The primary aim of the Human Applications Core is to ensure that human trials involving patients with Cystic Fibrosis (CF) and other genetic disorders conducted within the Core Center for Gene Therapy are properly designed and implemented to maximize safety, validity and efficiency of these gene therapy trials. The objectives of the Core are to 1) collaborate with investigators within the Core Center in the design and implementation of preclinical studies to assure that necessary safety and efficacy data have been collected prior to initiation of human trials, 2) provide consultation for design and development of human trials, 3) provide personnel for patient enrollment, study implementation, data collection and statistical analyses of gene therapy trials, 4) provide regulatory consultation, 5) ensure safety of all research participants enrolled in gene therapy trials conducted through this P-30 program, 6) provide education and consultation to new investigators regarding conduct of clinical trials involving human gene therapy. In the previous grant cycle (1999-2003), the Human Applications Core (HAC) assisted in the design, conduct and completion of three human trials, two involving aerosol delivery of adeno-associated viruses (AAV) to the lower airway of patients with Cystic Fibrosis and one involving ex vivo transduction of retroviral mediated human CD18 cDNA to peripheral blood repopulating cells of patients with Leukocyte Adherence Deficiency (LAD). In the first year of the renewal period, the HAC will assist in development of five proposed human trials: 1. AAV mediated delivery of a marker gene, human placental alkaline phosphatase, to respiratory epithelium of patients with Cystic Fibrosis (Dusty Miller, PI) 2. Aerosolized tgAAVCF delivery to lower airway of patients with Cystic Fibrosis (collaboration with Targeted Genetics Corporation). 3. Preclinical study to assess the feasibility of gene replacement therapy in individuals with the primary immunodeficiency, Wiskott-Aldrich Syndrome (WAS) utilizing either a retroviral or lentiviral mediated vector system (David Rawlings, PI). 4. Preclinical study to assess the feasibility and optimal patient population to evaluate the safety of utilizing AAV vectors containing truncated yet functional mini dystrophin genes for in vivo transduction of myocytes from patients with muscular dystrophy. 5. A Phase 1 study of the safety of long-term delivery of glucose-regulated insulin to individuals with Type 1 Diabetes Mellitus (IDDM) by retroviral transduced autologous or allogeneic vascular smooth cells housed in subcutaneous bioisolator devices (Theracyte(R)). The benefits of the Core are to consolidate resources and ensure that human trials are designed and conducted to answer proper scientific questions in the field of gene therapy.
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