Funding outcome

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy. It causes progressive weakness in the face, shoulders, arms and legs. It affects men and women equally. Most people with FSHD begin to show symptoms as teenagers. Once started, FSHD slowly robs people's ability to walk, talk, smile, or eat properly. The Infantile form of FSHD is even more severe; muscle weakness appears before the age of 5 and is associated with a high risk of major hearing and vision complications. Currently, there is no cure or treatment for FSHD. FSHD is caused by abnormal production of a toxic protein called DUX4 in muscle cells. DUX4 causes the cells to die, but it is not produced in a healthy state. My research aims to knock down DUX4 production so that the muscle cells can survive. I plan on using synthetic DNA-like molecules called gapmers to knock down DUX4 production. I will develop gapmers that are able to locate and destroy the gene products that make DUX4 precisely. To enhance the effectiveness and safety, I will chemically modify the gapmers. I will use a shuttle system made of nanosized grease balls called lipid nanoparticles to efficiently deliver the gapmers to muscle cells. This will also contribute to the effectiveness and safety of the treatment. I will test the gapmer in patient-derived muscle cells and in a mouse model for efficacy and safety studies. This study will facilitate efforts to treat FSHD so the patients, particularly children, find an opportunity to live without the restrictions of lifelong disability