Gene Transfer Triggers Saliva Production
By Jody Dove
Using gene transfer technology in animals, scientists at the National Institute of Dental Research have tricked non-fluid-producing cells into making saliva. Their work could one day lead to a new treatment for the thousands of Americans whose salivary glands are damaged by radiation therapy for head and neck cancer.
While head and neck radiation therapy kills cancerous cells, it also often destroys the acinar (fluid-producing) cells of salivary glands that lie within the field of radiation. When this occurs, patients are unable to produce adequate saliva, and as a result suffer a host of long-term problems including xerostomia (dry mouth), inflammation of the mucous membranes lining the mouth, dental caries, frequent infections of the mouth and pharynx, and difficulty with swallowing, speech, and taste. Although clinicians and researchers have recognized these side effects for nearly a century, they have had little to offer patients in the way of treatment.
Now NIDR researchers may have found a way around the problem by coaxing cells into doing what doesn't come naturally. Unlike acinar cells, ductal cells in salivary glands frequently are not destroyed by irradiation. But ductal cells lack the ability to make or secrete saliva. The researchers sought to re-engineer ductal cells into fluid-producing cells by giving them the gene for an aquaporin protein. Aquaporins are a recently discovered family of proteins that form pores in cell membranes, through which fluid can pass.
The scientists inserted an aquaporin gene into an adenovirus -- similar to a cold virus -- that had been genetically altered so it could not reproduce. After irradiating the salivary glands of rats to significantly diminish saliva production -- mimicking what happens to head and neck cancer patients following radiation therapy -- the researchers infected the animals' salivary glands with the adenovirus carrying the aquaporin gene. Remarkably, the rats' salivary glands produced fluid. The researchers reported their results in the Apr. 1 issue of the Proceedings of the National Academy of Sciences.
Although the investigators caution that it may be several years before this technique can be tried in humans, they are optimistic about the potential use of the therapy for restoring salivary gland function. "It is an important first step to managing a condition for which no suitable and effective therapy is currently available," said Dr. Bruce Baum, chief of NIDR's Gene Therapy and Therapeutics Branch and principal investigator on the study.
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