Muscle targeted immunosuppression as an FSHD therapeutic

Budget

US$205,000
FSHD Canada Foundation Contribution: US$25,000 (Establishment Phase)

Lay Abstract

Investigator: Andreia Marcelino Nunes, PhD; University of Nevada, Reno School of Medicine

FSHD is caused by aberrant increased expression of the DUX4 gene in skeletal myocytes, which initiates a pathogenic cascade with detrimental effects on muscle function. The underlying pathogenic mechanisms are largely unknown; however, several studies support a major role for the immune response in FSHD pathology. We have found that a key component of the immune response is elevated in our FSHD-like mouse models and this result was independently confirmed in human FSHD patients by our collaborators. While this finding might provide a useful circulating biomarker for FSHD disease progression, it may also represent a potential therapeutic target. The efficacy of immunosuppression to control disease progression has been successfully implemented for other inflammatory disease conditions such as rheumatoid arthritis, anemia and most recently COVID-19. In this project, we will determine the efficacy of muscle targeted immunosuppression towards alleviating pathology in our DUX4-expressing FSHD-like mouse model. In aim 1, we will test the effect of immunosuppression to prevent muscle damage induced by acute DUX4 expression. In aim 2, we will evaluate the efficacy of immunosuppression to revert the muscle damage induced by exposure to long-term DUX4 expression. This project will provide a preclinical assessment of immunosuppression as a potential therapeutics for FSHD.