The Food and Drug Administration has cleared Geron, a stem cell company based in Menlo Park, CA, to move forward with clinical tests of its experimental cell therapy for spinal cord injury, which is derived from embryonic stem cells. The company, which has been working on cell based therapies for the last decade, first won permission to begin clinical testing in January of 2009. But the trials were put on hold last August due to new safety concerns from animal tests. The clinical trial marks the first human tests of a therapy derived from embryonic stem cells.

The cell therapy, called GRNOPC1, is made by transforming embryonic stem cells into oligodendrocytes--a type of brain cell that wraps itself around neurons, forming a fatty insulation layer that allows electrical messages to be conducted throughout the nervous system. In many spinal-cord injuries, these cells are damaged, but the underlying nerve cells remain intact. The new cells are then injected into the site of the injury, coating exposed nerves and restoring communication to the nervous system.

As I noted in a previous post:

Scientists published the results of a successful study testing the therapy in animals in 2005, showing that paralyzed rats injected with the cells were able to walk again. Since then, Geron has been conducting numerous studies intended to show the safety of the cell-based therapy, as well as developing production methods that would make the cells as easy to use as more traditional treatments. Geron researchers have also developed a way to reliably freeze and thaw brain cells, so that they can be manufactured in a central location, and then shipped to the hospitals where they will be used.

According to a statement from Geron:

The clinical hold was placed following results from a single preclinical animal study in which Geron observed a higher frequency of small cysts within the injury site in the spinal cord of animals injected with GRNOPC1 than had previously been noted in numerous foregoing studies. In response to those results, Geron developed new markers and assays as additional release specifications for GRNOPC1. The company completed an additional confirmatory preclinical animal study to test the new markers and assays, and subsequently submitted a request to the FDA for the clinical hold to be lifted.

Advanced Cell Technology, a stem cell company based in Marlborough, MA, hopes to follow Geron. The company announced this week that it has submitted new materials to the FDA in regards to its application, first filed in November, to begin clinical trials of a cell therapy for patients with Stargardt's Macular Dystrophy, an inherited eye disease.

The National Institutes of Health (NIH) announced today that 13 new embryonic stem cell lines are now eligible for federal funding. That means that scientists with NIH grants can study embryonic stem cells derived using newer, more refined methods generally considered to be superior to the older ones. Ninety-six additional lines are also now under review.

"Those were early days in the science of stem cell research, and much has been learned since then," said NIH director Francis Collins in a press conference on Wednesday, referring to the stem cell lines, created before 2001, that had previously been eligible for federal funding. "In the last eight years, hundreds of embryonic stem cell lines have been derived using non-federal funds, many of them carrying more favorable characteristics."

As I wrote in a previous story:

Using only the old lines is like "being required to use Microsoft Word 1998," says Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute, in La Jolla, CA.

The earlier lines were derived using animal products, making them largely unfit for therapeutic use. "There are hundreds of embryonic stem-cell lines out there that have been made under the best conditions, and some of them are patient ready," says John Gearhart, director of the Institute for Regenerative Medicine at the University of Pennsylvania, in Philadelphia. "They have greater utility, performance, and safety than [the Bush-approved] lines."

The announcement follows President Obama's executive order made last March, enabling government support for embryonic stem cell research. That order overturned a previous one by President Bush in 2001, limiting federally-funded research to a set of existing cell lines. The 2001 decree forced scientists who wanted to create and use new stem cell lines, derived from leftover IVF embryos, to garner private funding.

Eleven of the 13 new lines were generated in George Daley's lab at Children's Hospital, in Boston, which used private funding to make them. According to the New York Times, "Dr. Daley said that private financing had been drying up and that he was eager to start research on the now-approved cell lines with the help of his federal grant money." Researchers still cannot derive new lines using federal funds--creating new lines requires the destruction of an embryo.

The first human trial of human embryonic stem cells--involving a treatment of spinal cord injury developed by Geron, a cell therapy company based in Menlo Park, CA--has been put on hold once again. The company says the trial has been halted by the Food and Drug Administration "pending the agency's review of new nonclinical animal study data submitted by the company."

Geron has been working on embryonic stem cells for the last decade and received approval to begin human tests of embryonic stem cells in January 2009. I described the details of the trial and the therapy in a previous blog post:

The trial is limited to eight patients with newly acquired spinal-cord injuries who will receive injections of the cell therapy, called GRNOPC1, within two weeks of their accident. GRNOPC1 is made by transforming embryonic stem cells into oligodendrocytes--a type of brain cell that wraps itself around neurons, forming a fatty insulation layer that allows electrical messages to be conducted throughout the nervous system. In many spinal-cord injuries, these cells are damaged, but the underlying nerve cells remain intact. These cells are then injected into the site of the injury, coating exposed nerves and restoring communication to the nervous system.

Scientists published the results of a successful study testing the therapy in animals in 2005, showing that paralyzed rats injected with the cells were able to walk again. Since then, Geron has been conducting numerous studies intended to show the safety of the cell-based therapy, as well as developing production methods that would make the cells as easy to use as more traditional treatments. Geron researchers have also developed a way to reliably freeze and thaw brain cells, so that they can be manufactured in a central location, and then shipped to the hospitals where they will be used.

Because embryonic-stem-cell-based therapies are so new, the FDA has had trouble deciding how to evaluate new drug applications. (Geron's president and CEO, Thomas Okarma, thought approval was imminent when I spoke with him in 2006. See "Human Tests of Embryonic Stem Cell Treatments Planned.") The initial trial is designed to assess safety, but doctors will also measure its effectiveness, such as improved neuromuscular control or sensation in the trunk or lower extremities.

According to a statement from the company:

Geron has been undertaking studies to enable dose escalation of its spinal cord injury product, and has been investigating application of the product to other neurodegenerative diseases. The company has also been performing additional product characterization and conducting further animal studies. Data from this work has been submitted to the FDA. Geron will work closely with the FDA to facilitate their review of the new data and to release the clinical hold. No patients have yet been treated in this study.