03 Dec The Chris Carrino Foundation Board Approves Continued Funding for UMass FSHD Research Project

The Board of Directors of the Chris Carrino Foundation for FSHD has proudly approved the funding of $107,777 to Peter Jones, PhD and Takako Jones, PhD at the University of Massachusetts for their mouse model research project. It is an expansion of research funded by our foundation last year, which was a tremendous success.

Below is a summary of the project and a statement from the researchers:

Project: An FSHD model for therapeutic development

PIs: Peter Jones, PhD and Takako Jones, PhD

University of Massachusetts Medical School, Worcester, MA USA

FSHD is caused by the aberrant toxic expression of the DUX4 gene in particular skeletal muscles, leading to the gradual deterioration of the muscle and clinical weakness. Thus, the DUX4 gene is widely considered to be the best target for designing therapeutic interventions. Recently, the FSHD research field has developed several promising strategies for targeting the expression of the DUX4 gene and the function of the DUX4 protein. While these advances are encouraging, due to the lack of an FSHD-like mouse model there is still no evidence that any of these approaches will be therapeutically beneficial. The goal of this project is to fill this void in the therapeutic development pipeline by genetically engineering mice that express DUX4 and exhibit FSHD-like progressive muscle weakness. In the first year of funding from the Chris Carrino Foundation we successfully generated mice harboring the human FSHD-associated DUX4 gene. Importantly, this gene is not expressed until we provide a signal that induces DUX4 expression. Thus, we are able to control the timing, level, and tissue distribution of DUX4 gene expression. This is significant because FSHD is generally a late onset muscle disease and we are interested in reversing the pathology in those already affected as well as preventing the onset or progression of FSHD in those susceptible to the disease. In this second year of funding we will manipulate our engineered DUX4 mouse model to determined the best conditions in which to turn on the DUX4 gene to generate reproducible FSHD-like pathology that is amenable to therapeutic screening. Once these conditions are determined, we will use these mice to test our own classes of anti-DUX4 molecules for the prevention, inhibition, and reversal of muscle weakness. We will also distribute the model so that other FSHD labs and interested pharmaceutical companies can test their candidate therapeutic molecules in these mice. Showing clear therapeutic benefit in an FSHD-like mouse model is an indispensable step in the path to clinical trials for FSHD. We thank the Chris Carrino Foundation for FSHD for providing the funding to make this project possible.