Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

First Gene Therapy Study in Human Salivary Gland Shows Promise

Published: Tuesday, November 06, 2012
Last Updated: Tuesday, November 06, 2012
Bookmark and Share
Treatment proves safe and effective, helps cancer survivors with chronic dry mouth.

Gene therapy can be performed safely in the human salivary gland, according to scientists at the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health.

This finding comes from the first-ever safety, or Phase I, clinical study of gene therapy in a human salivary gland. Its results, published this week in the Proceedings of the National Academy of Sciences, also show that the transferred gene, Aquaporin-1, has great potential to help head and neck cancer survivors who battle with chronic dry mouth. Aquaporin-1 encodes a protein that naturally forms pore-like water channels in the membranes of cells to help move fluid, such as occurs when salivary gland cells secrete saliva into the mouth.

These initial results clear the way for additional gene therapy studies in the salivary glands. Although sometimes overlooked, salivary glands present an ideal target for gene therapy. They are easily accessible and, once a gene is introduced, it has no obvious escape route into the bloodstream, where it can have unintended consequences.

“You cannot imagine how fulfilling it is to jot down an idea on a napkin in 1991 and then see it enter a clinical trial and help people.,” said Bruce Baum, D.M.D., Ph.D., lead author on the study and recently retired NIDCR scientist who spent the last 21 years moving gene therapy in the salivary glands from the research bench to the clinic. “Can a scientist ask for anything better?”

Baum's interest in helping head and neck cancer survivors dates to the early 1980s. While attending to patients in the NIDCR's Dry Mouth Clinic, Baum encountered numerous people with head and neck cancer who had received radiation therapy to shrink their tumors. The radiation, while effective in treating cancer, had inadvertently damaged nearby salivary glands, compromising their ability to secrete saliva into the mouth.

Baum said he was thoroughly frustrated at the time because he had no effective moisture-restoring treatments to offer most patients. They had beaten cancer, but the radiation had left them with a permanent parched sensation in their mouths that diminished their quality of life and often led to chronic oral problems, such as difficulty swallowing, inflammation, infection, bad breath, and pain.

In the early 1990s, as the first gene-therapy studies entered research clinics, Baum saw an opportunity to make a difference. An initial napkin sketch of the procedure and 15 years of research later, Baum and his colleagues had assembled a compelling scientific case in animal studies that the transferred Aquaporin-1 gene, once expressed, will create new water channels in the impermeable salivary gland cells and allow water to flow through them. After rigorous reviews by NIH and the U. S. Food and Drug Administration, the Phase I protocol was launched and the first patients treated in 2008.

The scientists gave 11 head and neck cancer survivors a single-dose injection of the Aquaporin-1 gene directly into one of their two parotid salivary glands, the largest of the major salivary glands. The gene was packaged in a disabled, non-replicating adenovirus, the cause of the common cold when intact but incapable of causing a cold in this case. As is standard in gene therapy studies, the virus served as the vector, or Trojan horse, to deliver the gene into the cells lining the salivary gland.

The scientists found that five participants had increased levels of saliva secretion, as well as a renewed sense of moisture and lubrication in their mouths, within the study's first 42 days, the period covered in this report. Of the six who didn't benefit from gene therapy, none had serious side effects. The most common side effect was a transient and relatively minor immune response against the disabled adenovirus.

“It is time to evaluate a different vector to deliver the Aquaporin-1 gene, one that will cause only a minimal immune response,” said Baum. “But these data will serve as stepping stones for other scientists to improve on this first attempt in the years ahead. The future for applications of gene therapy in the salivary gland is bright.”

The National Institute of Dental and Craniofacial Research is the Nation's leading funder of research on oral, dental, and craniofacial health. For more information about NIDCR and its programs, visit http://www.nidcr.nih.gov/.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 4,000+ scientific posters on ePosters
  • More than 5,300+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Exploring the Genome of the River Blindness Parasite
Researchers have decoded the genome of the parasite that causes the skin and eye infection known as river blindness.
Wednesday, December 07, 2016
Gene-Editing Improves Vision in Blind Rats
Scientists developed a targeted gene-replacement technique that can modify genes in both dividing and non-dividing cells in living animals.
Wednesday, December 07, 2016
Protein-Folding Gene Helps Heal Wounds
Researchers identified a protein that dramatically accelerates wound healing in animal models.
Wednesday, November 23, 2016
NIH Researchers Unveil New Wound-Healing Role for Protein-Folding Gene in Mice
The study found that topical treatment of an Hsp60-containing gel dramatically accelerates wound closure in a diabetic mouse model.
Friday, October 28, 2016
Gene Editing Corrects Sickle Cell Mutation
Researchers demonstrate a potential pathway to developing gene-editing treatments for sickle cell disease.
Wednesday, October 26, 2016
NIH Scientists Uncover Genetic Explanation for Frustrating Syndrome
Researchers at NIH have suggested that the multiple alpha tryptase gene copies might underlie health issues that affect a substantial number of people.
Tuesday, October 18, 2016
NIH Commits $6.7 M to Advance DNA, RNA Sequencing Technology
"Can you believe they make DNA sequencers the size of staplers?" asked Meni Wanunu, Ph.D. "Ideas that were crazy twenty years ago are now happening!"
Friday, October 07, 2016
“Sixth Sense” More Than a Feeling
NIH study of rare genetic disorder reveals importance of touch and body awareness.
Monday, September 26, 2016
The Genetics of Blood Pressure
Researchers have identifed areas of the genome associated with blood-pressure including 17 previously unknown loci.
Wednesday, September 21, 2016
Catalogue of Human Genetic Diversity Expands
The largest data set of human exomes to date has been assembled to better study seqence variants and their consequences.
Wednesday, September 07, 2016
$12.4M Awarded to Neural Regeneration Projects
The National Institutes of Health will fund six projects to identify biological factors that influence neural regeneration.
Friday, September 02, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
Public Support for National Study
Survey shows the majority of respondents support or show willingness for national precision medicine study.
Thursday, August 18, 2016
Schizophrenia, Autism Share Genetic Causes
Monkey brain developmental atlas pinpoints when, where genes activate.
Tuesday, August 16, 2016
How Breast Cancers Resist Chemotherapy
Researchers discovered an unexpected way that breast cancers cells with mutant BRCA1 or BRCA2 genes acquire drug resistance and evade chemotherapies.
Wednesday, August 10, 2016
Scientific News
Big Genetics in BC: The American Society for Human Genetics 2016 Meeting
Themes at this year's meeting ranged from the verification, validation, and sharing of data, to the translation of laboratory findings into actionable clinical results.
Personality Traits, Psychiatric Disorders Linked to Specific Genomic Locations
Researchers have unearthed genetic correlations between personality traits and psychiatric disorders.
Genetics Control Regenerative Properties Of Stem Cells
Researchers define how genetic factors control regenerative properties of blood-forming stem cells.
Diabetes Missing Link Discovered
Researchers from the University of Auckland have shown that beta catenin plays a vital role in the control of insulin release from the pancreas.
Study Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity
Hippo pathway signaling regulates organ size by moderating cell growth, apoptosis and stem cell renewal, but dysregulation contributes to cancer development.
Gene-Editing Improves Vision in Blind Rats
Scientists developed a targeted gene-replacement technique that can modify genes in both dividing and non-dividing cells in living animals.
Gene Editing Yields Tomatoes That Ripen Weeks Earlier
Research team develop method to make tomato plants flower and ripen fruit two weeks faster than current growth rates.
Exploring the Genome of the River Blindness Parasite
Researchers have decoded the genome of the parasite that causes the skin and eye infection known as river blindness.
Gene Therapy Maintains Clotting Factor for Hemophilia Patients
Following a single gene therapy dose, the highest levels of an essential blood clotting factor IX were observed in hemophilia B patients.
Unexpected Role for Epigenetic Enzymes in Cancer
Researchers use epigenetics to identify the role of an enzyme family as regulators of genetic message interpretation in yeast.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
4,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!