The human immune system presents a potentially serious barrier to treatment of Duchenne muscular dystrophy (DMD). Pre-existing T cell immunity to dystrophin has been observed in patients vi^ith DMD. Moreover, in subjects with large deletions in the dystrophin gene, sequences that are unique to a therapeutic dystrophin transgene can prime T cell immunity. Further complicating the picture are humoral and cellular immune responses to the AAV capsid that have the potential to interfere with vector-mediated transduction of muscle. This MD-CRC Center is structured to provide insight into cellular immune responses to dystrophin or AAV capsid proteins in DMD patients who are candidates for therapies that include gene replacement, exon skipping, and stop codon suppression. The Immunology Core has two objectives that support the proposed Center. The first is to provide access to well-established assays for standardized quantification of T cell responses to dystrophin and AAV capsid proteins in human subjects with DMD. The second objective is to adapt advanced technologies for monitoring immunity to the study of DMD. This includes methods for direct visualization of dystrophin-specific T cell responses in human subjects and to assess their function in target tissues like muscle.

Public Health Relevance

The Immunology Core is designed to provide standardized, reproducible analysis of cellular immune responses to dystrophin humans with Duchenne Muscular Dystrophy (DMD). Facilitating the analysis of immunity in Projects 1 and 2 has considerable relevance to treatment of progressive muscular disease associated caused by DMD.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD066409-05
Application #
8685780
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
City
Columbus
State
OH
Country
United States
Zip Code
43205
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