PURPOSE OF REVIEW: The discovery of neuromyelitis optica (NMO)-immunoglobulin (Ig)G and its target antigen aquaporin 4 (AQP4) redefined NMO, historically considered a multiple sclerosis (MS) variant, as a specific disease entity. NMO and MS have divergent responses to immunotherapy and it is important to distinguish the conditions at disease onset. In this article, we review new pathological, imaging and clinical trial data pertaining to NMO, and discuss emerging concepts of molecular immunopathogenesis in NMO that can inform the development of targeted therapies. RECENT FINDINGS: Recent studies illustrate the range of brain lesions associated with NMO, and the importance of diagnostic biomarkers in patients with atypical or limited presentations. Neuropathological studies showing perivascular astrocyte destruction and preserved myelin in early NMO lesions indicate a pathogenesis distinct from MS. Characterisation of NMO-IgG binding to AQP4 isoforms and the development of novel disease models have elucidated complement-mediated and cell-mediated mechanisms of astrocyte injury. SUMMARY: NMO-IgG positive NMO is not an MS variant. Further work is required to delineate the pathogenesis of NMO syndromes without antibodies to AQP4. Methodological flaws inherent to small, open label trials of current NMO therapies limit extrapolation to clinical practice. In the coming years, NMO will be treated with targeted therapies that are emerging from an enhanced understanding of the molecular immunopathogenesis of the disease.

Barnett MH, Sutton I; Current Opinion in Neurology (Apr 2012)
http://www.docguide.com/neuromyelitis-optica-not-multiple-sclerosis-variant?tsid=5

TMA Older Teen/Young Adult Survey

If you are 16 to 35 years old, we need your help … and it will take less than ten minutes. Please forward this email to your friends who have TM, ADEM or NMO.

The first retreat weekend for older teens and young adults was held in 2006 at Victory Junction in North Carolina. This retreat was a powerful experience where for the first time, many young people met others with TM, NMO and ADEM. The physicians and researchers from our medical advisory board attended camp and provided a wonderful educational program. Our doctors also made themselves available to our members and their families throughout the retreat, and offered excellent guidance and support. These retreats have been going on every other year and we are interested in continuing this important program for our young people.

We are requesting your opinions and ideas in order to design a program that most effectively meets your interests and needs. We are asking people who are between the ages of 16 and 35 to fill out our survey so that we can make informed decisions about what program we should be offering to the young people in our community. Even if you have no interest in the program or would not plan to attend, we would be interested in receiving your perspectives. The survey will only take you ten minutes to complete.

We will not disclose anyone’s personal information when we do the analysis or present the results of the survey. Your anonymity will be protected and your name will not be associated with the responses you provide us. At the end of the survey, there will be a link which will take you to a completely separate document where we will ask you to provide us with your contact information. It is very important for us to have your contact information for the purpose of planning the retreat and involving you in this planning process. We would also use this information to keep you updated about our plans as they are developed.

Please begin the survey by clicking on the following link:

http://www.surveymonkey.com/s/TMAYoungAdults

Thank you for your time and your thoughtful responses.

Sandy Siegel
President
The Transverse Myelitis Association
ssiegel@myelitis.org
http://www.myelitis.org

The Women's Conference Presents

Response by Victoria Jackson, Founder of The Guthy-Jackson Charitable Foundation

I don't want to do anything too ambitious. Maybe lose 5 pounds. Take a cooking class. Oh. There is one more thing. I'm going to cure a rare disease called NMO (Neuromyelitis Optica). A year ago, my 16-year-old daughter got the diagnosis. NMO is one of about 7,000 diseases that are so rare that little or no money is spent on research, prevention, medicines or cures -- the bottom line being they don't have profit potential. Last year, my husband Bill and I created a Foundation to do just that. We had a three-day symposium in November, and brought doctors in from Harvard, Stanford, the Mayo Clinic, Scripps, and even England and Japan, but the biggest deal was Patient Day (my daughter's idea; why can't I be more like her?) -- we flew in those who have NMO, and their families. 

Now, for the first time, there's an NMO community. One day my daughter said, "Mom, this is bigger than you and me." She's right. That little piece of wisdom got me right out of my own personal fear and into warrior mode. If we find the cure for NMO, that might be the domino that knocks down MS and a lot of other autoimmune diseases. So NMO is going to stand for NO MORE ORPHANS. 

But first things first: MY 2010 TO DO LIST: 

1) CURE NMO (Neuromyelitis Optica)

2) Once that's done, begin curing all orphan diseases

3) Start cooking class

4) Lose 5 pounds

5) Lose five more if cooking class goes well

This text is a post from The Women's Conference, XX-Effect website.  To read the original post please visit: http://www.womensconference.org/victoria-jackson-2/  and to read more posts please visit: http://www.womensconference.org/xx-effect-2010-to-do-list/ 

New NMO Clinical Trial

Now enrolling at the Mayo Clinic

Mayo Clinics in Minnesota and Arizona have launched a new clinical trial for NMO patients. The purpose of the database is to determine if eculizumab, a monoclonal antibody that interferes with complement activation, reduces the frequency of NMO attacks or improves outcome.

The Primary Outcome Measures the reduction in number of NMO attacks and determines safety for NMO.The Secondary Outcome Measures improvement in the quality of life, visual function and walking, and determines drug levels in blood and CSF.

Experimental Drug Intervention:

The patient will receive eculizumab at a dose of 600mg intravenously (by infusion into the vein) each week for

4 weeks, 900mg intravenously at the fifth week, and 900mg every 2 weeks for 48 weeks.

The first infusion will be given at Mayo Clinic (Minnesota or Arizona); subsequent infusions will be

administered at home by a nurse employed by Coram Home infusion services (coordinated by a Study

physician).

Eligibility

Patients must be NMO-IgG seropositive, and have a diagnosis of NMO (defined by 2006 criteria) or an NMO

spectrum disorder (recurrent optic neuritis or longitudinally extensive transverse myelitis).

Clinical evidence must document at least 2 relapses in the past 6 months or 3 relapses in the past 12

months (at least 1 relapse in the preceding 6 months).

The patient must be at least 18 years old.

If you are interested in this study and would like to learn more about it, please contact the investigators at the following locations:

Mayo Clinic - Arizona Principal Investigator: Dean M. Wingerchuk, M.D.

Contact: Irene Galasky 480-342-6104

galasky.irene@mayo.edu

Mayo Clinic - Minnesota Principal Investigator: Sean J. Pittock, M.D.

Contact: Karen Brekke 507-538-3761

brekke.karen@mayo.edu

Contact: Connie Brekke 507-266-3196

brekke.connie@mayo.edu

For more information please visit http://clinicaltrials.gov/ct2/show/NCT00904826

Why Should We Care About NMO?

A year ago, my 16 year-old daughter was diagnosed with a rare disease called NMO (Neuromyelitis Optica). NMO is what they call an “orphan disease”—meaning, not enough people have it to justify the time, money and energy required to effect a cure. Last year, my husband Bill and I created a Foundation to give grants to doctors and researchers—and bring those “orphans” together.

I knew it would be tough to get the world to care about an illness that so few of us have. Most people are too kind to say that in so many words, but I’d like to tell you why NMO matters.

That’s the question I always want to be asked first. Because it would probably be the question I’d ask. I’ll answer with another question: What are the requirements of compassion? In the Not-So-Golden Age of reality shows and the 24-hour news cycle, what does it take to get our attention? A police chase? Genocide? Celebrity scandal? I think what it comes down to is the quality of the attention we choose to give; that defines our humanity, our “tribe.” Look, I’m a mom. When my daughter was diagnosed with NMO, I did what any mom would do: after the tears, I went into battle mode. But unlike most moms out there, I had the resources to build an army, and create a Foundation.

If you asked, Would curing NMO help unlock the cure for other diseases, like MS? Probably. But let’s take NMO and MS out of it—and ask the question again. Why should we care? The answer simply is, “Because caring is the best part of us.” Don’t get me wrong, I’m on a mission. I will save my daughter. But it’s become much bigger than that. Through the Guthy-Jackson Foundation, I’ve adopted a lot of orphans. I have a whole new family—dads and daughters, moms and sons. That was something I could never have imagined, and it has filled my heart. So: Why should we care? Because caring fills the heart and soul, and is the very best part of who we are—and who we can be.

—Victoria Jackson

Q & A about Neuromyelitis Optica Spectrum Disease with Ben Greenberg, M.D, M.H.S. 

A top clinician in NMO, Dr. Benjamin Greenberg talks with Spectrum about NMO treatment, diet and more...

 Q - What are the most effective treatment options?

To date there are several options for treating neuromyelitis optica, such as rituximab (Rituxan®), mycophenolate mofetil (Cellcept®) and azathioprine (Imuran®). There have been no head to-head trials of these agents, but they all have data to support their use in NMO. Choosing amongst them is based on pros and cons that are specific to each individual patient.

Q - What are the long-term effects of treatments including steroid infusions?

The long-term effects of treatments are dependent on the treatment used and can be quite variable. In general, here is a partial list of known long-term effects that should be considered:

1. Steroids – long-term exposure to steroids can increase the risk of diabetes, hypertension, highcholesterol, cataracts, osteoporosis and infections. Therisks are related to both the duration of exposure and dosage used.

2. Rituximab (Rituxan®)– There are no long-term studies looking at risks of exposure to rituximab. In the short term, the biggest risk is of infections. There have also been reported cases of a brain infection, called PML (progressive multifocal leukoencephalopathy) in patients on rituximab, although the link is unclear.

3. Mycophenolate mofetil (Cellcept®) and Azathioprine (Imuran®) – The major long-term risk of these agents is infection. In studies that followed transplant patients who were receiving these drugs for 10 years or more, there was an increased risk of certain cancers – including lymphoma and melanoma. This risk seems to be

lower with mycophenolate, but this data is limited. Based on the risks, patients on one of these agents should wear hats, sunscreen and have annual dermatologic exams.

Q - Are there side effects to so much exposure to MRIs (such as cancer)?

Great question. The short answer is, “No.” MRIs are very different than Xrays and CT scans – there is NO radiation. MRIs have been around for more than 20 years. While there have been no formal studies tracking patients over time, there are also no indications that repeated exposure to a MRI machine increased any health risks. There are dangers to a MRI if you have implanted devices or metal, because it uses such a huge magnetic force, so discuss the short-term safety with your doctor if this applies to you.

Q - What is the most effective treatment for stopping attacks?

I wish I knew. Anecdotally, rituximab, mycophenolate mofetil and azathioprine probably are about equally effective, but there are some patients who clearly have a better response to one or the other drug.  We can tell who is who yet, so in general we say start with one and switch if a relapse occurs or side effects occur.

Q - How does diet affect most NMO patients?

We don’t know! There are no studies assessing the role of diet in groups of NMO patients. From experience, I can tell you that the better the general health of a patient, the better they do with the ups and downs of NMO. Some patients find a selective diet they feel help their disease and this is fine, as long as there is adequate balanced nutrition.

Q - What is the current main approach to curing NMO?

There are many active NMO programs around the world trying to cure this disease. Our treatments are good, and for some they are potentially cures. But some patients continue to have relapses despite therapy. New drugs are being evaluated all the time and new treatment modalities are in clinical trials. The approach to a cure is very individualized. I recommend that if a patient is not responding to one of the first-line therapies mentioned above, that they seek care at a tertiary center with specific programs in NMO.

Q - Anything else?

The one thing I would add is that there is tremendous hope in the world of NMO. I would argue, potentially more hope than in diseases such as MS. Understanding this disease is accelerating and new treatments are on the horizon. The medical and scientific processes can never go fast enough for our patients struggling with these issues every day, but it is moving. There is every reason to believe that true cures for this disease will be found.

Dr. Greenberg is the Deputy Director of the Multiple Sclerosis Program and Director of the new Tranverse Myelitis and Neuromyelitis Optica Program at University of Texas Southwestern Medical Center.