Juvenile myositis (JM) is a rare, complex, multi-system condition in which inflammation of the muscles results in weakness as well as a characteristic skin rash in cases of juvenile dermatomyositis (JDM). The exact cause or pathogenesis of JM is not well understood but it is thought to result from a combination of multiple genetic and environmental risk factors. Treatment is generally empiric with prolonged and high-doses of immunosuppression medications including glucocorticoids, which carry significant adverse effects.  

Sixty to seventy percent of patients have a chronic disease course, and some are unable to achieve remission with currently available medications. In the long term, the disease often causes damage such as calcinosis and impaired function. Better markers to help monitor and predict the disease course and guide therapy are needed, as well as more targeted therapy options with better efficacy and fewer side effects.

Our group studies dysregulated gene and protein expression from patients with JM to better understand dysregulated biology and the pathogenesis of the disease. An interferon response signature has been demonstrated in peripheral blood, muscle, and skin in dermatomyositis. To better understand the role of interferon in JDM, we have compared the peripheral interferon signature, or score, in JDM to autoinflammatory Mendelian interferonopathies (PMID 32252809, PMID 29638206). Janus kinase (JAK) inhibitors can target this interferon signaling pathway. Given the interferon signature, which is well described in JDM, and previous use of JAK inhibitors in Mendelian interferonopathies, we studied the use of baricitinib (a JAK inhibitor) in refractory JDM, demonstrating proof of concept in pharmacodynamic studies as well as clinical efficacy (PMID 32843325).

These studies have highlighted how we have looked at particular pathways and utilized Mendelian disease to better understand pathogenesis and guide the selection of targeted therapy.

Research Focus

Our collaborative group studies are focused on better understanding the etiology and mechanisms of disease in juvenile myositis in order to optimize management and treatment. We are focused on:

• Elucidating the immunopathogenesis of the disease and potential predictors of treatment response by the discovery of novel biomarkers through transcriptomic, proteomic, and/or immunophenotyping analyses.
• Investigating novel treatments in small clinical trials to establish more targeted therapy with the goal of identifying safe treatments with greater efficacy and fewer side effects.