Impacts of corticosteroids treatment on skeletal muscles of bmx, a novel BMD mouse model.


Pre-Clinical Research

Poster Number: 224


Trinitee Oliver, Children's National Medical Center, Nikki McCormack, PhD, Children's National Research Institute, Nhu Nguyen, PhD, Children's National Medical Center, Christopher Tully, MS, Children's National Medical Center, Alyson Fiorillo, PhD, Children's National Medical Center (Washington, DC), Chris Heier, PhD, Children's National Medical Center

Corticosteroids are drugs used to treat inflammation in a wide range of diseases, including muscular dystrophy; however, their side effects (such as stunted growth, diabetes, weight gain, and brittle bones) negatively impact patient quality of life and lead to medical professionals not prescribing them for some indications. One disease that has not adopted widespread corticosteroid use is Becker Muscular Dystrophy (BMD), an X-linked genetic disease in which offspring have an in-frame mutation in the dystrophin protein. This protein helps to protect muscle fibers from injury. This project is part of the first preclinical bmx mouse study for Becker and tests if a novel dissociative corticosteroid, vamorolone, could treat inflammation and fibrosis in BMD while comparing it to a traditional corticosteroid, prednisone. The bmx mouse model deletes dystrophin exons 45-47 to mimic the most common mutations in BMD patients. We hypothesized that vamorolone will improve skeletal muscle pathology in bmx mice. Muscle function phenotyping showed improvements of bmx mouse strength in response to treatment. Here, histopathology of H&E and Laminin-DAPI immunofluorescence staining reveals that bmx skeletal muscle improves fiber size and centrally nucleated fibers upon treatment. Molecular analyses of inflammatory, dystrophic, and fibrotic gene targets prove vamorolone to be just as effective as prednisolone at treating inflammation and fibrosis in bmx mice. Together, our studies establish vamorolone as a therapeutic candidate for treating BMD patients.