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The use of gene-transfer technology to repair salivary-gland tissue, allowing a pathway for saliva to flow in patients undergoing radiation therapy for head and neck cancer is possible in principle, disclosed Bruce J. Baum, DMD, PhD.
Dr. Baum, who is chief of the Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md., spoke about the breakthrough study to attendees at the American Dental Association’s National Media Conference, held here today.
“We hypothesized that the major impediment to saliva flow from these irradiated, nonsecreting cells was the absence of a pathway for water in their membranes,” he explained. “Our strategy was to transfer a gene for a water channel protein into the radiation-surviving cells that would function as the pathway.”
Each year in the United States, the salivary glands of some 40,000 individuals are exposed to ionizing radiation (IR) during therapy for head and neck cancer. They experience irreversible salivary gland damage. In addition, patients with dry mouth or Sjogren’s syndrome (SS), (an autoimmune disorder characterized by progressive destruction of the lacrimal and salivary glands) also suffer the loss of salivary secretory tissue. Many patients receiving IR or those with SS experience complete gland destruction.
The primary function of salivary glands is to make saliva, the oral fluid that provides the major lubrication and protection for the mouth and upper gastrointestinal tract. In the absence of saliva, patients have difficulty swallowing food, develop mucosal infections like candidiasis, experience rampant dental decay, and suffer considerable pain and discomfort.
Salivary glands also may be useful target sites for gene-based protein replacement therapies (using transferred genes as drugs) with certain systemic deficiency disorders and for local oral diseases, Dr. Baum said.
“One obvious application for this concept is to augment saliva with gene products for upper-gastrointestinal (GI) tract disorders,” he explained. “Salivary secretions saturate the upper-GI tract lining continuously, and we envision both preventive and healing applications. An alternative strategy is to direct needed therapeutic proteins into the bloodstream for systemic use.”
Using rodent models in studies, we showed that salivary gland repairing and therapeutic applications are possible in principle, he said.
“In addition,” Dr. Baum said, “there is a realistic opportunity to develop a first-generation artificial salivary gland suitable for initial clinical testing relatively soon, within about 10 years.”
A pilot program to develop an artificial salivary gland for patients with little to no remaining secretory tissue was initiated several years ago.