Though a trial in humans is still a few years away, the results mark yet another success for the Foundation Fighting Blindness, a Maryland nonprofit that has distributed $250 million to more than 300 researchers such as Aguirre since 1971.
More than 200 human retinal diseases, including Best disease, are caused by a mutation in a single gene. Yet individually, most of these ailments are rare. Scientists say their research would proceed much more slowly, if at all in some cases, if it were not for support from the foundation.
The organization will hold its annual local fund-raising dinner Tuesday at the Union League. As in other cities, it is called Dining in the Dark, because guests wear blindfolds while eating to get a sense of what blindness is like - with one distinction.
"We get to take our blindfolds off" afterward, said event cochair Brook Lenfest of Haverford. (Lenfest is the son of H.F. "Gerry" Lenfest, an owner of Interstate General Media, which publishes The Inquirer.)
Researchers have used foundation and government funding to chip away at the list of rare, hereditary retinal diseases one by one, with treatments for half a dozen in various stages of development. One of them, Leber congenital amaurosis, has been treated with some success in humans.
Some of the patients were injected at Children's Hospital of Philadelphia in partnership with Penn's Scheie Eye Institute. That team is slated to launch a human trial of another eye ailment, choroideremia, in the first quarter of 2014, said another foundation-funded scientist, Jean Bennett of the Scheie Eye Institute.
With both diseases, the general approach is the same as what Guziewicz, Aguirre, and colleagues used in dogs with Best disease: gene therapy. A surgeon injects the eye with harmless viruses that have been programmed with genetic instructions to compensate for the patient's defective copies.
Ultimately, the goal of many researchers is to develop generic treatments that could be applied to multiple forms of blindness, Bennett said. One such idea, which she and others are studying, is to use a technique called optogenetics - reengineering healthy, non-visual cells so they can detect light.
"Irrespective of what the insult was, you'd harness remaining circuitry in the retina to make that light-sensitive," she said.
In the meantime, the dog has been an invaluable guide. At least 20 human eye diseases are known to have a canine equivalent. Aguirre and colleagues are working on four of them, with others to follow.
For the research on Best disease, he and Guziewicz collaborated with Samuel G. Jacobson and Artur V. Cideciyan at the Scheie Eye Institute, along with William Hauswirth and Alfred S. Lewin at the University of Florida.
Once an egg-yolk lesion degenerates into the scrambled-egg appearance, as it did in the first dog Aguirre diagnosed, vision is substantially impaired. But in the study, the researchers injected dogs with the therapeutic genes while the lesions were still intact, and within eight to 12 weeks, the blobs disappeared from the area immediately surrounding the injection sites.
Aguirre said they had followed the dogs in the study for little more than a year, so further observation was needed.
"Perhaps after two years, it stops working," he said, expressing the sort of caution common in many scientists. "We don't know."
Yet the success to date has team members sounding practically giddy by the standards of their profession.
Asked about the Best-disease results, Guziewicz at first called them "promising."
Aguirre, sitting at her side, corrected her.
"No, I wouldn't use promising," he said. "Really, really great."
She quickly agreed.
"It's working," she said. "It's really working."
Contact Tom Avril at 215-854-2430 or firstname.lastname@example.org.