The human disease, in which nerves in the esophagus die, is similar to a disease that has been killing parrots, macaws, and other exotic birds in colonies worldwide. In the May 26, 2010, issue of Science Translational Medicine, Howard Hughes Medical Institute (HHMI) researchers propose that the bird disease is a model for understanding the origin of nerve damage in achalasia.
“It’s going to be a difficult search, and one that will require us to deploy very complex methodology. But the hunt is on.”
Joseph L. DeRisi
Normally when people eat or drink, wave-like contractions and relaxation of muscle in the esophagus move food or liquid toward the stomach. A muscular valve called the lower esophageal sphincter controls movement of food between the esophagus and the stomach. Achalasia causes nerves that relax the smooth muscles and sphincter to fail and ultimately die. As a result, passage of food and liquids becomes severely limited and uncomfortable. Surgery can treat the condition, but it usually recurs.
Domestic parrots, macaws, and related species of birds bred in colonies for sale are vulnerable to a disease with many of the same symptoms as achalasia. In birds, the condition is usually fatal. The disorder has been spreading among breeding colonies of 50 related species of birds on four continents and is considered the leading threat to the health of colonies worldwide.
The bird disease pops up in sporadic outbreaks, leading scientists to hypothesize some years ago that an infectious agent was the cause. In 2008, HHMI investigators Don Ganem and Joseph DeRisi and colleagues at the University of California, San Francisco searched for such a pathogen using the Virochip, a microarray tool that they developed that contains partial genome sequences of every known virus. If sequences of DNA or RNA in a snippet of diseased tissue match any of the microarray sequences, researchers can identify the responsible virus.
With the Virochip, the researchers discovered a previously unknown virus that they called avian bornavirus in birds that had the disease. Now the same team has catalogued a series of strong similarities between the bird infections and human achalasia.
“In human achalasia, we know that nerves regulating the motility of the esophagus are attacked by the body’s own lymphocytes,” said Ganem, who is the senior author on the paper. “The question has always been: What causes this attack? In the case of the affected parrots, the cause is clearly infection by this new virus. This raises the possibility that viral infection might be a trigger in the human disease as well.”
In the research article in Science Translational Medicine, Ganem, DeRisi, and postdoctoral fellow Amy Kistler document the similarities between human achalasia and the bird disorder, known as proventricular dilation disease, or PDD. The bird foregut is more complex than in humans, but as in humans, PDD involves disruption of peristalsis. Tissue known as the proventriculus, which is comparable to the human esophagus, becomes diseased and the immune system’s infection-fighting lymphocytes invade and destroy the nerve ganglia. Lymphocyte invasion of esophageal nerves is also a hallmark of the human disease.
In the birds, the virus causes the initial infection leading to nerve death. The team emphasizes that the bird virus is not the cause of human achalasia, and it has not yet identified a virus specifically linked to patients with achalasia. In their search for virus infection in the human disease, the team has employed both the Virochip and, more recently, high-throughput DNA sequencing.
“It’s going to be a difficult search, and one that will require us to deploy very complex methodology,” says DeRisi, “But the hunt is on.” He and his colleagues clearly relish the thrill of the chase.
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