October 15, 2003.
By Amanda Onion,
Lancelot, a 2-year-old briard, was blind before he became a patient of gene therapy. Now he has vision through his right eye. (Foundation Fighting Blindness) Canine Cures
Long before Shadow the poodle attained fame for becoming the first dog to be genetically mapped, a shaggy briard named Lancelot had already been shaking paws with lawmakers in Washington.
Since 2001, Lancelot has been a living model of how vision can be restored to the blind, and the gene therapy treatment that gave the briard sight is currently being vetted for human trials. But now that scientists have Shadow's mapped genome as a tool for finding new genes, there may be more medical miracles like Lancelot to come.
"Many genetic diseases in dogs resemble human diseases and probably share the same genes," said Ewen Kirkness, the leader of the team at the Center for Advancement of Genomics in Rockville, Md., that decoded Shadow's genes. "This will make the hunt for those genes easier."
Blind Dogs See
Kirkness' work showed that dogs share about 18,000 of some 24,000 clearly identified human genes and they host about 360 of the same genetic disorders that are known in humans. He explains that researchers can use the rough draft of Shadow's genes to zero in on regions where problematic genes are located.
Tracing genes in dogs is made even easier by the fact that dog breeders have kept decades worth of genetic histories for many breeds.
Kirkness says all these factors will help accelerate research. In fact, they already have.
Case in point: Lancelot. The briard and his two siblings were born in 2000 with a hereditary blindness condition known as Leber's disease. The puppies constantly smacked into furniture and huddled in corners.
By studying the dogs' genes, researchers were able to pinpoint the genetic source of their blindness. To treat Lancelot and his brother and sister, researchers injected a virus containing corrected copies of the gene into the dogs' retinas.
Within 90 days, Lancelot and his siblings showed signs of sight. Researchers chose Lancelot as the "public face" of the experiment since his sister reportedly has a testy temperament and the third pup in the group was reportedly euthanized to obtain more data.
"Lancelot's not bumping into tables, he's not cowering in the corner, he's a nice, happy mutt," said Gerald Chader, chief scientific officer at the Foundation Fighting Blindness in Owings Mills, Md. Chader has introduced the dog to Sen. Tom Harkin, D-Iowa, and Health and Human Services Secretary Tommy Thompson, among other political figures.
Since blindness is a common affliction in many inbred dogs, including Irish setters, poodles, mastiffs and corgis, Chader believes these animals may hold promise for the estimated 100,000 people who experience similar, if not identical, retinal problems. The treatment that gave Lancelot sight is now undergoing safety standards testing and may be available to people within three years.
Better Hips, Brains
Dogs and humans share many more afflictions besides blindness.
Linda Cork at Stanford University has traced genetic causes of motor neuron disease, cerebellar degeneration and other brain disorders in Doberman pinschers. George Lust at Cornell University is studying genetic roots of hip displaysia in Labrador retrievers.
"We have regions of genes identified, but it's very early," said Lust. "The genome is critical — we need that information to design markers to find candidate genes."
Perhaps some of the best promise is for those with rare diseases that might not normally be the subject of much investigation. Labora, for example, is a very rare and uncurable form of epilepsy. Doctors know about only 200 human cases in the world, but many purebred miniature wirehaired dachshunds suffer a kind of twitching disorder that is a mild form of the human disease. Research to cure the animal may help doctors find a way to treat the human form.
This might all be good news for human patients, but what about dogs?
Brave New Dog World?
For those that are cured and allowed to live like Lancelot, the benefits are obvious. And although one of Lancelot's siblings was euthanized following the vision research, scientists claim such measures should be rare.
"All of this work can be done from blood samples," said Kirkness. "This is taken from dogs just the way it is taken from people."
He points out that the number of dogs used in research pales in comparison with the number abandoned and euthanized. A study from the American Society for the Prevention of Cruelty to Animals estimated that about 100,000 dogs are used in medical research every year, while 2 million to 3 million are euthanized by shelters.
For better or for worse, Chader also believes the genetic work could help breeders create the "perfect dog."
By identifying problematic genes, breeders will be able to selectively breed them out or even treat dogs with the condition using gene therapy (although this would likely be prohibitively expensive).
"Everything we shy away from in humans — breeding for smarter, taller kids, choosing eye and hair color — we may not do that in people," said Chader. "But we will in dogs."
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