Cautious Optimism for the First Stem-Cell Human Trial

It was nearly a decade in the making, but the first human trial using embryonic stem cells was approved on Friday.

The trial, which will test a stem-cell-based treatment for spinal-cord injury, will begin later this summer and will use cells generated by Geron Corp. The approval marks the first time human stem cells, extracted and grown from embryos, will be transplanted into patients. Adult stem cells, which are present in many types of tissue, have been used in treatments for years — the most common being bone-marrow transplants in cancer care — but an embryonic study is a whole new thing. There's a good reason it's being greeted with so much excitement. (See the top 10 medical breakthroughs of 2008.)

Scientists believe that embryonic stem cells are more versatile than adult cells in generating the more than 200 different tissue types in the body. The need for healthy new cells is particularly acute in the case of spinal-cord injury, because once central-nervous-system tissue is destroyed, it does not regenerate — not in any significant way, at least. The Geron team began its work with what is known as a presidential stem-cell line — stem cells derived from discarded in vitro–fertilization embryos that already existed in 2001 when then President Bush decided to prohibit the use of federal funds to pursue human embryonic-stem-cell work. At the time, fewer than two dozen of these stem-cell lines were of good enough quality to use as a basis for human treatments.

The therapy revolves around coaxing the stem cells to develop into a type of cell known as an oligodendrocyte, which in turn gives rise to critical insulation and growth factors that can repair neurons damaged by a trauma to the spinal cord. Geron has named its version GRNOPC1. By having more of these cells around the spinal cord, more nerves might be repaired and can then potentially re-establish proper connections. Simply by working with the GRNOPC1 cells, Geron scientists have learned more about how they operate, which will expand their understanding of how the central nervous system might be healed. Says Geron's president and CEO, Dr. Thomas Okarma: "They make dozens of factors that can stimulate nerve function, growth and regeneration." (Read "Scientists Reach Stem-Cell Milestone.")

The trial will enroll patients with injury to the thoracic region, high in the spinal cord between the third and 10th vertebrae. Doctors will be trained to inject the cell treatment at specific locations, where the cells will remain to do their nerve-nurturing work. "I think it's incredibly exciting," says Dr. Susan Fisher, a stem-cell scientist and a professor of obstetrics, gynecology and reproductive science at University of California, San Francisco. "This really provides a blueprint for how to do these sorts of trials. It really proves the principle that these sorts of human embryonic-stem-cell therapies can survive the FDA approval process."

And that process wasn't such an easy hurdle to overcome. Because no one has used embryonic stem cells or the cells derived from them in people before, the FDA was particularly cautious. The trial that it approved is what's known as a Phase 1. It will involve no more than a dozen patients and is not designed to test the effectiveness of the cells. Rather, it will simply monitor the safety of inserting them into people. The researchers will be looking for whether the cells cause tumors, trigger an immune response or start to migrate away from the spinal-cord area. "There are certainly unknowns that we can't predict," says Dr. David Scadden, co-director of the Harvard Stem Cell Institute. "We don't know whether or not these cells might grow abnormally in a person. We don't know if things might occur just by these cells being present that could result in an outcome we don't want. This really is a first go, with a lot on the line."

Dr. Ronald Crystal, chairman of the department of genetic medicine at New York–Presbyterian Hospital/Weill Cornell Medical College, knows those stakes all too well. He is a veteran of the last revolution in medical technology, gene therapy, which, after some hyped expectations in the 1990s, fell into disfavor after some unsuccessful trials. Crystal is cautiously optimistic about the potential for this trial to open the door to future stem-cell therapies. "I think this is a very positive start, but the expectations and hype I see around stem-cell therapies are the same that I saw around gene therapy. We just have to remember that these take a long time to develop. But you will never know if they work unless you study them in humans, so this is an important first step."

Read "Stem Cells: The Hope and the Hype."

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