Experimental treatment for a congenital eye disease has raised hopes for young brothers Casey and Alex Catalan, and the procedures at Oregon Health & Science University in Portland reflect renewed interest in gene therapy.
When 11-year-old Casey Catalan goes on a walk in his Bellingham neighborhood, he hustles to be home before twilight. Once the sun fades, so does Casey’s vision, because of a congenital eye disease.
“I can’t see anything once the light is out,” Casey said. “It’s like being blind.”
Casey’s disease, which eventually also could rob him of daylight sight, is caused by a rare genetic malfunction inside his retina, a malfunction shared with his younger brother, 6-year-old Alex. Neither the brothers’ parents nor their younger sister have the disorder.
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For decades, doctors have considered this eye disease — Leber congenital amaurosis — to be incurable. For Casey and Alex Catalan, there’s fresh reason to hope as the two boys recently have undergone experimental treatment at Oregon Health & Science University in Portland that introduced healthy genes.
This trial reflects renewed interest in gene therapy, which was launched 20 years ago in experiments funded through the National Institutes of Health. Since then, there have been plenty of setbacks, and no gene treatments have gained final federal approval for use in the United States.
But dozens of trials are now under way that attempt to introduce beneficial genes that can replace faulty genes, or stimulate the growth of cells that will help fight a disease. Researchers, for example, have injected genes into brain cells to boost production of dopamine that combats Parkinson’s disease.
The trial involving the Catalan brothers is funded by Florida-based Applied Genetics Technology, which hopes to establish that this gene — introduced to the retina with the aid of a benign virus — can slow or halt the advance of the disease and eventually improve a patient’s sight. Each patient receives the gene in the retina of one eye, with the other serving as a control to monitor the effectiveness of treatment.
This specific gene treatment has a chance of helping only about 300 of the roughly 3,000 Americans who suffer from Leber congenital amaurosis, and the two Catalan brothers were fortunate to fall within that small group.
If successful, the trials could spur a wider range of gene-therapy research to treat more common eye diseases such as macular degeneration that may be influenced by a person’s genetic makeup, or other diseases caused by a specific genetic mutation.
Researchers were encouraged by initial tests on more than 60 Briards, herding dogs that suffer from the same genetic eye disorder.
The Food and Drug Administration (FDA) then approved introduction of the genes in the retinas of three patients, whose sight, according to 2008 findings reported in the Proceeding of the National Academy of Sciences, did improve.
“All the evidence that has been published in the literature so far would support the belief that you will have long-term benefits from this [treatment],” said Jeff Chulay chief medical director for Applied Genetics.
First moment of hope
Casey’s mother, Christine Harris, said it was a struggle to determine just what was wrong with her son’s eyesight. When he was a toddler, she noticed that he stumbled as the light dimmed. Eventually, after extensive testing, she was told Casey had night blindness as a result of a rare genetic disorder.
Initially, there appeared to be no possibility of treatment. That changed in January 2006, when Harris got a call at her workplace at Costco Wholesale from Dr. Richard Weleber, an ophthalmologist at the Oregon university.
“They had identified the gene mutation, and he was ecstatic,” Harris recalls. “It was the first real moment of positive hope because this was the only one that was headed toward treatment.”
This summer, Alex and Casey became the youngest of five patients approved by the FDA to participate in the Applied Genetics trial, with the operations to be performed at the Casey Eye Institute at the Portland university’s medical campus.
Unlike the adults in the trial, the two brothers still retain most of their daylight eyesight. So the main hope for the retina treatment would be to forestall the rapid degeneration of their eyesight in the treated retina, which otherwise would likely occur in their teenage years.
Younger Alex received the gene transplant in July and bounced right back. That helped reassure Casey as he prepped last week for a morning surgery. Still, he was a bit on edge.
“The thought of having a needle jabbed into your eye is not a good thought,” Casey said. “Not at all.”
An hourlong surgery
Casey’s surgery took about an hour as Dr. J. Timothy Stout, peering through a microscope, manipulated extremely thin tweezers and other surgical tools.
Most of the operation involved the same procedures Stout had performed thousands of times to repair detached retinas. He used his tools to create three tiny holes that would aid him in shining light into the eye, removing the eye’s vitreous fluid and replacing it with a saline solution, and accessing the retina.
Once those holes were done, Stout and his surgical team turned to the special task of this eye operation. Stepping away from the sedated Casey, he drew a syringe full of the virus carrying the gene and then injected the fluid through one of the holes and into a narrow area just underneath the retina.
“You are about 60 millionths of a meter away from this really vascular area that will bleed like crazy,” Stout said. “That’s the dodgy bit, you want to make sure you go far enough — but not too far.”
The fluid formed a tiny blister beneath the retina, which would subside in about a day.
Stout stitched up the three holes, then Casey was wheeled out of the operating room to a recovery room, and he was released from the hospital later that day.
In the years ahead, Casey’s and Alex’s eyes will be closely monitored. If the brother’s treated eyes remain stable, Stout says he would hope the trial eventually could be modified to give the gene to the untreated eye as well.
“What we do on that day, that call will be made by the FDA,” Stout said.
Hal Bernton: 206-464-2581 or firstname.lastname@example.org