Report: Molecular Markers of FSHD

Report by Dr. Tapscott
See also Molecular Markers of FSHD

Several studies have defined the functional, MRI, and molecular measurements of disease progression in FSHD. This proposal seeks to address two important barriers to using this knowledge to rapidly advance therapeutic development. First, the development of an animal model that recapitulates the progression of FSHD in humans would greatly speed preclinical testing of therapeutic interventions. Mice have some utility as preclinical models, but evolutionary differences in DUX4 and the comparable mouse Dux limit the use of mice for studies of disease progression. In contrast to mice, human DUX4 and the comparable pig DUXC appear to have maintained similarity and the expression of human DUX4 in pigs cells has consequences very similar to expression in human cells. This proposal seeks to determine whether pigs will be a better model and will analyze gene expression and histology in two different models of FSHD based on the expression of DUX4 in pig muscle cells. During the first year of funding, RNA was analyzed from different pig muscles to determine the similarity of the pig model to human FSHD. The second goal of this proposal is to test whether cells of the immune system, T cells and B cells, are responding to FSHD muscle and circulating in the blood to other muscles of the body and possibly cause inflammation. During the first year of this award, conditions for isolating T and B cells were explored to develop the methodological approach to determine their identity and receptor sequences.