The Pauline H. Siegel Eclipse Fund

Last week, we published a blog about the first FDA sanctioned cell therapy to promote repair through myelin regeneration in Transverse Myelitis, which is set to begin in 2018. We are extremely excited about this study, and are so happy that you are excited as well!

This study requires funding. The CONQUER program at UT Southwestern secured a one and a half million-dollar gift to fund the clinical portions of the phase I trial. The TMA has been working through The Pauline H. Siegel Eclipse Fund to raise money to cover non-clinical costs of the trial. If we raise all the money needed, we expect to begin enrollment in mid-2018. Every dollar you donate to The Eclipse Fund will be matched by a generous donor up to $150,000.

The Eclipse Fund was established in memory of Pauline H. Siegel. Pauline sadly passed away on Tuesday, August 15, 2017. It was Pauline’s 1994 diagnosis of TM that catalyzed the formation of the TMA. For over 20 years, she worked with her husband and TMA President, Sandy Siegel, to educate, support and inspire others in the TMA community. Despite the difficulties she faced, Pauline always managed to see and feel the blessings of her experience, and never lost hope for a better tomorrow. Pauline lived her life trying to improve the future of other people with TM and other rare neuro-immune disorders – NMOSD, ADEM, ON, and AFM. She was a powerful advocate, and touched us all with her compassion and vitality.

Pauline’s is a legacy of hope and, in her name, we will drive research forward to find a cure for rare neuro-immune disorders and enable spinal cord repair. To learn more about The Pauline H. Siegel Eclipse Fund, please watch the video below:

The fund will be used to support and accelerate the TMA’s research portfolio to fund discoveries that will directly impact the quality of life for the members of our community. The Pauline H. Siegel Eclipse Fund will drive critical research to:

  • Restore Function The first FDA approved cell therapy to promote repair through myelin regeneration in Transverse Myelitis is set to begin in 2018. The Transverse Myelitis Association, Q Therapeutics, and The University of Texas Southwestern are collaboratively sponsoring this first human safety study to treat central nervous system disease.
  • Identify Genes and Causation Research at Johns Hopkins University has shown a gene mutation (VPS37A) that is currently known to be present only in Transverse Myelitis patients. The Eclipse Fund will support the validation of this gene and its role in causation.
  • Improve Diagnosis Biomarkers and novel imaging techniques, once identified and validated, help accurately diagnose myelitis in the acute phase. Recent studies funded by the TMA and conducted by the Rare Genomics Institute and The Johns Hopkins Transverse Myelitis Center have revealed an antibody in TM patients that needs further investigation and has the promise of unveiling more details about the biology of the disorder.
  • Investigate Novel Therapies The Eclipse Fund seeks to fund the development of scientific models of disease that can be used to test existing drug therapies. The goal is to ensure that all potential therapies for restoration and repair are investigated.
Think people should hear about this?

Are Remyelination Strategies Realistic?

At the 2017 Rare Neuro-Immune Disorders Symposium, Dr. Benjamin Greenberg from the University of Texas Southwestern Medical Center gave a talk about remyelination strategies and announced the beginning of a Phase I trial in transverse myelitis. This is the first FDA sanctioned cell therapy to promote repair through myelin regeneration in Transverse Myelitis, which is set to begin in 2018. The University of Texas Southwestern, Q Therapeutics, Inc. and The Transverse Myelitis Association are collaboratively sponsoring this first human safety study to treat central nervous system disease.

How did this trial become reality?

Dr. Greenberg presented the stages of clinical research. The first step is preclinical development to develop the agent, whether it’s a cell or a molecule that then has to be tested for efficacy. The next step is to prove that there is no obvious or expected toxicity from that therapy. This preclinical development can literally take years or even decades to complete. In the United States, regulatory approval is required through the FDA where they grant what’s called an IND, or an Investigational New Drug application. A phase I trial is primarily meant to measure safety. As long as we make sure an intervention is safe, then phase II and phase III studies get approval to market that therapy to the rest of the world.

How does this cell therapy remyelinate?

Q therapeutics developed a glial-restricted precursor cell that develops into oligodendrocytes. Oligodendrocytes are cells that produce myelin, the insulation around nerves. In mice that are born with nerve cells without myelin, these cells have been shown to produce myelin.

Where are we now?

UT Southwestern and Q Therapeutics, with input from the TMA, collaborated and put in an IND application to the FDA, that was granted in July 2017. This means the FDA gave us approval to move into human remyelinating trials for transverse myelitis in a Phase I trial. This type of study requires funding. The CONQUER program at UT Southwestern secured a one and a half million-dollar gift to fund the clinical portions of the phase I trial. The TMA has been working through The Pauline H. Siegel Eclipse Fund to raise money to cover non-clinical costs. If we raise all the money needed, we expect to begin enrollment in mid-2018. The phase I trial will include nine non-ambulatory adult transverse myelitis patients who are more than a year out from their diagnosis.

How can you get involved?

If you are interested in learning more about this trial and other research, please fill out this form. You can also contribute to The Pauline H. Siegel Eclipse Fund to raise money to cover the cost of the trial. Every donation received will be matched dollar for dollar up to $150,000 by a generous anonymous donor.

Think people should hear about this?

What is Anti-Myelin Oligodendrocyte Glycoprotein (MOG)?

As researchers continue to study disorders like neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS), we are learning more and more about factors that contribute to the disease processes seen in these conditions. For example, demyelination from MS is thought to be caused by the activation of white blood cells called T cells (and maybe B cells), while most cases of NMOSD involve antibodies to aquaporin-4 (anti-AQP4 or NMO-IgG). There has recently been more discussion about Myelin Oligodendrocyte Glycoprotein or MOG, and its relationship to NMOSD. Although MOG’s exact function is not fully known, it is thought to be an important glycoprotein that influences the myelination of nerves in the central nervous system. Anti-MOG antibodies have been found in individuals diagnosed with NMOSD who do not have antibodies to AQP4, in acute disseminated encephalomyelitis, transverse myelitis, and optic neuritis. Those with anti-MOG NMOSD tend to have attacks most often in the optic nerve, or optic neuritis (ON), but can also present with inflammation in the spinal cord (transverse myelitis) and brainstem.

Recently at The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting, there was a discussion about anti-MOG and whether it should be its own diagnostic category or another variant of NMOSD. Dr. Douglas Sato of the Brain Institute of the Rio Grande do Sul in Porte Allegre, Brazil, argued that there are enough differences between anti-MOG disease and NMOSD, and proposed that it be called MOMEN, an acronym for “anti-MOG associated optic neuritis, encephalitis and myelitis (MONEM).” In contrast, Dr. Roman Marignier of the Hospital Pierre Wertheimer of Lyon University Hospital in France argued that anti-MOG disease is a variant of NMOSD that occurs without antibodies to AQP4. His argument was that patients with anti-MOG and patients with anti-AQP4 disease have similar cerebrospinal fluid characteristics, clinical characteristics, MRI characteristics, and the same acute and long-term treatment options.

Another presentation at ECTRIMS described a study that followed 33 children and 26 adults who were anti-MOG-positive over an average of five years. Researchers from the Kids Research Institute at the Children’s Hospital at Westmead in Sydney, Australia, found that 54% of all patients developed optic neuritis as their first disease sign. They found that the individuals in the study responded well to steroids, but relapsed when steroids were stopped. They found that their study participants had reduced relapse rates when they were on maintenance steroids, intravenous immunoglobulin (IVIg), or immunosuppression with rituximab or mycophenolate. 

Participate in Research on anti-MOG

Dr. Michael Levy and the NMO lab at Johns Hopkins University are developing tests for Anti-MOG (myelin oligodendrocyte glycoprotein) disease. They are especially looking for participants with recurrent clinical events of optic neuritis and/or transverse myelitis with either a negative anti-AQP4 antibody test or a positive anti-MOG antibody test from another lab. You can find more about the research here: https://myelitis.org/clinical-studies-and-trials/neuromyelitis-optica-anti-mog-disease-transverse-myelitis-optic-neuritis-biorepository/.

Think people should hear about this?

Understanding Disability Identity and Implications for Future Study

TMA Board Member and Paralympian Dr. Anjali Forber-Pratt and her colleagues recently published a systematic review of studies on disability identity development. In past years, psychologists and researchers have developed models of both identity development and disability identity development. Dr. Forber-Pratt is interested in how individuals develop their disability identity, and believes this research could be critical in developing support systems for individuals with disabilities and the greater disability community. By conducting a review of existing articles, the researchers aimed to provide individuals with disabilities, community leaders, special educators, counselors, psychologists, and the disability community with more information on the process of disability identity development.

The researchers searched academic journal article databases for their search of studies. Results were limited to peer-reviewed articles written in English between 1980 and 2017. Of the 144 articles they found, 41 were included in the researchers’ review.

The researchers’ review yielded two main findings. First, disability identity shapes the way individuals see themselves, their bodies, and interactions with their surroundings. People with disabilities not only have to navigate physical components of their disability but also what social meaning is attributed to that disability. These physical and social aspects combine to form a person’s disability identity, which should be considered both in relation to other intersectional identities (such as LGBTQ, racial identity, cultural identity, etc.) and independent of other aspects of identity. The second finding from this review is that disability identity development has been studied mainly through qualitative measures rather than quantitative measures. Larger scale studies that use a more comprehensive approach are needed to better understand disability identity development. Support is needed for research that spans across different disability groups to better understand the effects of multiple disabilities on a person’s development of disability identity.

This literature review highlights the need for awareness of disability identity development, especially for individuals and organizations that impact the lives of people with disabilities. This is especially true of rehabilitation professionals, educators, and caregivers, who are often able-bodied which can cause tension and cause the person with a disability to seek out support independently. Additionally, with more research, we can gain a better understanding of disability identity development and create interventions that better assist individuals who are in the process of developing a disability identity. Another finding of this literature review is that disability identity includes both an acceptance of one’s disability as well as involvement with the disability community. Large-scale, community level research is needed to learn more about the role the disability community plays in identity development.

There are barriers that can prevent people with disabilities from participating in research. For example, people may be reluctant to participate in research or may not have access to materials. Some people may not wish to be identified with having a disability at all. Also, there were few studies which included individuals with higher support needs, such as those with adaptive communication devices or those who have more than one co-occurring disability. These barriers are representative of the struggle people with disabilities face with accessibility and social stigma.

Forber-Pratt AJ, Lyew DA, Mueller C, Samples LB. Disability identity development: A systematic review of the literature. Rehabil Psychol. 2017 May;62(2):198-207. doi: 10.1037/rep0000134. Epub 2017 Apr 13.

Think people should hear about this?

How to Participate in Genetic Study of Transverse Myelitis

Earlier this summer, we published a blog post about a rare genetic mutation found in familial transverse myelitis. The mutation, named VPS37A, was discovered in two sisters who were both diagnosed with TM at different points in their life. Dr. Michael Levy screened an additional 86 TM patients and found another patient with the same rare mutation. According to Dr. Levy, “It is statistically beyond coincidence to find three human beings with this same rare genetic mutation unless it has something to do with the rare disease they all share, TM.”

Dr. Levy and his colleagues at Johns Hopkins University have recently been awarded a research grant from the TMA to continue studying this genetic mutation in TM patients. The study will be conducted by collecting DNA samples from consenting participants using saliva kits. Dr. Levy hopes to recruit TM patients from across the United States and potentially worldwide. Travel will not be required to participate in this study as the saliva kits can be mailed, and clinical information can be provided electronically.

If you are interested in participating in the study, please visit our website. Additionally, Dr. Levy will be conducting on-site DNA sample collections at the TMA’s 2017 Rare Neuro-Immune Disorders Symposium (RNDS) in Columbus, OH on October 20th-21st, so participation in the study will be accessible to all who attend. Please indicate your research interests when you register for the RNDS.

The potential implications of this study are vast, as this is the first finding of a genetic cause of transverse myelitis. Although the study may yield only a small percentage of TM patients with the VPS37A genetic mutation, it can still help researchers learn about other cellular and immunological mechanisms that play a part in transverse myelitis.

Think people should hear about this?

Acute Demyelinating Events Following Vaccines: A Case-Centered Analysis

This a summary of an article that was published in 2016 by Roger Baxter et al. in the journal Clinical Infectious Diseases.

A study was conducted to determine whether vaccines may have a causal effect on Transverse Myelitis (TM) and Acute Disseminated Encephalomyelitis (ADEM). Previous studies consist of mostly anecdotal case reports which do not look at population-level data and do not allow us to see if vaccinations were the cause of the TM or ADEM. However, concern remains among the TM and ADEM community that vaccines could be responsible for triggering autoimmune demyelinating events like TM or ADEM.

The researchers in this study used the Vaccine Safety Datalink (VSD) to analyze 64 million vaccine doses over the period of January 1, 2007 to December 31, 2012. The VSD is a collection of data from participating healthcare systems across the United States in collaboration with the Centers for Disease Control and Prevention’s Immunization Safety Office. This automated database includes immunization registries, and collects information on more than 9 million patients per year. The study population for this research consisted of all children and adults of any age who received one or more vaccines during the study period, and were enrolled in health plans at six VSD sites.

First-ever TM and ADEM diagnoses were identified using each VSD site’s internal electronic medical record, and the cases required at least one diagnosis by a neurologist within 3 months of initial diagnosis. The researchers did not include individuals with a history of Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorders. The cases were first reviewed by trained medical records analysts and then reviewed by a neurologist with expertise in demyelinating illnesses to ensure the cases met research criteria. The study utilized the database to match a comparison group to each case based on type of vaccination, age, sex, VSD site, and whether their vaccination occurred during the exposure intervals, which were chosen by the researchers based on prior studies and expert opinion. The two exposure periods analyzed were: (1) 5-28 days from vaccination as the most likely interval to result in a demyelinating event; and (2) 2-48 days from vaccination to the demyelinating event to ensure an increased risk was not missed. The comparison interval that the researchers chose was 43 days through nine months prior to the demyelinating event to avoid duplicate influenza vaccines over two seasons.

The researchers looked at whether or not each case received a vaccine during the exposure interval or the comparison interval before the demyelinating event occurred. They then compared this to the proportion of the entire study population that received a vaccination during the exposure interval before the demyelinating event date. Eighty-one cases of TM and fifty-six cases of ADEM were included. The researchers found that for TM, there was not a statistically significant increased risk of a demyelinating event in either the 5-28 day exposure interval or the 2-48 day exposure interval after receiving any vaccination. The researchers also found that for ADEM, only the Tdap vaccine had a statistically significant association with an increased risk of a demyelinating event. This was only found in the 5-28 day exposure interval. The Tdap vaccine is used for adolescent and adult tetanus, reduced diphtheria, and acellular pertussis. However, the authors noted that there are some concerns with the validity of this outcome. For example, there were only two cases of ADEM that occurred during this time period, which is a very small number, and if there had only been one case, this finding would not have been statistically significant. Also, the authors wrote that they did many statistical tests and did not adjust for this, so they stated that the results could be due to chance. Furthermore, the authors noted that even if we accept an increased risk for ADEM after the Tdap vaccine, the extra risk is very small and not likely to be more than 1.16 cases of ADEM per million doses of the Tdap vaccine. Dr. Benjamin Greenberg from the University of Texas Southwestern Medical Center also noted the study does not reveal the six clinical centers used to collect cases. If these centers were referral centers they may have an overrepresentation of TM and ADEM cases – thus overestimating the risk.

Overall, the authors stated that the results of this study conclude that vaccinations mostly do not have a statistically significant association with demyelinating events that occur in TM and ADEM.  They also noted that one limitation of the study was that they chose the exposure interval, so if the interval was chosen incorrectly, an increased risk might have been missed. Also, they stated they did not review combinations of vaccines but rather analyzed each vaccine’s risk separately. Finally, the researchers stated that they purposefully did not adjust for multiple observations so that they could achieve higher sensitivity in their results; nonetheless, they noted that they only identified one statistically significant result (the Tdap vaccine). Despite its limitations, the authors noted the study’s strength was its review of all TM and ADEM cases by medical records analysts and a neurologist, which likely limited misclassification of cases with these disorders, which reduces bias and makes results more likely to be accurate. According to the authors “In conclusion, TM and ADEM are rarely, if ever, associated with vaccines.”

Think people should hear about this?

Genetic Mutation Found in Familial Transverse Myelitis

By Dr. Michael Levy

Associate Professor of Neurology at the Johns Hopkins Hospital and Medical Director of General Neurology at the Johns Hopkins Hospital in Baltimore, MD

We found a rare genetic mutation in some families of patients with acute transverse myelitis (TM) that may provide new insights into the disease process. Two sisters with TM came to our attention through the TMA who agreed to donate their DNA for a thorough genetic analysis called exome sequencing. Only one meaningful difference was found in both sisters, which their two healthy brothers did not have: a mutation in a gene called VPS37A. As it turns out, a genetic mutation like theirs is extraordinarily rare in nature. No other known organism in the animal kingdom has this mutation so we thought this could be biologically important. But we didn’t know how common this was. With the help of the TMA, the Accelerated Cure Project and collaborators at Johns Hopkins, we screened an additional 86 TM patients and found another patient with the same rare mutation! It is statistically beyond coincidence to find three human beings with this same rare genetic mutation unless it has something to do with the rare disease they all share, TM. We do not yet understand how this gene, or the genetic mutation, is associated with TM. But with the continued support of the TMA, funding agencies and of course, our TM patients, we are beginning to piece this puzzle together.

The abstract below was presented at American Academy of Neurology 2017 in Boston, MA.

Maureen Mealy¹, RN, Tai-Seung Nam², MD, PhD, Santiago Pardo¹, Carlos A. Pardo¹, MD, PhD, David Valle³, MD, Kathleen Burns³,⁴, MD, PhD, Michael Levy¹, MD, PhD

1.     Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

2.     Department of Neurology, Chonnam National University Medical School, Gwangju, South Korea

3.     Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA

4.     Department of Pathology, Johns Hopkins University, Baltimore, MD, USA

Background. Idiopathic transverse myelitis is an acute inflammatory attack of the spinal cord leading to weakness, sensory loss and bowel/bladder dysfunction. The prevalence is 0.1-0.2/100,000 and there are no known risk factors.

Objective. To identify a genetic risk for development of idiopathic transverse myelitis.

Methods. We identified two sisters who both have idiopathic transverse myelitis, and compared exome sequencing on DNA samples from them with two healthy siblings. We also sequenced 200 additional samples from patients with idiopathic transverse myelitis, multiple sclerosis, neuromyelitis optica, other neurological conditions and healthy controls.

Results. The two sisters with idiopathic transverse myelitis both had acute onset of sensory loss in the legs, followed by weakness and bowel/bladder dysfunction. The first sister developed myelitis at age 15 with clinical nadir of complete paralysis. Over the next few years, she recovered her ability to walk without assistance. Recent MRI demonstrated persistent T2 lesion in the lower thoracic cord. The second sister developed myelitis at age 50 with nadir of complete sensory loss from T6 down and paraparesis in the legs, associated with an MRI lesion at T6. She also made a partial recovery with treatment. Both sisters share a non-synonymous homozygous mutation in only one gene, VPS37A (c.700C>A, p.Leu234Ile) in the whole genome analyses. One healthy sibling was heterozygous for this mutation. We screened an additional 261 samples from patients with ITM and neuroimmunological diseases by Sanger sequencing of this portion of VPS37A and identified another idiopathic TM patient with this same rare homozygous mutation. No patients with multiple sclerosis, neuromyelitis optica, other neurological conditions or healthy controls contained a homozygous mutation in VPS37A.

Conclusions. A mutation in VPS37A may predispose to development of idiopathic transverse myelitis. Further studies are necessary to determine the frequency of this mutation in this patient population and how this genetic mutation might contribute to risk of disease.

Think people should hear about this?

Acute Disseminated Encephalomyelitis (ADEM): Past, Present, and Future

Cynthia Wang, MD

James T. Lubin Fellow at the University of Texas Southwestern Medical Center in Dallas

Acute disseminated encephalomyelitis (ADEM) is a rare, autoimmune neurological condition that often occurs in young children following an infection. Initial symptoms of ADEM may be quite variable and non-specific, including headache, fever, irritability, confusion, sleepiness, and weakness. Over the years, our understanding of ADEM has matured, though many aspects of the condition remain mysterious. What leads some individuals to develop the condition in the first place? Could it happen again? Why do some individuals make a full recovery while others have lasting impairment?

ADEM is thought to develop when the body mounts a response to an infection, but rather than solely attacking the invading organism, it mistakenly targets parts of the nervous system as well. ADEM is primarily a clinical diagnosis, meaning that we do not have a perfect test that can tell us definitively whether a child or adult has ADEM. Laboratory studies of blood and spinal fluid, and MRIs of the brain and spine can help rule out other conditions and support the diagnosis of ADEM. If ADEM is suspected, children and adults often receive steroid medications during their hospitalization to help reduce inflammation and suppress the body’s confused immune system.

For the vast majority of those affected by ADEM, it is a one-time illness and does not recur. Many children make excellent recoveries and largely seem to return to normal. However, episodes of new neurological symptoms, especially those that develop 3 months or more after the initial event, raise concern for an alternate diagnosis, such as multiple sclerosis or neuromyelitis optica spectrum disorder. In our clinic at UTSW Dallas, our practice has been to repeat MRI brain scans at 3-4 months after ADEM to establish a baseline for future comparison. Any new clinical events or MRI brain lesions occurring after this period of time would lead to scrutiny of the ADEM diagnosis

Another practice in our clinic is to perform neuropsychological testing on our patients who have had ADEM. Increasing research highlights that children with ADEM may have subtle cognitive deficits involving processing speed, visual-motor integration, executive functioning, language processing, and behavioral regulation that may not be evident until they get older and are faced with increasing academic and social demands. Neuropsychological testing is geared toward uncovering areas of weakness and may be helpful in guiding school accommodations for children affected by ADEM.

We are just beginning to study the long-term outcomes of children with ADEM, particularly their cognitive potential, academic achievement, social functioning, and quality of life. In the past couple of years, we have also learned more about a subset of ADEM patients who make antibodies toward a protein on the outer surface of certain cells called myelin oligodendrocyte glycoprotein (MOG). Over time, our ability to test for this antibody has improved, along with increasing understanding that this group of MOG positive ADEM patients may have similarities in their clinical presentation, neuroimaging, and prognoses that may impact their care.

 

Introducing APERTURE: Assessment of Pediatric and Adult Encephalomyelitis Related Outcomes: Understand, Reveal, Educate

To help address gaps in our understanding about ADEM, our group at University of Texas Southwestern Medical Center will be conducting a study examining the long-term outcomes of individuals with ADEM. We aim to collect data on a large group of children and adults diagnosed with ADEM and review their presenting history, laboratory studies, neuroimaging, treatment course, and recovery from ADEM. Individuals between ages 0-64 with the initial diagnosis of ADEM are welcome to participate. People who cannot travel to our center in Dallas can participate remotely by providing medical records, MRI studies, completing questionnaires, and in some cases, neuropsychological testing. Enrollment will begin in June 2017.

We are eager to learn more about this rare neurological condition, and with your help, work toward improving our ability to better care for those affected by ADEM.

Please email PEDICONQUER@UTSouthwestern.edu for more details.

Think people should hear about this?

Currently Enrolling NMOSD Clinical Trials

Conducting research through clinical trials is one of the ways we develop and identify new therapies and learn what the best treatments are for rare neuro-immune disorders. There are three clinical trials that are currently enrolling patients with neuromyelitis optica spectrum disorder (NMOSD). We have included a summary of all three studies below. For more information on clinical trials, visit http://bit.ly/tma-clinical-trials.

PREVENT Study

Alexion Pharmaceuticals, Inc. is conducting a clinical trial called the PREVENT Study. The primary objective of the study is to assess the efficacy and safety of an investigational medicine as a potential treatment to prevent relapses in NMO and NMO Spectrum Disorder (NMOSD).

This is a randomized double blind study, where participants will receive investigational medication or placebo and neither the participant nor the study doctor or their staff will know who received the drug or placebo. In this study, 2 out of 3 participants will receive investigational medication and 1 out of 3 participants will receive placebo. The medication is given intravenously at the study doctor’s office or infusion center.

Participants may be eligible if they are at least 18 years old, have a positive test for the NMO-IgG antibody and have experienced 2 relapses in the past 12 months or 3 relapses in the last 24 months with at least 1 relapse in the last 12 months.

This is an “add on study,” and patients may be able to continue taking their current NMO or NMOSD medications and receive the study medication.

There are known and unknown potential side effects, which will be discussed prior to enrollment and detailed in the informed consent. For more information, email: clinicaltrials@alxn.com

N-Momentum Study

Medimmune is currently conducting the N-Momentum study, a clinical research trial in subjects with NMOSD. The trial is actively recruiting seropositive and seronegative NMOSD patients around the world. The main objective of this study is to determine if inebilizumab (formally known as MEDI-551) compared to placebo can significantly delay the time it takes for a new NMO/NMOSD attack to occur.  The trial will recruit 252 NMOSD subjects from approximately 100 sites in 25 countries, 67 confirmed adjudicated NMOSD attacks are needed to determine if inebilizumab is effective compare to placebo.

This is a multinational randomized, double-masked, placebo-controlled study with an open‑label period. Eligible NMO/NMOSD patients will be “randomized” in a 3:1 ratio to received either MEDI-551 or placebo. This random selection will give a 25% (1 in 4) chance of getting placebo and a 75% (3 in 4) chance of getting Inebilizumab.

This trial enrolls seronegative and seropositive NMOSD patients. After being enrolled in the study, subjects are followed for 28 weeks in the placebo-controlled treatment period where inebilizumab or placebo will be given by an intravenous infusion on Day 1 and Day 15. During the study, no additional immunosuppressive therapy will be allowed.

Patients will have the option to enroll into the open-label period if a confirmed NMOSD attack occurred during the placebo-controlled treatment period. Subjects who complete the placebo-controlled treatment period without experiencing an attack will also be given the option to enroll in the open-label period. During the open-label period, inebilizumab will be given on Day 1 and Day 15 and then every 6 months thereafter until the end of the study.

As of April of 2017, 141 NMOSD subjects have been enrolled in the study of which 130 are AQP4 seropositives and 11 are AQP4 seronegatives.

If you are interested in participating, please contact: the AstraZeneca Clinical Study Information Center at 1-877-240-9479 or email information.center@astrazeneca.com

SA237 Study

This research is being conducted to evaluate the efficacy, safety, pharmacodynamic, pharmacokinetic and immunogenic profiles of a humanized anti-human IL-6R neutralizing monoclonal antibody (SA237) in patients with Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD). This study is being conducted in the US and Canada and will enroll seventy (70) patients to participate in this research.

SA237 is a humanized anti-human IL-6R neutralizing monoclonal antibody that was designed by applying recycling antibody technology to the approved anti-IL6 receptor antibody, tocilizumab, which is currently marketed as a treatment for rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis and Castleman’s disease. The recycling antibody technology enabled SA237 to bind to IL-6 receptor multiple times and be slowly cleared from plasma, which is expected to contribute to improvement and is convenient with once monthly dosing frequency. The longer plasma half-life of SA237 compared with tocilizumab was confirmed based on the results of a non-clinical study and a Phase 1 study in healthy volunteers.

Individuals who have NMO or NMOSD and are between the ages of 18 and 74 years may be eligible.

If you are interested in participating, please email sa237@chugai-pharm.co.jp

Think people should hear about this?

Queen’s University researchers make major myelin repair discovery

Queen’s University Belfast scientists have discovered that specific cells from the immune system are key players in repairing myelin in the central nervous system – a fundamental breakthrough that could revolutionize the treatment of debilitating neurological disorders such as multiple sclerosis (MS) and many demyelinating conditions such as transverse myelitis, neuromyelitis optica spectrum disorder and acute disseminated encephalomyelitis. In all these conditions, the myelin is damaged, and there are immune cells present at many sites of damage in the central nervous system. Myelin is important because without it, nerves are not able to conduct or send signals where they need to go.

The research study, led by Dr Yvonne Dombrowski and Dr Denise Fitzgerald at the Wellcome Wolfson Institute for Experimental Medicine at Queen’s University Belfast, is being hailed as a landmark study in unravelling the mysteries of how the brain repairs damage.

The research breakthrough, which was published in Nature Neuroscience, shows that a growth regulatory protein made by certain cells within the immune system, called regulatory T cells (Treg), triggers the brain’s stem cells to mature into oligodendrocytes, which are cells that repair myelin. What the Fitzgerald group and collaborators have discovered in different settings of myelin damage (including spinal cord and brain tissue), is that this specific immune cell, Treg, is critical for driving efficient repair of myelin. The Tregs accomplish this by producing a protein, CCN3, that triggers immature oligodendrocytes to mature, start producing myelin, and re-wrap nerves.

They studied this using a focal demyelinating mouse model induced by injecting lysolecithin into spinal cord white matter. They confirmed their findings with a second demyelinating model at a different central nervous system site using another drug called cuprizone. Further, in brain slice cultures, they were able to show that Tregs promoted brain tissue myelination and remyelination in the absence of inflammation. The discovery means that researchers can now use this new knowledge to develop medicines which will boost these particular cells and develop an entirely new class of treatments for the future.

Senior author of the study, Dr Denise Fitzgerald from Queen’s, was diagnosed with transverse myelitis when she was 21 and had to learn to walk again. Commenting on the findings, Dr Fitzgerald said: “This pioneering research, led by our team at Queen’s, is an exciting collaboration of top scientists from different disciplines at Cambridge, San Francisco, Edinburgh and Nice. It is by bringing together these experts from immunology, neuroscience and stem cell biology that we have been able to make this landmark discovery. This is an important step forward in understanding how the brain and spinal cord are naturally repaired and opens up new therapeutic potential for myelin regeneration in patients. We continue to work together to advance knowledge and push the boundaries of scientific knowledge for the benefits of patients and society, in a bid to change lives for the better, across the globe.”

Original Research: Dombrowski Y, O’Hagan T, Dittmer M et al. Regulatory T cells promote myelin regeneration in the central nervous system. Nat Neurosci. 2017 Mar 13.

Think people should hear about this?