disease. In fact, if we’re doing everything correctly in this foundation, we should never see that again. Devic’s disease should be something of the past.


Posted in

Leave a Comment

More Videos from

Can Tissues injured by NMO be repaired (Regeneration/Remyelination)?

The short answer is yes. The long answer is we don't know how that happens...after a patient relapses and we suppress the inflammation

Currently how is NMO/NMOSD best diagnosed?

Since the discovery of the APQ-4 antibody in 2004 the spectrum of NMO has dramatically changed and evolved to what we now consider NMOSD.

Do NMO treatments have dangerous side effects?

In NMO, the immune system is too active, so all of our treatments are really directed at decreasing the immune system.

Does spinal cord damage occur in NMO?

Spinal cord damage occurs in all patients with NMO, because it's one of the essential diagnostic criteria for NMO.