Gene Therapy Studies in the Sinuses of CF Patients

John A. Wagner, M.D., Ph.D., Molecular Pharmacology Department Stanford University School of Medicine

Fall 1997

In the Phase I gene therapy trials, an adeno-associated virus vector, AAV-CFTR, was used to transfer CFTR cDNA into respiratory epithelial cells of the maxillary sinuses of ten CF patients. The maxillary sinuses are used (as opposed to the lungs where the life-threatening complications of CF occur) because their disease is similar to that occurring in the lungs. CF sinuses have similar physiology, including malfunctioning CFTR, similar infections, especially Pseudomonas aeruginosa, and similar disruptions in clearance of secretions. In addition, the sinuses are easier to access than the lungs, safer for the patients, and still allow researchers to evaluate how gene therapy affects the clinical course of CF. Another advantage is that the opposite, untreated sinus can be used as a control. If gene therapy proves effective in treating CF sinusitis, then it may also prove effective in treating CF lung disease. The Phase I portion of Dr. Wagner's study was to test the efficacy and safety of the vector (the means by which the gene therapy is delivered). Results were very encouraging.

Dr. Wagner received permission, and has lately begun his Phase II trials, a randomized, double-blind, placebo-controlled, within-subjects clinical study of the effects of AAV-CFTR on the clinical recurrence of sinusitis in CF patients. That is, he can now look beyond safety issues to issues of clinical efficacy. Results are not in, and neither doctors nor subjects know which sinus is being treated with the gene therapy, however Dr. Wagner did tell us that some cases of unilateral sinusitis had been reported. Dr. Wagner is looking for additional volunteers for the Phase II trials, so if you are interested and you have had the sinus surgery discussed in Dr. Victoria King's article, contact Dr. Wagner at (650) 723-9812.

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