First human trials of embryonic stem cell-based therapies head to …

On January 3, stem cell therapeutics company Advanced Cell Technology (ACT) announced it had received approval from the US Food and Drug Administration to kick off a Phase I/II clinical trial using the company's retinal epithelial cells (RPE). The cells would be used to treat dry age-related macular degeneration (AMD), a progressive vision impairment affecting some 15 million Americans.

It's always good news for a company when the FDA clears an investigational new drug application. What made this particular announcement interesting was the source of the biologic agent: ACT would be treating a dozen patients with between 50,000 and 200,000 cells derived from human embryonic stem cells. These cells will be injected into the subretinal space of patients' eyes, where it is hoped they will "restore visual acuity" by activating dormant photoreceptors, says CEO Gary Rabin.

Preclinical data, Rabin says, look promising. "In our animal studies, we saw our ability to take rats and mice that were otherwise on their way to being completely blind, and reverse their vision loss to the point that we had restored their visual acuity to 70% that of a healthy animal," he says.

The question is, will positive outcomes in animal models translate to human subjects? And more importantly, is the therapy safe?

ACT's AMD trial actually is the third hESC-based trial approved by the FDA. In November, FDA green-lit the company's IND for using its RPE cells to treat Stargardts Disease, a genetic form of juvenile macular degeneration. The company hopes to begin both trials in May, Rabin says. But Geron Corp. has the honor of actually initiating the first study, officially enrolling its first patient in a trial to treat spinal cord injury with hESC-derived oligodendrocyte progenitor cells (GRNOPC1) in October.

"I think that is a momentous milestone," says George Daley, Director of the Stem Cell Transplantation Program at Children's Hospital Boston and Executive Committee member of the Harvard Stem Cell Institute, "because it required enormous, I would even say Herculean effort to qualify those cells to achieve a certain level of comfort that they were safe enough to put into humans."

And it is one, Daley adds, that should "pave the way for others to follow."

The Geron trial, with sites in California, Georgia, Illinois, and Pennsylvania, involves up to 10 patients with so-called mid-thoracic "complete" spinal cord injuries paraplegic injuries induced by a fall or car accident, for instance. The cells will be administered in a single injection of 2 million cells within one to two weeks of injury, under general anesthesia, by a trained neurosurgeon using a custom-built "syringe positioning device," says Jane Lebkowski, CSO of the company's regenerative medicine section.

Geron's preclinical data suggest the cells have three separate, yet interrelated activities, Lebkowski says: producing neurotrophic factors that can prevent cell death and induce cell growth; remyelinating myelin-depleted cells in the damaged area; and inducing vascularization. "I don't think it's any one mechanism," Lebkowski says; all three seemingly contribute to the cells' therapeutic effect.

How much repair these cells can produce, of course, is an open question. According to Aileen Anderson, a spinal cord injury expert at the University of California, Irvine, patients are likely to see at best modest gains. It's not like paraplegics are likely to simply get up and start walking, she says. But the value of even subtle improvement should not be underestimated, she explains. Restoration of trunk stability or bladder control in a paraplegic, for instance, can make patients more self-sufficient, restore dignity, and decrease medical costs (for instance, by reducing pressure sores and other complications). The same is true for blindness. "There's a big difference between being able to see shadow and not," she says.

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First human trials of embryonic stem cell-based therapies head to ...