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Published: Jan. 12, 2015, 11:21 p.m.

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Hello, and welcome to Episode Twenty-Seven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I\u2019m your host, Dan Keller.

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This week\u2019s podcast features an interview with Dr. Brenda Banwell about a new journal on multiple sclerosis and related disorders, of which she is a co-editor-in-chief. But to begin, here\u2019s a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.

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This week we published two stories related to articles published in the December 2014 issue of JAMA Neurology. The first article is about the interim results of the Halt MS trial. In this phase 2 clinical trial, physicians performed autologous hematopoietic stem cell transplants on 24 patients with relapsing-remitting MS. In other words, the team obliterated the patients\u2019 existing immune systems and attempted to hit the reset button by infusing the patients\u2019 own stem cells. Three years after the treatment, 78% of patients showed no signs of disease activity, significantly higher than similar studies using conventional MS treatments. However, not everyone is popping the champagne yet. Some are concerned that the treatment may not have been aggressive enough to eradicate the patients\u2019 entire immune systems, and it will be only a matter of time before some patients start showing signs of disease activity once more. Others are concerned that the treatment was unnecessarily intense and risky, suggesting safer methods of stem cell transplant would be effective in resetting the immune system.

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Halt MS is one of the trials using a new primary outcome measure called \u201cno evidence of disease activity\u201d or NEDA for short. NEDA is basically a fancy way of saying \u201cremission\u201d; that is, no relapses, no disability progression, and no new lesions on MRI. NEDA sets a new treatment standard for patients and their doctors, reflecting the hope of a new generation of disease-modifying therapies.

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But is NEDA really a feasible clinical care target? Our second story this week takes a look at this issue with the first real-world cohort study. Researchers asked how many people with relapsing-remitting MS maintained NEDA status seven years after diagnosis. While that goal remained elusive for all but 8% of patients, NEDA status at two years was highly predictive of no disease progression at seven years. Many questions remain about NEDA. But in an editorial accompanying the study, researchers suggest that NEDA is still a worthy, albeit very ambitious, goal.

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What do you think? Let us know on the discussion forums at msdiscovery.org/forums/discussion.

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Now to the interview. Dr. Brenda Banwell is Professor of Neurology and Pediatrics at the Perelman School of Medicine of the University of Pennsylvania and is chief of the Division of Neurology at The Children\u2019s Hospital of Philadelphia. We met to talk about a fairly new journal called Multiple Sclerosis and Related Disorders, of which she is one of the co-editors-in-chief.

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[Interview]

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Interviewer \u2013 Dan Keller

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I\u2019m here at The Children\u2019s Hospital of Philadelphia with Dr. Banwell, and someone from the public affairs office is here with us. I\u2019m just wondering why did you see a need for a new journal?

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Interviewee \u2013 Brenda Banwell

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At the time that we launched Multiple Sclerosis and Related Disorders, there were journals focused solely on multiple sclerosis and journals on neurology broadly, but not one that focused specifically on multiple sclerosis and the various and increasing number of demyelinating disorders of the central nervous system that are being recognized. So Multiple Sclerosis and Related Disorders was meant to be a home for sometimes comparisons, sometimes new insights, and certainly thoughtful reflection on the scope and breadth of demyelinating disorders in the central nervous system in adults and in children.

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MSDF

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Is there a certain amount of waiting, or it\u2019s just the volume of papers that you get in that determines the mix between multiple sclerosis and other demyelinating disorders?

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Dr. Banwell

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Really it\u2019s actually the quality of the papers we receive that drive the selection into the journal. To date, we have been blessed to receive some very interesting manuscripts, some of which relate to multiple sclerosis but many others relate to neuromyelitis optica, which is one of the disorders we were interested in; in antibody-associated encephalopathies; in patient perceptions of demyelinating disease, which is from the area that I think is very interesting and relevant; and then even some basic science, manuscripts that have looked at mechanisms of the immune system targeting the central nervous system.

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MSDF

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Is there a particular editorial philosophy?

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Dr. Banwell

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I guess the one my co-editors and I would say that we\u2019re looking for manuscripts that push the envelope a little bit in terms of hypothesis generation. We like to see a thoughtful reflection on where the next step needs to be in the papers that we accept. And we\u2019re not at all uncomfortable with being a little bit provocative in terms of perhaps people broaching new hypotheses as long as those hypotheses are well defended and can generate the next step of research.

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MSDF

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So it sounds like you\u2019re also delving into basic science, or at least early clinical studies here, too?

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Dr. Banwell

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We\u2019ll delve into it. We are not a basic science journal, so we would not pretend to be Cell or Nature or any of those sorts of journals. But certainly many of the manuscripts that we\u2019ve accepted have discussed potential hypotheses based on basic science research and how that might tie to the clinical picture.

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MSDF

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One question that always arises with a new journal is why should people want to publish in this journal as opposed to some of the more established ones?

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Dr. Banwell

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Well, I think like any new journal, we have a lot of opportunity to accept manuscripts. We have very quickly gotten to the point where we have a very high caliber of manuscripts, which I think speaks to the interest in the field, so the journals that are arguably in competition with us are also now increasingly receiving high quality manuscripts as well. And I think overall it reminds us that there is actually quite a bit of research going on in multiple sclerosis and related disorders, and therefore there\u2019s room for several journals in the field at this time.

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MSDF

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Is it now being indexed in PubMed?

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Dr. Banwell

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We have applied for indexing and we\u2019ll hope to hear very shortly.

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MSDF

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Is there any problem or have you faced any barriers?

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Dr. Banwell

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No barriers. It\u2019s just that you have to have a certain number of manuscripts published, you have to show that the manuscripts are of high quality, and you have to have been in the field long enough to actually have enough publications for them to judge the quality of what we\u2019re doing.

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MSDF

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I see that you have co-editors-in-chief. Who are your colleagues in this?

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Dr. Banwell

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So there\u2019s Dr. Chris Hawkes and Dr. Gavin Giovannoni from England, and Dr. Fred Lublin from the United States.

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MSDF

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Anything else important to add about the new journal or the things that it\u2019s come out with lately?

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Dr. Banwell

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Well, we have a lay review author as well, and we do hope to increase some scholarly input from the lay public over time. Certainly we\u2019re interested in maintaining the sort of price we put on novelty and in encouraging people to submit work that is perhaps looking at a new angle in the field. I think the related disorders aspect of our journal is an important component, both of the title and also of the concept. We are particularly interested in some of the emerging disorders that we now realize are potentially, if not multiple sclerosis, certainly in the field of immune-directed responses in the central nervous system. So I think that aspect of our journal speaks to an area of the field that might not have been previously quite so well captured in the existing journals.

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MSDF

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Does this journal lend itself to a more global approach to demyelinating diseases, since it\u2019s multiple sclerosis and related disorders as opposed to just looking at MS as an isolated condition?

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Dr. Banwell

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Certainly in concept, yes. I think in fairness to the other journals that I think are all excellent and also in the field, we are not the only ones that are broadening the scope. And I think that speaks to the discoveries. So with the identification in 2004 of the aquaporin-4 antibody, and then subsequent to that really compelling evidence that the aquaporin-4 neuromyelitis optica story broadened and recognized a very specific subgroup of patients, that is also happening with other antibodies potentially, and there\u2019s some emerging information about, for example, NMDA receptor encephalitis and other disorders that weren\u2019t really recognized as such a few years ago. Our journal is prioritizing this type of sort of patient base and diagnostic categories, but so too are other journals that are also excellent in the field. So I think in fairness, everyone is recognizing that there\u2019s more to the story.

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MSDF

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Is the NMDA antibody story with the catatonia?

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Dr. Banwell

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So NMDA receptor encephalitis is a disorder actually discovered by Josep Dalmau at Penn, so very near and dear to our heart here. The patients present sometimes with psychotic features, they can become quite catatonic. There\u2019s been some lay publications on that. \u201cBrain on Fire\u201d was a book written by a survivor of NMDA receptor encephalitis. In children we certainly see \u2013 and in adults, but certainly in children \u2013 we see a number of patients present with severe seizures and then with abnormalities of movement. When these patients present they can be catastrophically ill, often in intensive care unit. Over time as the patients recover, miraculously it seems because it really does appear to be quite miraculous, the patients can have a full recovery. So it is a disorder that\u2019s extremely important to recognize and can be misdiagnosed quite easily as an infectious encephalitis, as initially other psychiatric disorders, and in some patients as a really severe form of epilepsy, all of which it is, but it has a better overarching diagnosis. And making the diagnosis certainly gives hope in terms of long-term prognosis, and we do use specific therapies for the patients with the diagnosis.

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MSDF

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Very good, I appreciate it. Thanks.

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Dr. Banwell

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My pleasure.

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Thank you for listening to Episode Twenty-Seven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF\u2019s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.

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Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.

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We\u2019re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.

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