Cystic Fibrosis Clinical Trial
Cystic Fibrosis
Cystic Fibrosis (CF) is an autosomal recessive disease associated with early death due to recurrent pulmonary infections and obstructive lung disease. The gene responsible for CF was identified in 1989: it expresses a protein involved in a regulation of salt and water in epithelial cells such as the conducting airway cells of the lung. Investigators at the IHGT were recently approved to begin a Phase I Clinical Trial of gene therapy for adults with CF.Extensive experiments in animals have indicated that a gene delivery vehicle based on a human adenovirus efficiently transfers the normal CF gene into the airway of epithelial cells of the lung. A recombinant form of this adenovirus has been created in which some of the disease-causing genes have been eliminated and the normal CF gene has been incorporated into the viral genome. The concept is to administer the virus directly into the airway of the patient thereby targeting the appropriate cells and correcting their genetic defect. The initial clinical trials of adenovirus for CF indicated that the first generation constructs were not completely disabled, causing some level of inflammation and premature ablation of the therapy. Investigators at the IHGT have created a third generation recombinant adenovirus that is more disabled and provides an improved safety profile. They are initiating a Phase I Clinical Trial for the use of this third generation vector in adults with CF. Eligible patients receive the virus into a segment of their lung by a bronchoscope. Follow-up includes two subsequent bronchoscopies to harvest cells to determine if gene transfer has been accomplished. This is a dose escalation study in which each patient receives a single dose of vector beginning with the lowest dose in the early cohort patients and advancing to the higher doses as safety data are accumulated. A total of 14 additional patients are needed to complete the study.
For more information, see:
Gene Therapy for Cystic Fibrosis (CF) Division of Pulmonary
and Critical Care, Department of Medicine