Geron, a California company developing therapies derived from embryonic stem cells, announced on Monday that the first patient has been treated in its landmark trial for spinal cord injury. The therapy, which involves injecting differentiated neural cells into the injury site, is the first such treatment to be tested in humans. Other experimental stem cell therapies involve adult stem cells or cells derived from fetuses.

Geron first garnered approval for the tests from the U.S. Food and Drug Administration in January of 2009. But that approval was put on hold several months later due to new safety concerns from animal tests. Because cells can behave unpredictably, regulators want to make sure the transplanted cells don't develop into teratomas, a type of tumor associated with the injection of embryonic stem cells.The FDA gave permission to resume testing in July, after another round of animal safety tests. This early stage trial is designed to assess the safety of the therapy in humans and will involve a small number of patients with new injuries; the treatment must be delivered within 14 days of the injury.

The cell therapy 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. These cells are often damaged in spinal cord injury, while the underlying nerve cells remain intact. When the new cells are injected into the site of the injury in animals, they coat exposed nerves and restore communication to the nervous system.

In 2005, Hans Keirstead and collaborators at the University of California, Irvine, showed 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.

The first patient in the study was enrolled at the Shepherd Center, a private, not-for-profit rehabilitation hospital in Atlanta, Georgia. It is one of seven potential sites in the United States that may enroll patients in the clinical trial. According to Geron,

Northwestern Medicine in Chicago, IL is also open for patient enrollment. As additional trial sites come online and are ready to enroll patients, they will be listed on the Patient Information pages of Geron's website and on the NIH clinical trials registry, ClinicalTrials.gov.

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 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.