Further Preclinical Progress In Salivary Gland Gene Transfer

This article tells of the progress in salivary gland gene transfer in patients undergoing therapy for head and neck cancer. There are more than 35,000 Americans receive radiation therapy to treat head and neck cancer every year. However, even if the radiation is helpful in getting rid of the tumor, it can also cause damage to the patient’s salivary glands. Radiation therapy causes a marked reduction in the patient’s salivary flow as an undesirable result. Specifically, the scientists explain that while head and neck therapy kills cancerous cells by radiation, it also often destroys the acinar cells of salivary glands. These cells are fluid producing, and they lie within the field of radiation. When this happens, the patients are unable to produce adequate saliva. As a result, most of them suffer long term problems including xerostomia or dry mouth, inflammation of the mucous membranes lining the mouth caused by poor lubrication, dental caries, frequent infections of the mouth and pharynx, and difficulty with swallowing, speech, and taste.

For several years, a group of NIDCR scientists has been developing a strategy to efficiently transfer a gene into irradiated salivary glands with the aid of teaching-microscope. They attempt such strategy in order to supplement or fully restore the patients undergoing the therapies salivary production. Using gene transfer technology in animals, the scientists have figured a way for the non-fluid producing cells into producing saliva. The scientists have found a way around the problem by coaxing cells. The researchers sought to reengineer ductal cells into fluid producing cells by giving them the gene for an aquaporin protein that can be seen under the teaching-microscope. Aquaporins are a family of proteins that form pores in cell membranes, through which fluid can pass.

In the scientists initial animal studies, they transferred genetic material encoding the well characterized water channel protein, human aquaporin 1, into the salivary glands of rats that had been exposed to radiation four months earlier and restored near normal salivary flow. In the experiment, scientists inserted the aquaporin gene into an adenovirus that had been genetically altered so it could not reproduce. After the scientists have irradiated the salivary glands of rats to significantly diminish saliva production, the researchers infected the animal’s salivary glands with the adenovirus carrying the aquaporin gene. They have found in their results that the rat’s salivary glands produced fluid that can be seen under the teaching-microscope.

However, the researchers follow up studies in rhesus monkeys led to equivocal results. This raised concerns about the clinical potential of aquaporin 1 gene transfer in people. The article explains that recently, the NIDCR scientists and their colleagues in China evaluated the human aquaporin 1 gene transfer strategy in another large, well-characterized animal model. They have been studying the effect of such therapy in miniature pigs. The scientist claimed that they have found that the gene transfer significantly increased salivary secretion without causing significant side effects. Although the investigators caution that it may be several years before this technique can be tried in human beings, they are optimistic about the potential use of the therapy especially for head and neck cancer patients undergoing radiation therapy for restoring salivary gland function. Read more