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Cure JM Currently Funded Research and Programs

VIEW A COMPLETE LIST OF PUBLISHED RESEARCH STUDIES SUPPORTED BY CURE JM FOUNDATION

Novel MSA Biomarkers in Juvenile Myositis

Sarah Tansley, PhD, MRCP (Rheum), Bath University UK

Juvenile Myositis is an incredibly variable disease ranging from milder disease that responds to standard medications to severe disease which causes damage despite aggressive treatment. Myositis autoantibodies (MSA) are markers present in the blood of myositis patients. More than ten different MSA have been identified in JM patients and each is a marker for a different subgroup. MSA highlight those patients at greatest risk of chronic disease, treatment resistance and important complications such as lung involvement, ulcers and calcinosis. MSA can be identified in approximately 60% of JM patients who benefit from this additional information to plan treatment and further tests. MSA are likely to be important in developing a personalized approach to treatment in JM. The ability to target existing and novel treatments to those patients most likely to benefit will enable more rapid disease control and reduced side-effects.

This new grant at Bath UK focuses on the often forgotten 40% of JM patients labelled as ‘MSA negative’. Preliminary data from the Bath group suggest that these patients are not in fact all the same, and that yet to be discovered MSA markers are present in this group.

Using blood samples already collected from a large UK JM study of over 500 patients specially adapted MSA detection methods will be deployed to identify ‘new’ MSA in this group. Critically both the characteristics of patients JM diagnostic presentation and any new MSA will be fully documented, expanding the personalized medicine approach for this cohort of JM patients.

T cell differentiation and T-reg/Th17 balance in a myosin-induced mouse model of experimental autoimmune myositis

Sara Sabbagh, DO, Medical College of Wisconsin

JDM is characterized by the body's immune system attacking own muscle tissues, which results in inflammation and weakness. Many different types of immune cells contribute to this process, but what drives the formation of these different cell types is unknown. Certain subpopulations of immune cells: T-helper 17 cells (Th17) and T-regulatory cells (Treg) are thought to contribute to the development of JDM. Both the amount of inflammation and the relative population of other immune cells can affect the number of Th17 and Treg cells. Modelling these differences and how they affect the relative proportions of Tref and TH17 cells is potentially pivotal in understanding the course of JDM. Here we propose that dysregulation. The group led by Dr. Sabbagh aims to generate a mouse model of myositis investigating the effect different populations of immune T cells have on the relative populations of TH17 and Treg cells.

Using mice as a model for human muscle disease is a useful tool as the observed disease course and muscle tissue alterations are similar to human disease. The benefits of using a mouse model also include the ability to investigate genes of interest in specific cell types and to trial different therapies in the model.

Interferon Scores in Juvenile Dermatomyositis and Correlation with Disease Activity

Jayne MacMahon, PhD, SickKids, Toronto, Canada

Juvenile Dermatomyositis is a potentially damaging autoimmune disease. Even with treatment, 60% of patients will have ongoing disease activity. This leads to complications that impact day to day life. Predicting which patients are at risk can be challenging. This leads to patients being undertreated and other patients being overtreated.

A marker, called ‘interferon’ has been found in the blood of patients with JDM. This seems to be an important marker in the trajectory of JDM. A scoring system based on this marker has been developed. Initial work in Toronto has indicated that this interferon score is linked to disease activity in patients with JDM. To prove this the Toronto group will investigate the interferon score in blood samples from patients with JDM.

A comparison of the results of the interferon score to the disease activity levels at the time the sample was taken will be used to refine a correlative mode. Highly detailed information on disease activity at each clinical visit. De. MacMahon's group plans to prove that the interferon score and disease activity are linked. The ultimate goal is in the future, this score model could be used to predict which patients are likely to have ongoing disease activity. This will help to guide treatment and prevent complications. Ultimately, Dr. MacMahon wants to publish the interferon score algorithm and have it utilized to improve long term outcomes for all children with JDM.

The Effect of Exercise, Creatine, and Coenzyme Q10 Supplementation on Muscle Function in Children with Myositis

Brian Feldman, MD, M.Sc., FRCPC

A key aspect of Juvenile Dermatomyositis is muscle weakness. The level of weakness can vary and there is some evidence that exercise can aid recovery of muscle strength. In studies of children with a variety of chronic diseases, supplementation of oral creatine (Cr) and coenzyme Q10 (CoQ10) have been shown to improve energy metabolism in the muscle and to improve muscle function. In myositis specifically, supplementation of Cr combined with exercise improved muscle function in adults. In children, Cr supplementation has conflicting results and has not been combined with exercise. To date, CoQ10 has not yet been used as a therapeutic supplement for myositis.

The primary aim of Feldman’s study is to determine whether supplementation of Cr and CoQ10, combined with an exercise program, can improve muscle function in children with JDM. The secondary aims of this study are to determine if this intervention can improve disease activity and quality of life. In order to accurately quantify the effect of this supplement and exercise regimen, the primary outcome measure will be muscle function as measured by the Wingate Anaerobic Test; secondary outcome measures will include measures of aerobic fitness, muscle strength, disease activity, and quality of life. Patients between the ages of 8 to 18 years with JDM will be recruited from the rheumatology clinic at the Hospital for Sick Children in Toronto, Canada. They will complete a pre-baseline assessment of exercise measures and will be started on Cr and an exercise program for two weeks before entering a prospective, randomized, placebo-controlled, multiple baseline trial for CoQ10 supplement treatment.

Dr. FeldmanThe Effect of Exercise, Creatine, and Coenzyme Q10 Supplementation on Muscle Function in Children with Myositis

Brian Feldman, MD, M.Sc., FRCPC

A key aspect of Juvenile Dermatomyositis is muscle weakness. The level of weakness can vary and there is some evidence that exercise can aid recovery of muscle strength. In studies of children with a variety of chronic diseases, supplementation of oral creatine (Cr) and coenzyme Q10 (CoQ10) have been shown to improve energy metabolism in the muscle and to improve muscle function. In myositis specifically, supplementation of Cr combined with exercise improved muscle function in adults. In children, Cr supplementation has conflicting results and has not been combined with exercise. To date, CoQ10 has not yet been used as a therapeutic supplement for myositis.

The primary aim of Feldman’s study is to determine whether supplementation of Cr and CoQ10, combined with an exercise program, can improve muscle function in children with JDM. The secondary aims of this study are to determine if this intervention can improve disease activity and quality of life. In order to accurately quantify the effect of this supplement and exercise regimen, the primary outcome measure will be muscle function as measured by the Wingate Anaerobic Test; secondary outcome measures will include measures of aerobic fitness, muscle strength, disease activity, and quality of life. Patients between the ages of 8 to 18 years with JDM will be recruited from the rheumatology clinic at the Hospital for Sick Children in Toronto, Canada. They will complete a pre-baseline assessment of exercise measures and will be started on Cr and an exercise program for two weeks before entering a prospective, randomized, placebo-controlled, multiple baseline trial for CoQ10 supplement treatment.

Multi-Center JM Patient Registry

Cure JM has partnered with the Childhood Arthritis and Rheumatology Research Alliance (CARRA), a group of 500 North American pediatric rheumatologists, researchers, and other health care professionals, to launch a multi-center JM patient registry. The CARRA JM patient registry is a database that collects information at the time of diagnosis and at regular intervals about how a patient is doing, medications used, and side effects. Pooling all this information lets CARRA researchers do larger studies that will ultimately help JM families make more informed decisions on treatment options. This Cure JM supported CARRA JM patient registry went live in December 2017 at 18 CARRA sites, with expansion planned to a total of 75 sites in 2018.

Dr. NagarajuReveragen Partnership To Pursue Vamorolone As Potential Juvenile Myositis Treatment

Kanneboyina Nagaraju, DVM, MVSc, PhD.

Cure JM has engaged in a new strategic partnership with ReveraGen, a clinical-stage drug development company with a focus on developing new anti-inflammatory therapeutics. In pre-clinical and clinical trials for other chronic inflammatory states, vamorolone has been well tolerated without the side effects of prednisone or other corticosteroids. Vamorolone works by replicating the good, anti-inflammatory effects of steroids without the side effects by modifying the chemistry of the drug. Specifically, the aspect of corticosteroids where many genes are turned on is removed in vamorolone. This gene activity is responsible for the majority of side effects in steroids. Vamorolone is in phase II clinical trials in pediatric Duchene Muscular Dystrophy, and is on the "fast track" approval process within the FDA. The goal of Cure JM’s engagement with ReveraGen is to conduct the preliminary studies necessary to add JM as a targeted indication for vamorolone in future clinical trials.

Dr. Jim IngleseNCATS Drug Development Program

Jim Inglese, Ph.D.
Principal Investigator, Division of Pre-Clinical Innovation at National Center for Advancing Translational Sciences (NCATS), National Institutes of Health

Cure JM has invested in a 3-year drug development program at NCATS led by Jim Inglese, Ph.D. Cure JM’s funding supports the team’s efforts to screen hundreds of thousands of new drugs, as well as existing drugs currently used in the treatment of other diseases, to determine their possible usage in the treatment of JM. They will then perform follow-up studies on the most promising drugs, with a goal of developing a short list of new and re-purposed drugs that have the potential to improve the prognosis for JM patients.

Dr. HakonarsonCenter for Applied Genomics (CAG) at Children’s Hospital of Philadelphia (CHoP)

Hakon Hakonarson, PhD, MD and Charlly Kao, PhD

Cure JM has invested in a genetic discovery program at the Center for Applied Genomics (CAG) at Children’s Hospital of Philadelphia (CHoP). With their state-of-the-art facility and biobank, the Center for Applied Genomics aims to identify the genetics that play a part in Juvenile Dermatomyositis. The goal is as we find specific genes that regulate autoimmunity in JM and better understand what genetic mutations are at work in those genes, we can find drug interventions to modify genetic behavior.

Jessica Neely, M.D.Understanding Heterogeneity in Pediatric Rheumatic Diseases to Inform Precision Medicine Approaches to JDM

Jessica Neely, M.D.
Clinical Fellow, University of California, San Francisco, Benioff Children’s Hospital

Dr. Neely is using a computational approach to identify biomarkers by leveraging existing data to identify transcriptional signatures common among patients with JDM. She is also using a novel sequencing technology that allows examination of gene expression on the individual cell level. This technology holds great promise in identifying new biomarkers for children with JDM and will help us learn more about the cause of disease.

Zoe BetteridgeValidate Commercial Testing Labs to better enable these labs to conduct myositis-specific autoantibody testing

Zoe Betteridge, Ph.D.
University of Bath, United Kingdom

Currently, there are few labs in the U.S. or Europe whose work in autoantibody testing meets a "gold standard" for accuracy and breadth (testing for all known myositis auto antibodies). Dr. Betteridge’s project will test and validate commercially available kits for myositis antibodies, potentially increasing the number of lab sites and lowering costs.

Dr. Laura TasanUltrasound as a Diagnostic Tool

Laura Tasan, M.D.
University of Pittsburgh

Dr. Tasan will study the feasibility of Ultrasound as a diagnostic tool for muscle disease in children. If successful, Ultrasound could supplement or replace the use of costlier MRIs to monitor disease activity in JM.

Josh WoolstenhulmeUnderstand the Etiology of Fatigue and Fatigability in JDM using Cardiorespiratory Measures

Josh Woolstenhulme, D.P.T., Ph.D.
George Washington University

The project will measure oxidative stress and mitochondrial function as possible causes of fatigue. This is an important study for patients and families of those with JDM, as it is a common question as to why a patient with JDM continues to feel significant fatigue despite disease control.

Dr. Paul NormanNovel Genomics Study in Juvenile Dermatomyositis

Paul J. Norman, Ph.D.
Senior Research Scientist, Department of Structural Biology, Stanford School of Medicine

Dr. Norman is investigating the entire HLA genomic region using a new and powerful method he developed that will shed new light on the genetics of JM. Previously uncharacterized genes may interact with HLA genes to become risk factors for disease. Proper understanding of these risk factors opens the door for new diagnostic indicators, treatment targets and, in the long-term, prevention of the disease through directed gene-therapy approaches.

Dr.Rebecca NicolaiInterferons in Juvenile Dermatomyositis: Pathogenic Role and Correlations with Disease Characteristics at Onset and Long-Term Course

Rebecca Nicolai, M.D.
Division of Rheumatology, Bambino Gesu Hospital, Rome, Italy

Dr. Nicolai aims to measure type I and type II interferon gene expression in JDM muscle, potentially leading to the discovery of additional biomarkers to measure disease activity. This is important because the pathogenesis of JDM is not understood, although it is likely that aberrant interferon expression plays a major role. If so, this could open up the possibility for new drug treatments that inhibit interferon expression in JM.

Dr.Takayuki KishiHeterogeneity of Juvenile Myositis, with a Focus on Therapies and Responses

Takayuki Kishi, M.D., Ph.D.
Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health

Dr. Kishi’s goal is to investigate clinical response to therapies in patients with JDM from a large JM registry. He will examine the impact of initial medications and other factors on achievement of inactive disease, complete clinical response, and remission. He will also compare different treatment regimens and examine differences in their response rates. These analyses should provide new information on response rates to therapies and predictors of responses to therapies in JDM.

Dr. Emily BrunnerPhysical Activity Monitors as Outcome Measures in Juvenile Myositis

Emily Brunner, D.O.
Pediatric and Adult Rheumatology Fellow, University of Pittsburgh Medical Center, Division of Rheumatology and Immunology

In this pilot study, Dr. Brunner is evaluating the use of Personal Activity Monitors (Fitbits) as a validated measurement tool for physical activity and strength measurement among JM patients. This easy to use tool could be used as a supplement to existing scoring measures and could provide better outcome measurement of a patient’s physical function and response to treatment.

Dr. Kaveh ArdalanValidation of Patient Reported Outcomes Measurement Information System (PROMIS) in Juvenile Myositis

Kaveh Ardalan, M.D., M.S.
Attending Physician, Division of Rheumatology, Ann & Robert H. Lurie Children’s Hospital of Chicago; Instructor of Pediatrics and Medical Social Sciences, Northwestern University Feinberg School of Medicine

Dr. Ardalan’s study aims to validate the use of PROMIS (Patient Reported Outcomes Measurement Information System) to improve Quality of Life data collection. This long-term longitudinal data is needed to assess emotional distress, pain, fatigue, and physical function allowing clinicians to better target interventions —pharmacologic, exercise-related, or psychological. This information would enable JM patients who are struggling with disease management to be more easily identified for intervention.

Dr. Jeffrey DvergstenThe Use of Metabolomics to Develop Novel Biomarkers for Juvenile Dermatomyositis

Jeffrey A. Dvergsten, M.D.
Assistant Professor of Pediatrics, Duke University School of Medicine

Dr. Dvergsten aims to identify aberrant patterns of metabolite expression in blood and muscle of children with JDM to develop new biomarkers for help in diagnosis, assessment of disease activity and response to treatment in JM.

Dr. Hanna KimNovel Biomarkers associated with Disease Activity in JDM

Hanna Kim M.D.
Fellow, Division of Pediatric Rheumatology Children’s National Medical Center and National Institutes of Health

In order to expand biomarker analysis to broad proteomic analysis, she is replacing cytokine analysis from her previous grant. The new SomaLogic platform will replace the previously proposed platform called Luminex and is much more likely to successfully identify a new biomarker in JDM without requiring more blood samples.

Dr. Claire DeakinGenetic Risk Factors in Juvenile Dermatomyositis

Claire Deakin, Ph.D.
Post-Doctoral Fellow at University College, London

This grant which will enable inclusion of North American samples to enhance the statistical power of her study. The project will study genetic risk factors for JDM using samples from a large number of North American and UK patients with JDM. By studying large numbers of patients, this project may also be able to study genetic risk factors for developing specific features, such as the formation of calcium deposits. It will also help us find out whether the age patients are when they get disease influences the role of genetic differences in JDM or its subgroups. The biological effect of these genetic differences will also be studied in order to help us understand the cause of disease better. This research may lead to more information about the causes of JDM and why certain patients develop certain features.

Dr. James JarvisPlasma Exosomes in Juvenile Dermatomyositis

James Jarvis M.D.
Professor of Pediatrics from the University of Buffalo, NY

JDM is a disease with extensive inflammation in blood vessels. Exosomes are found in considerable numbers in the circulation, and are a means through which cells communicate with one another Dr. Jarvis is trying to understand how blood vessels become injured in JDM, as he thinks it’s how the muscle injury starts. He will culture exosomes from children with JDM with blood vessel cells and determine how the small RNA molecules disturb the regulation of genes in the blood vessel cells. By comparing what is seen with JDM exosomes to the exosomes of healthy children, we will have new ways to understand how blood vessels are injured in JDM.

Dr. Chack-Yung YuComplement C4 in Disease Risk and Pathogenesis of Juvenile Dermatomyositis

Chack-Yung Yu, D.Phil.
Professor of Pediatrics; Professor of Molecular Virology, Immunology and Medical Genetics, Center for Molecular and Human Genetics, The Research Institute at Nationwide Children’s Hospital and The Ohio State University, Columbus, OH

This study will analyze whether variations of C4A genes and changes of C4 proteins can be used to reveal the severity of JDM and how the illness may develop. The research team will analyze hundreds of DNA samples from JDM patients and healthy subjects. They will use cutting-edge techniques to perform experiments -some of the techniques were originally designed by this research team, who are pioneers in the research field of immune genetics. They hope, through their research, to be able to develop better and more specific ways to diagnose and treat the disease, and hopefully to find a cure in the future.

Dr. Megan CurranPhysician Education Program

Megan Curran, M.D.
Attending Physician, Division of Rheumatology, Ann & Robert H. Lurie Children’s Hospital of Chicago; Assistant Professor, Northwestern University Feinberg School of Medicine; Program Director, Northwestern/McGaw Pediatric Rheumatology Fellowship Program

Cure JM Foundation funded a multi-stage project to educate physicians about JM across North America. The goal is to help physicians diagnose JM faster so that patients can begin treatment without delay. The first part of this project was a survey of 400 JM families to better understand the patients’ symptoms and path to diagnosis. The second part of this project was an E-newsletter sent to 10,000 pediatricians to help educate them about the signs and symptoms of JM so they can make an accurate and timely diagnosis. The pediatricians receive CME credit (Continuing Medical Education) for reading it and taking a short test afterwards. CME credits are required in most states for physicians to keep their medical licenses. The next stage of this project will be developing and delivering materials to pediatricians with images of the primary signs/symptoms of JM.

Dr. Hanna KimNovel Biomarkers Associated with Disease Activity in JDM

Hanna Kim, M.D.
Fellow, Division of Pediatric Rheumatology Children’s National Medical Center and National Institutes of Health

This study will compare and contrast serum markers and gene expression patterns in JDM with those of other closely related disorders (CANDLE and SAVI) with the hopes of better understanding the cause(s) of JDM and possible treatments. The study also intends to identify dysregulated pathways in JDM using RNA-Sequencing to improve biomarkers related to disease activity. By developing a better biomarker, the research team hopes to better predict who will respond to a particular therapy, indicate when to stop and start therapy and develop more JDM-specific therapies in the future.

Dr. Ann ReedPredictive Model of Disease Outcomes using Computational Biology Modeling in Children with Inflammatory Muscle Disease

Ann M. Reed, M.D.
Chair of the Department of Pediatrics, Duke University School of Medicine

Research study at the Mayo Clinic to determine associations between disease outcomes and various features of JDM, which may lead to the prediction of which patients would benefit from particular treatment choices.

Dr. Susan KimLymphocyte Repertoire in Juvenile Dermatomyositis

Susan Kim, M.D., MMSc
Pediatric Rheumatologist and Assistant in Medicine at Boston Children’s Hospital, Harvard University in Boston, MA

Research study at Boston Children’s Hospital using "next generation sequencing" to study detailed T & B cell differences in JDM. This should lead to a better understanding of changes in the immune system, which may help to advance the understanding of JDM and improve future outcomes.

Dr. Dawn WaheziPremature Atherosclerosis in Juvenile Dermatomyositis

Dawn Wahezi, M.D.
Physician, Assistant Professor, Pediatric Rheumatology, Children’s Hospital at Montefiore

Research study at Children’s Hospital at Montefiore that aims to identify which risk factors may be the most significant indicators of early heart disease in children with JDM.

Dr. Anne StevensSimultaneous Genomics and Microbiotica Phenotyping in Juvenile Dermatomyositis (JDM)

Anne Stevens, MD, Ph.D.
Seattle Children’s Research Institute

Long Term Aim: To identify specific oral and fecal microbial communities in JDM that may be targeted in future therapeutic trials. The influences of susceptibility genotypes for known immune function genes and dietary elements known to alter the microbiome will be characterized to provide the rationale for future diagnostic and therapeutic trials.

Cure JM Program of Excellence in Juvenile Myositis  Research at Stanley Manne Children’s Research Institute of Ann & Robert H. Lurie Children’s Hospital of Chicago

Dr. Lauren Pachman, the Principle Investigator and Director, has cared for over 550 children with JDM and other forms of inflammatory myopathy. Dr. Pachman has patients who travel from around the country to see her for a diagnosis and/or treatment.  She is also called upon for consults and referrals from other doctors.  Her team is working to discover the biomarkers of JM activity to guide the utilization and/or creation of more effective therapies. They have already identified a variety of genetic and environmental factors that not only play a role in the onset of symptoms, but also govern the child’s outcome.

George Washington University Myositis Center

Multidisciplinary effort made possible by a grant from Cure JM Foundation. As a national referral site for inflammatory muscle diseases, the Center is often called upon to either establish a diagnosis or to provide a second opinion related to the management of children and adults with JM. Working in collaboration with the NIH, the Center also specializes in JM research and education.

International Consensus Conference 

Myositis researchers from around the world came together to develop standard measures of “improvement” for myositis patients. These new measures are critical for research, as they will be the end goals for future myositis clinical trials. Plus, this should help facilitate future drug development for JM.

Genetic Risk Factors for Calcinosis   

Research study at Stanford University utilizing previously collected blood samples to look at certain genes and potentially determine their role in the development of calcinosis

Gastrointestinal Bacterial Tract in JM Patients 

Pilot study at Seattle Children’s Hospital to determine if the proliferation of oral and intestinal pathogens could lead to the activation of JM


Lay Summary of Selected Cure JM Supported Research

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