On Monday, doctors at Stanford Hospital and Santa Clara Valley Medical Center became the third group certified to participate in a nationwide trial of embryonic stem cell therapy for patients paralyzed by spinal cord injury.
Funded and run by Geron, a Menlo Park-based biopharmaceutical company, this is the first clinical trial in the world of human embryonic stem cell therapy. Certified by the FDA for testing on 10 patients, the phase-one study aims to test the safety of this treatment.
Stanford’s involvement began in 2007, when Geron contacted Gary Steinberg, chair of the Department of Neurosurgery.
“They contacted me because of my interest and involvement in stem cell therapy for neurologic diseases,” Steinberg said. “I’ve been involved for a long time, both in the laboratory and clinically.”
“At the microscopic level, what was happening to the spinal cords [in injured patients] was the axons—the cables running past the injury—were still intact, but the lining, the insulation of the nerve cells, had died,” said Marco Lee, professor of neurosurgery. “The thesis is, can we replace the cells that had died which were responsible for remyelinating—that is, relining—the neurons?”
The theory for the trials comes from successful experiments done at UC-Irvine that delivered a similar treatment to rodents with spinal cord injuries.
After Valley Medical Center identifies and pre-screens a patient, Geron will deliver embryonic stem cells to Stanford, where they will be prepared and checked for viability and stability. The actual injection of the cells will take place at Valley Medical Center and will be performed by Steinberg and Lee.
“The procedure is to deliver an embryonic derived cell. It’s not actually the embryonic cell itself, and that’s a confusing point sometimes,” Steinberg said. “These are human embryonic stem cell-derived oligodendrocyte progenitors, which are the cells that produce myelin, the insulation of nerves.”
The other two approved sites in the country—Northwestern and the Shepherd Center in Atlanta—have already injected one patient with the stem cells and screened another. Geron has proposed a total of seven sites. Ultimately, the distribution of the 10 patients around the country will depend on subject availability.
“The patients will be enrolled by different sites,” Steinberg said. “There’s not a limit necessarily to any one site enrolling more than one, but it’s a rare disease. It’s a rare injury. So it’s unpredictable where the patients will be enrolled depending on which sites are up and going.”
Researchers are also facing the challenge of retaining the subjects they can find. Patients are physically disabled—most have suffered injuries from car accidents, falls or sports—but mentally stable.
“Like Christopher Reed, they have all their mind there,” Lee said. “When you run a trial like that, it’s actually an important consideration. You need motivated patients to stick with you. A trial is not simply injecting stem cells. It’s everything that comes after that.”
The first goal of this trial is not efficacy but rather safety—that is, the determination of the treatment’s safety in humans before it can be tested in a larger group.
“Phase one in any trial…is always about safety,” Lee said. “But, having said that, we’re obviously not going to run a trial and just look at safety, even though that’s our primary aim. So we have secondary aims…which [are] to see whether patients have recovery.”
Their recoveries will be measured with physical and psychological assessments in the year after the injection, as well as continuing follow-up for 15 years after treatment.
Ultimately, if the phase-one trial proves the safety of the treatment, phase-two and -three trials could test its efficacy, especially in a greater number of patients with less severe spinal cord damage.
“The greatest benefit would come to people with mild weakness. It could convert them back to normal,” Lee said. “Or they have severe weakness, but you could convert them back to mild weakness.”