Functional Restoration of Salivary Glands
Xerostomia is a frequent side effect of external beam radiation therapy (XRT) for head and neck cancer and is not amenable to palliative therapies. This medical and quality of life issue thus remains an unmet healthcare need for the increasing number of individuals who will receive XRT treatment for this disease of increasing incidence. A recent approach for this disorder is based upon gene therapy restoration of salivary gland function. In this strategy, a recombinant adenoviral vector (Ad) is employed to deliver the aquaporin gene to epithelial cells of the salivary glands via direct intra-ductal instillation. Preliminary phase I human clinical trials at the NIH/National Institute of Dental Research have clearly shown that this approach can restore salivary flow with an amelioration of xerostomia symptoms. Based on these promising findings, it is logical to hypothesize that vector design advancements to improve further aquaporin gene delivery could enhance functional restoration of the salivary gland. In addition, the achievement of long term expression of the aquaporin gene would extend the symptomatic benefits of this gene therapy approach for xerostomia. Herein we will seek to address these vector aspects of xerostomia gene therapy to enable its full patient benefit value to be realized as a translational therapeutic.