Stem cell trial sets sight on blindness

About 10 million Americans suffer some degree of vision loss caused by age-related macular degeneration, and that figure is expected to grow as more baby boomers become senior citizens. There is no cure for the disease, but last week the U.S. Food and Drug Administration gave a green light to an unusual clinical trial that seeks to restore patients' sight by employing human embryonic stem cells.

None of the stem cells will be injected into patients; instead, they are grown into another kind of cell that will be delivered to the back of the eye, where the retina is damaged by the disease. The hope is that the cells will help repair the damaged retinal tissue.

The company behind the trial, Santa Monica-based Advanced Cell Technology Inc., developed the therapy to treat Stargardt's macular dystrophy, a rare childhood version of macular degeneration that affects about 1 in 10,000 kids. The FDA gave the company permission to test the therapy in Stargardt's patients in November. However, if they work, the cells would have a much bigger effect as a treatment for age-related macular degeneration.

Here's a closer look at the disease and the new therapy.


What is age-related macular degeneration?

Age-related macular degeneration is the leading cause of vision impairment and blindness among people who are 65 and older, says Dr. Jose Pulido, an ophthalmologist at the Mayo Clinic in Rochester, Minn. The dry version of the disease begins with tiny deposits of fat and protein -- called drusen -- that appear in the center of the retina, called the macula. As the deposits grow in number and size over the course of years, things begin to look blurry in the center of a person's field of vision. As the disease worsens, the blurriness may progress to a blind spot.


What causes it?

The main problem is that light-sensing cells in the macula, called photoreceptors, slowly break down. This is thought to be caused by the loss of another population of cells, called retinal pigment epithelial (RPE) cells, which support the photoreceptors in a number of ways.

Among other things, the RPE cells release growth factors important for photoreceptors to thrive. "The RPE are also the garbage trucks of the retina," removing toxic byproducts that the retina makes as it performs its light-sensing function, says Stephen Rose, chief research officer for the Foundation Fighting Blindness, a fundraising organization based in Columbia, Md.

Dry age-related macular degeneration can also progress into wet age-related macular degeneration, in which blood vessels grow abnormally and leak fluid into the macula. It's a much more aggressive form of the disease, but it's also more treatable.


How can human embryonic stem cells help?

The stem cells are grown into healthy replacement RPE cells and injected into the retina, says Gary Rabin, Advanced Cell Technology's chief executive. The company hopes the lab-grown cells will replace the dying RPE cells and keep vision intact -- or even restore it to some degree.

"We've had incredible success with this in animal studies," Rabin says. A study published in the journal Stem Cells found that the RPE cells restored eye function in sick mice and rats to "near-normal levels," and another study in Cloning and Stem Cells reported that the treatment improved vision in affected rats until it was 70% as good as that of healthy animals.

Of course, success in animal studies doesn't always translate to humans. In addition, the eyes of people in their 50s and 60s likely present "a very different milieu for the RPE cells to try to hook onto," Pulido says.

Rose adds that the treatment, if it works, wouldn't amount to a cure because it doesn't address the reason why RPE cells deteriorate in the first place. But it would buy time for patients, delaying vision loss for perhaps years. "That's huge," he says.


What will the new trial assess?

The FDA granted permission to conduct a Phase I/II clinical trial, which is essentially a safety trial, that will involve a dozen patients. The first patients will get a very low "dose" of cells -- 50,000 -- and will be monitored for any untoward effects.

"If there are no safety issues after three-ish months, we will increase the dose [to a level where we] hope to see efficacy," Rabin says. "We anticipate that the photoreceptor cells will awaken and that there will be a gradual increase in visual acuity over time." For now, the protocol calls for a one-time treatment of up to 200,000 cells.


Aren't there ethical concerns about using human embryonic stem cells?

Generally speaking, many people are troubled by research involving human embryonic stem cells because they are typically made by dismantling -- and thus destroying -- embryos that are a few days old.

Advanced Cell Technology uses a proprietary technique to extract a single cell from a young embryo, allowing the rest to remain intact and develop normally, Rabin says. A similar method is routinely used to biopsy embryos for pre-implantation genetic diagnosis, in which embryos created through in vitro fertilization are scanned for genetic disorders before being transferred to a uterus.

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