NEW YORK, Jun 16 (Reuters Health) - Gene transfer may be used to repair
salivary glands damaged by radiation therapy in patients receiving treatment for
head and neck cancer, or in patients with an autoimmune condition known as
Sjogren's syndrome, US researchers report.
Forty-thousand new patients are diagnosed with head and neck cancer in the
US each year, and another one million have Sjogren's syndrome.
Moreover, the salivary gland may one day be used as a gene delivery site for
a number of therapeutic proteins for delivery into not only the mouth, but into
the bloodstream.
There is no therapy currently available to restore salivary gland activity,
according to Dr. Bruce Baum, chief of the gene therapy and therapeutics branch
at the National Institute of Dental and Craniofacial Research at the National
Institutes of Health.
The salivary glands produce saliva, which bathes the mouth, enables
individuals to swallow food and is important for digestion, and protects the
mouth against mucosal infections and dental decay.
Speaking at an American Dental Association media briefing in New York on
Thursday, Baum said that his lab studied rodents to see if gene therapy could
restore salivary channels to the mouth. They were able to restore salivary gland
function in mice by transferring a gene using an adenovirus as a delivery
vehicle.
"These results provide considerable encouragement towards the possible
utility of such an approach to treat patients with radiation-induced salivary
malfunction," Baum said. He is currently investigating other vectors for use in
humans that would express for longer periods of time and not produce an immune
reaction, known to occur with adenoviral vectors.
Baum's group is also investigating the possibility of using functional
salivary glands as drug delivery devices, in combination with gene transfer,
whereby a gene for a particular protein, such as growth hormone or alpha
1-antitrypsin would be delivered to the gland. Therapeutic proteins would be
secreted by the salivary glands into the mouth as well as into the bloodstream,
which could make this approach useful for gastrointestinal problems as well as a
range of other applications.
"Salivary secretions saturate the upper gastrointestinal tract's lining
continuously, and we envision using that in both preventive and healing
applications," Baum explained. "Some scientists have found that the salivary
glands can secrete proteins directly into the bloodstream as well as into the
mouth. If this is true, it would offer many significant therapeutic
opportunities using gene transfer," he added.
"In addition, there is a pilot program in which we are developing a
first-generation artificial salivary gland for patients with little or no
remaining secretory tissue," Baum said. He and colleagues are experimentally
growing human submandibular gland cells on scaffolding to create an artificial
gland from the ground up. Such a gland could reach the clinic for human testing
within the decade, he noted.
