Administrative Core: Abstract The Center for Gene Therapy at The Research Institute of Nationwide Children's Hospital (RINCH) has a dedicated translational program that targets the muscular dystrophies, with a particular longstanding interest in developing meaningful therapies for the most common forms, including Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Our Center's goals include unraveling disease pathogenesis and developing new treatment paradigms that can be translated from the bench to the bedside, and under this CORT proposal we seek to accelerate this translational process. Project 1 (PI, Paul Martin, PhD) seeks extend a therapy now entering trials in DMD to other forms of muscular dystrophy by applying the overexpression of Galgt2, an enzyme that alters skeletal muscle glycosylation, to boost the expression of proteins that ameliorate disease. Project 2 (PI, Scott Harper, PhD) explores novel approaches to modulating the expression of the DUX4 gene to treat the relatively common and debilitating FSHD. Project 3 (PI, Kevin Flanigan, MD) seeks to rapidly translate a newly discovered mechanism for dystrophin translational control into meaningful therapy for boys with DMD. The role of the Administrative Core will be to (1) facilitate scientific integration among these three projects; (2) oversee the budgetary and reporting aspects of the CORT; (3) develop and organize the Advisory Board's efforts; and (4) cultivate or identify pilot and feasibility projects for submission to the NIAMS for funding consideration. On a broader level, the Administrative Core will be responsible for maximizing the synergy between this CORT and other existing translational efforts at RINCH, and at the Ohio State University.
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| Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K et al. (2018) Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD. Mol Ther Methods Clin Dev 8:121-130 |
| Giesige, Carlee R; Wallace, Lindsay M; Heller, Kristin N et al. (2018) AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD. JCI Insight 3: |
| Zygmunt, Deborah A; Crowe, Kelly E; Flanigan, Kevin M et al. (2017) Comparison of Serum rAAV Serotype-Specific Antibodies in Patients with Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Inclusion Body Myositis, or GNE Myopathy. Hum Gene Ther 28:737-746 |
