MENLO PARK, Calif., Jan. 23 -- The FDA has cleared the way for the first clinical trial of a human embryonic stem cell-based therapy, one that is aimed at remyelinating injured spinal cords, Geron announced here.
The multicenter phase I trial is planned to begin this summer, Geron said. Geron's embryonic stem cell lines were included among those approved for use in federally funded research under former President George W. Bush's order limiting such studies.
Eight to 10 patients with complete, grade A spinal cord injuries will be given single injections of oligodendrocyte progenitor cells derived from human embryonic stem cells.
Rodent studies have indicated that the cells cause spinal nerve fibers to remyelinate after subacute injuries, restoring a measure of neuromotor and sensory function, said Thomas Okarma, Ph.D., M.D., Geron's president and CEO, at a press briefing.
The cells also differentiate into neuronal cell types and cause release of neurotrophic factors thought to promote restoration of spinal function, he said.
The cells, dubbed GRNOPC1, will be injected directly into the lesion site within one to two weeks of injury. Because the injections must be precisely controlled, specially trained spinal surgeons will perform the procedure, using a syringe positioning device that attaches to the frame of the operating room table.
As with any phase I trial, the primary endpoint is safety, but neurological and motor function will also be evaluated for one year after treatment. Monitoring is expected to continue for a total of 15 years, said Dr. Okarma.
Although the point of embryonic stem cell-based therapies is to be nonimmunogenic, patients in the Geron trial will be given low-dose tacrolimus (Prograf) for 60 days after the injections.
Dr. Okarma said that the risk of rejection was small in any case, not only because of the cells' lack of immunogenicity, but also because the central nervous system is immune-privileged.
Nevertheless, he said, the low-dose tacrolimus offers an added measure of safety.
Tacrolimus has shown some ability on its own to restore spinal cord function after injury in rat models. Dr. Okarma said this effect should not confound the trial's efficacy findings because of the low doses and short duration of treatment.
To qualify for inclusion, patients must have a contusional injury to the thoracic spine with complete loss of locomotor and sensory activity below the injury site.
The spinal cord must not have been severed, as the therapy is not believed to be capable of regrowing or reconnecting nerve cell axons after they have been cut.
Geron said it conducted 24 in vivo studies with mice and rats to establish that the oligodendrocyte progenitors would not induce teratoma formation.
These studies also showed that other potential adverse effects, such as allodynia, immunogenic responses, and cell migration out of the central nervous system, were not a significant risk.
The animal experiments also showed that locomotor function could be partially restored after spinal cord injury that, in untreated animals, caused complete and permanent paralysis.
Dr. Okarma said it would take about eight to 10 months to enroll all the patients in the trial. Before patients may be included, surgeons at the clinical sites must receive training in administering the GRNOPC1 cells. Institutional review board approvals at each site also must be secured.
He said future trials may address cervical injuries as well as higher doses of the oligodendrocyte progenitors.
Press reports immediately suggested that the trial's approval was triggered by the new administration in Washington. During the presidential campaign, Barack Obama promised a friendlier attitude toward research with embryonic stem cells.
But Dr. Okarma said he was not aware of politics playing a role in the trial's approval. He said the company had been making steady progress with the FDA over a period of seven months.
President Obama was expected to relax or rescind the order shortly after taking office, but no announcement has yet been made.