Contact

➤ LOCATION

University of Washington
South Lake Union
850 Republican St, S241
Seattle, WA 98109-8055

☎ CONTACT

jsc5@uw.edu
(206) 616-6645

PROJECT 1
Translational and pre-clinical studies of muscular dystrophy gene therapy using AAV

Project 2
Facioscapulohumeral Dystrophy Clinical Trial Foundations

Principal Investigator: Jeffrey S. Chamberlain
Co Investigators: Joel R. Chamberlain, Stephen D. Hauschka, Fawn A. Leigh, David L. Mack, Guy L. Odom, and Michael Regnier

Principal Investigator: Stephen J. Tapscott
Co-Investigator: Seth D. Friedman, Peter L. Jones, Dennis W. Shaw, Jeffrey Statland, Rabi N. Tawil, and Leo H. Wang

The Seattle Wellstone research groups have made major contributions to adeno associated viral vector (AAV)-mediated gene delivery in murine and canine models of DMD. The success of these efforts has provided critical foundations for the ongoing clinical trials of AAV-delivered micro-dystrophin in boys with Duchenne muscular dystrophy. This project will continue to conduct translational and pre-clinical studies of muscular dystrophy gene therapy. Studies in this project will (a) improve the function of the micro-dystrophin gene, with a focus on cardiac muscle, and identify therapies that act to improve the functional benefit conferred by micro-dystrophin; (b) adapt these AAV-mediated delivery methods to achieve the suppression of human DUX4 in a preclinical mouse model of FSHD; and (c) establish a clinical trials readiness for participation in AAV-mediated therapeutic trials in DMD that will synergize with the infrastructure developed by our Wellstone MDSRC for FSHD trials. This will incorporate Seattle in future AAV-mediated DMD national trials and expand the scope of muscular dystrophy clinical trials and therapies available to the families of the Northwest.

The Seattle Wellstone research groups and their collaborating institutions have made major contributions to determining the pathophysiologic mechanisms of FSHD and to developing FSHD clinical trials infrastructure in Seattle. Previously, our Wellstone MDSRC established correlations between functional assessments, MRI characteristics, and molecular markers in FSHD. Studies in this project will (a) determine whether the correlation between candidate molecular biomarkers and MRI characteristics identified previously by our Wellstone MDSRC predict functional progression; (b) determine whether the correlation and predictive value of the candidate molecular biomarkers and MRI characteristics identified in the first cohort can be validated in an independent cohort; and (c) determine the molecular phenotype of the infiltrating mononuclear cells in areas of inflammation and whether this represents an oligoclonal T-cell response. Significantly, this study will identify and validate measurements that predict disease activity and progression in FSHD muscles that will inform rigorous trial design for future therapeutic trials.

• Promotes a Center environment through enhanced communication and collaboration of investigators within and outside the Center.

• Organizes the Center Advisory Committee made up of non-Center members.

• Organizes research meetings and seminars with internal and external speakers.

• Manages the Outreach program, which includes opportunities to visit the Center, meet investigators, provide speakers at events with patients and advocacy groups & present educational activities at local schools and science events.

• Provides consulting, reagents, and training related to adeno-associated (AAV) and lenti viral vector production.

• Provides high-quality, high-titer AAV and lentivirus vectors.

• Provides muscular dystrophy-related reagents (cell lines, cDNA, vector backbones, protocols, antibodies, etc).

• Provides services to members of this Center and outside laboratories (on a recharge basis) to support national efforts related to gene therapy for the muscular dystrophies.