Injecting an adenoviral (Ad5) vector encoding human aquaporin-1 (hAQP1) into the parotid glands of head and neck cancer survivors improves their symptoms of dry mouth induced by radiation therapy, show study results.
Furthermore, no deaths, dose-limiting toxicities, or serious adverse events occurred as a result of the treatment, remark the researchers.
The findings represent a "unique direct gene-therapy clinical trial in the oral cavity for a nonmalignant condition and one of the few times that gene transfer has been used to treat a quality of life disorder," say Bruce Baum (National Institutes of Health, Bethesda, Maryland, USA) and colleagues in Proceedings of the National Academy of Sciences United States of America.
The team conducted their phase I study on 11 individuals who had been successfully treated for a squamous cell carcinoma (of the tonsil, base of tongue, or hypopharynx) with radiation therapy at least 5 years previously, but who had considerable oral morbidity.
Participants received the Ad5 vector containing hAQP1 (AdhAQP1) and were followed up for 42 days during which time more than three-quarters of the adverse events that occurred were unlikely to be related to the treatment, and the majority (90.8%) were mild (Grade 1).
One participant met criteria for a US Food and Drug Administration 3-month stopping rule, showing saliva (but not serum) that was positive for both replication competent adenovirus and AdhAQP1 on day 7 of the study. This adverse event was judged to be mild, was without clinical consequence, and resulted from activation of a latent Ad5 infection in the target gland, explain the researchers.
The team reports significant improvements in both the absolute volume of parotid gland salivary flow rates, from a median 0.115 mL/min at baseline to 0.153 mL/min at 42 days post-treatment, and the proportional change in flow, at a median 164.5% in six patients during days 7-42 of the study (responders).
Importantly, contend Baum et al, at the time of peak increase in flow rate, five of these individuals showed improvement in subjective perception of oral dryness and saliva presence, as measured on a visual analog scale.
"It is time to evaluate a different vector to deliver the Aquaporin-1 gene, one that will cause only a minimal immune response," said Baum in a press statement. "But these data will serve as stepping stones for other scientists to improve on this first attempt in the years ahead. The future for applications of gene therapy in the salivary gland is bright," he concluded.
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