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Medical Network

Spring, 2021

Abstract of Comparison of Lesional Juvenile Myositis and Lupus Skin Reveals Overlapping Yet Unique Disease Pathophysiology

Jessica L. Turnier, Lauren M. Pachman, Lori Lowe, Lam C. Tsoi, Sultan Elhaj, Rajasree Menon, Maria C. Amoruso, Gabrielle A. Morgan, Johann E. Gudjonsson, Celine C. Berthier, and J. Michelle Kahlenberg.

Objective: Skin inflammation heralds systemic disease in juvenile myositis, yet we lack an understanding of pathogenic mechanisms driving skin inflammation in this disease. We undertook this study to define cutaneous gene expression signatures in juvenile myositis and identify key genes and pathways that differentiate skin disease in juvenile myositis from childhood-onset systemic lupus erythematosus (SLE).

Methods: We used formalin-fixed paraffin-embedded skin biopsy samples from 15 patients with juvenile myositis (9 lesional, 6 nonlesional), 5 patients with childhood-onset SLE, and 8 controls to perform transcriptomic analysis and identify significantly differentially expressed genes (DEGs; q ≤ 5%) between patient groups. We used Ingenuity Pathway Analysis (IPA) to highlight enriched biologic pathways and validated DEGs by immunohistochemistry and quantitative real-time polymerase chain reaction.

Results: Comparison of lesional juvenile myositis to control samples revealed 221 DEGs, with the majority of up-regulated genes representing interferon (IFN)-stimulated genes. CXCL10, CXCL9, and IFI44L represented the top 3 DEGs (fold change 23.2, 13.3, and 13.0, respectively; q < 0.0001). IPA revealed IFN signaling as the top canonical pathway. When compared to childhood-onset SLE, lesional juvenile myositis skin shared a similar gene expression pattern, with only 28 unique DEGs, including FBLN2, CHKA, and SLURP1. Notably, patients with juvenile myositis who were positive for nuclear matrix protein 2 (NXP-2) autoantibodies exhibited the strongest IFN signature and also demonstrated the most extensive Mx-1 immunostaining, both in keratinocytes and perivascular regions.

Conclusion: Lesional juvenile myositis skin demonstrates a striking IFN signature similar to that previously reported in juvenile myositis muscle and peripheral blood. Further investigation into the association of a higher IFN score with NXP-2 autoantibodies may provide insight into disease endotypes and pathogenesis.

Full article here. Please note, this paper is currently not open access.

Vamorolone Update

Eric Hoffman, Ph.D., President, CEO, and Vice President of Research at ReveraGen, offers an update on the development of the drug vamorolone.

The drug is a potentially significant replacement for the standard of care steroids used to treat juvenile dermatomyositis (JDM).

In this video, Dr. Hoffman details that standard of care steroids have two mechanisms of action: transactivation and transrepression. The former leads to an array of unwanted side effects and the latter to the efficacy of steroids. Vamorolone has been demonstrated to have significantly less transactivation while retaining similar levels of transrepression, which is ideal for a steroid replacement. Vamorolone is currently in a licensure trial for Duchenne's Muscular Dystrophy and the submission of the new drug application is expected in early 2022, with expected approval 6-9 months later.

You can read the recently released topline results of the study of the efficacy and safety of vamorolone compared to placebo and prednisone in the treatment of Duchenne's Muscular Dystrophy, here.

The ReveraGen, Duke University, and Cure JM team are looking at how to start a clinical trial of this exciting drug in a JDM cohort of patients.


The Importance of Exercise in Juvenile Myositis

This Town Hall explored the importance of different types of exercise in the management of JM and was presented by Sue Maillard, a specialist physiotherapist at Great Ormond Street Hospital, London.

Biggest takeaways included:

  • Exercise is safe, at all stages of disease activity
  • Exercise is vital to maximize independence, strength and mobility
  • Exercise may slow the disease progress and reduce inflammation
  • Exercise is vital for any degree of recovery and repair

Maillard completed research in the safety of exercise in JDM and leads a physiotherapy team to provide an inpatient rehabilitation program for children, as well as reviewing and managing home treatment programs.

Cure JM’s Partnership with NIH, FDA and Our Centers of Excellence

Cure JM’s Executive Director presented a Proclamation of Thanks to NIH’s Chris Austin, MD during our observance of Rare Disease Month. Dr. Austin is the Director of the National Center for Advancing Translational Sciences (NCATS) at NIH, where Cure JM has been funding an important drug discovery program over the past several years. You can watch the presentation of the Proclamation of Thanks here.

The Proclamation recognizes three important NIH divisions that have demonstrated a commitment to juvenile myositis research and clinical care—NCATS, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Institute of Environmental Health Sciences (NIEHS). The leadership and researchers within these three institutes are hard at work to discover new drugs to better treat JM, and to run the human clinical trials to prove that these drugs are safe and effective in JM.

Because human clinical trials for JM must be approved by the FDA, Cure JM is working to ensure that the challenges JM patients and families face each and every day and the need for better therapies are well understood by the FDA regulators.

Five Cure JM families recently appeared before the FDA to raise JM's profile and testify for the critical need for better drugs. Many thanks to Nikki and Addie Hahn, Kendall and Vickie Tiffany, Sasha and Zamaya Sumling, Shari Hume, and Kristine and Katherine Alderfer for bravely sharing their stories and making sure that the FDA knows about juvenile myositis and understands the urgent need for better treatments to treat JM.

The Cure JM Board of Directors has approved increases in grants to three Cure JM Centers of Excellence at Duke University and Children's Hospital, George Washington University Hospital, and Seattle Children's Hospital/University of Washington.

Duke University is taking the lead in advancing a clinical trial for vamorolone. Vamorolone is a newer steroid that does not have most of the side effects of other steroids, such as prednisone. Vamorolone is not yet approved for use in any disease, but a clinical trial for another pediatric autoimmune disease is nearing completion, and the drug's eventual approval by the FDA could revolutionize JM treatments. When approved, Cure JM's goal is for the FDA to next approve a JM trial that, if successful, will lead to vamorolone’s use in JM children.

Similarly, the Cure JM Center of Excellence at George Washington University has enrolled the final patient in a clinical trial for a drug known as abatacept, also known under its trade name, Orencia. The hope is that the results of this trial, to be completed this year, will provide safety and efficacy information that will lead to increased use and availability to use the drug in JM. It is certainly possible that Orencia’s manufacturer, Bristol-Meyers Squibb, will petition the FDA for approval in JM. Orencia is already approved for use in another pediatric autoimmune inflammatory disease—a form of juvenile arthritis.

This issue is brought to you with the support of:

Bristol Myers Squibb logo
CSI Pharmacy Clinical Specialty Infusions, LLC
Pharmaceutical Companies of Johnson & Johnson

Cure JM welcomes your input, questions and experiences. Please email to share your input.