A small clinical study has demonstrated the safety and biologic efficacy of applying gene therapy to the human salivary gland in order to repair damage caused by radiation for head and neck cancer.

The phase 1 trial featured the gene aquaporin-1. This gene encodes a protein that forms water channels in cell membranes to help move fluid, as occurs when the cells of salivary glands secrete saliva into the mouth. No conventional therapy exists for salivary hypofunction in persons with head and neck cancer with late grade 2 to 3 toxicity as classified by Radiation Therapy Oncology Group scores, noted a team headed by Bruce J. Baum, DMD, PhD, (Proc Natl Acad Sci USA. 2012;109[47]:19403-19407).

A recently retired scientist with the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health, Baum explained in a statement issued by the NIDCR that in his work in the institute’s dry-mouth clinic he encountered numerous people who had undergone radiation therapy to shrink tumors in the head and neck. Although the treatment successfully fought the cancer, it left patients with damaged salivary glands that compromised their ability to secrete saliva.

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Over the years, Baum and his colleagues conducted animal studies showing that the transferred aquaphorin-1 gene could create new water channels in impermeable salivary gland cells. The first human patients underwent this treatment in 2008. The 11 study participants, all of whom were survivors of head and neck cancer, received a single dose of aquaphorin-1 packaged in a disabled adenovirus and injected directly into one of the two parotid salivary glands.

Within the study period of the first 42 days posttreatment, five patients experienced increased levels of saliva secretion and a renewed sense of moisture and lubrication in the mouth. Six patients did not benefit from gene therapy, but none of the participants suffered serious adverse events or dose-limiting toxicities. The few adverse events that occurred were all considered mild or moderate, the most common being a transient immune response against the disabled adenovirus.