1. Gene Therapy for Arthritis, Musculoskeletal, and Skin Diseases Group leaders and participants -Dr. Glen Nuckolls -Dr. Paul Robbins Program Director Professor, Microbiology and Molecular Genetics, Division of Musculoskeletal Diseases, NIAMS and Biochemistry University of Pittsburgh -Dr. Carl C. Baker Program Director Division of Skin and Rheumatic Diseases, NIAMS -Dr. Dennis Roop Charles C. Gates Chair of Regenerative Medicine and Stem Cell Biology -Ms. Shahnaz Khan University of Colorado Denver Clinical Coordinator Division of Extramural Research Activities, NIAMS -Ms. Anna Nicholson Clinical Coordinator Division of Extramural Research Activities, NIAMS -Dr. Louise Rosenbaum Science Policy Analyst Office of Science Policy and Planning, NIAMS Overarching question -What high priority, basic research questions should be addressed to advance the field of gene therapy? 2008 NIAMS Scientific Retreat

2. Uses of Gene Therapy Advantages of gene therapy (GT) -Potential replacement or correction of single gene defects -Up- or down-regulation of pathways involved in pathology or natural repair mechanisms -Synthesis, processing, and delivery of GT products at the disease site Application of GT to Arthritis, Musculoskeletal, and Skin Diseases -Wound-healing: delivery of platelet-derived growth factor b gene to lesions -Rheumatoid arthritis: injection of ex vivo-manipulated synovial cells into joints -Osteoarthritis: targeting interleukin 1 receptor antagonist gene to affected knee joints -Limb-girdle muscular dystrophy: intramuscular delivery of alpha-sarcoglycan gene 2008 NIAMS Scientific Retreat

3. Points of consideration Vector optimization, selection, and delivery -In vivo delivery, ex vivo manipulation options -Stem cells: only curative approach Immune response -Primary obstacle for successful GT -Approaches: transient immune suppression, long-term tolerance strategies Infrastructure and resource needs -Central services for pre-clinical testing and vector production -Activities (meetings, funding opportunities) to facilitate formation of multidisciplinary collaborations Regulatory and review issues -Increased federal requirements -Importance of multidisciplinary peer review for GT grant applications 2008 NIAMS Scientific Retreat