The Food and Drug Administration cleared the way on Friday for California biotech firm Geron (GERN) to begin human clinical trials of its experimental embryonic stem cell-based therapy to heal spinal cord injuries in certain paraplegic patients. Geron claims this is the first such trial in humans.
The FDA had placed a clinical hold on the drug due to safety concerns: A preclinical animal study showed a higher frequency of small cysts within the spinal cord injury sites injected with Geron's treatment. But as Geron developed new molecular markers and procedures to minimize such risks, it asked for the FDA to lift the clinical hold, which it did this week.
Geron hopes to start the human trial this quarter. It plans to recruit eight to 10 spinal-cord injury patients with complete impairment, meaning they have no motor or sensory function in the effected areas, and whose injuries are in the middle vertebrae. Patients will be injected with a low dose of the drug seven to 14 days after their injuries.
The therapy's name is a mouthful: Geron's human embryonic stem cell (hESC)-Derived Oligodendrocyte Progenitor Cells, or GRNOPC1.
Repairing the Insulation So Nerves Stop Short-Circuiting
Stem cells are a self-renewing source of unspecialized cells that can develop into specialized, functioning cells to replace cells damaged due to injury or disease. And human embryonic stem cells are nature's master stem cells, Geron says. Geron uses hESCs derived from donated surplus embryos originally created as part of in vitro fertilization procedures. (While all the embryos used would otherwise have been destroyed, this is still a politically and ethically charged issue.)
The GRNOPC1 therapy consists of living cells containing precursors to oligodendrocytes, which are naturally occurring cells in the nervous system that have several functions. Among the main functions of oligodendrocytes is the production of myelin -- an important nerve-insulating layer that enables the efficient conduction of nerve impulses -- essentially, the nervous system's equivalent of the electrical wire insulation that prevents short circuits.
This is important because most human spinal cord injuries are contusions (bruises) rather that the actual severing of the spinal cord. These injuries cause severe inflammation that is particularly damaging to the oligodendrocytes in the spinal cord, resulting in the paralysis of those patients.
In preclinical studies, when GRNOPC1 was injected into the injury sites of spinal cord-injured animals, it matured into functional oligodendrocytes, and the treated animals regained improved movement within three to four weeks. Geron's ultimate goal for GRNOPC1 is to achieve spinal cord repair in humans.
Testing for Safety First, Efficacy Second
But the goal of this early-stage trial is primarily to check for the safety of the drug. It's possible, however, that even at these low doses, patients may experience improved movement or sensation, Geron's President and CEO Thomas Okarma said during a conference call. Geron will follow the patients closely for one year to assess the treatment's safety and tolerability, and will continue to monitor the patients for 15 years.
Once the drug's safety has been determined, Geron plans to seek FDA approval to increase the dose of GRNOPC1 to find optimal efficacy, as well as expand the patient base.
In addition to spinal cord injuries, GRNOPC1 may have therapeutic benefit in treating other central nervous system problems. "[W]e are now formally exploring the utility of GRNOPC1 in other degenerative CNS disorders including Alzheimer's, multiple sclerosis and Canavan disease," Okarma said in a statement.
Geron shares soared some 15% in Friday's trading. But as anyone who follows the biotech sector knows, these are highly volatile stocks. And that's particularly true for small companies whose key therapies are in early stages of testing -- like Geron.
Want to succeed? Then you need goals!View Course »