The first clinical trial of cells derived from human embryonic stem cells began in October 2010 in a paralyzed patient at the Shepherd Center in Atlanta. Recently, Stanford University School of Medicine and Santa Clara Valley Medical Center (SCVMC) became the third site to participate in the trial, which will enroll up to 10 patients with spinal cord injuries at up to 7 institutions nationwide.
The FDA-approved, phase-1 trial is meant to test only the safety of the cells, which can develop into neural support cells called oligodendrocytes found in the brain and central nervous system. If the investigational treatment is shown to be safe for use in humans, larger clinical trials will be designed to test whether the cells are better able than conventional treatments to improve a patient’s condition.
Because the cells must be administered within 2 weeks of the initial spinal cord injury, the trial is open only to those with very recent trauma and only upon physician referral.
The trial is run by Menlo Park-based Geron Corp., which developed and manufactures the cells for testing. The cells for this portion of the trial will be thawed and prepared at Stanford, and the surgery to implant the cells will take place at Valley Medical Center, which is one of the largest referral centers for acute spinal cord injury and rehabilitation on the West Coast. Physicians certified to conduct the procedure include Stanford neurosurgeons Gary Steinberg, MD, PhD (pictured), and Marco Lee, MD, PhD.
Steinberg is the principal investigator of the Stanford/SCVMC portion of the trial. He has been researching the use of stem cells in models of neurological injury or illness for more than a decade, and he heads a team of Stanford researchers that received a $20 million grant from the California Institute for Regenerative Medicine to study how neural stem cells could be used to treat people with ischemic stroke — a condition that occurs when a portion of the brain is deprived of blood flow.
“Until recently, we have not had any hope of restoring neurological function in people with spinal cord injury or stroke, or those with brain tumors or Alzheimer’s disease,” said Steinberg, the Bernard and Ronni Lacroute-William Randolph Hearst Professor in Neurosurgery and Neurosciences. “But now we’re moving stem cell therapy into the clinic, which I feel is a tremendously important step. People are not mice or rats, and we can learn so much from clinical trials that we can never learn by studying animals.”
Steinberg and Stanford have a strong background in stem cell biology, while Santa Clara Valley Medical Center has the patients and an extensive rehabilitation facility for spinal cord injuries.
“Valley Medical Center treats more than 150 people a year with severe spinal cord trauma, many of which are caused by motor vehicle accidents, falls, and sports injuries. Patients with this kind of injury are very familiar to our staff, and we have the training and experience to help them through their recovery,” said Stephen McKenna, MD, chief of SCVMC’s Rehabilitation Trauma Center. “By collaborating with Stanford, we can evaluate and enroll patients in the trial without altering their normal referral pathway.”
The strict timeline of the trial makes it impossible to predict in advance how many, if any, patients may be treated at each of the participating sites. Essentially, each site will prepare for the possibility that a person with a recent spinal cord trauma that meets the criteria will be referred to their center and will agree to participate in the trial. To be eligible, patients must have non-penetrating damage to a specific region of their thoracic spine — an area roughly from the top of the shoulder blades to the bottom of the rib cage. The damage must cause complete paraplegia, meaning that they have normal sensation or movement to the level of the hands, but neither from the trunk to the toes.
Researchers at Geron collaborated with Hans Keirstead’s laboratory at University of California (UC)-Irvine to develop a way to coax human embryonic stem cells to become a mixture of cells that include oligodendrocyte precursors. Oligodendrocytes are cells in the brain and the central nervous system that wrap nerve cells with an insulating material called myelin. This myelin sheath is necessary for the transmission of the electric signals along the spinal cord that trigger muscles to move, and relay our sense of touch and temperature. Damage to this sheath caused by trauma is a common cause of paralysis.
During the procedure, the neurosurgeon will apply about 2 million of the special cells (called GRNOPC1) directly into the injured area of the enrolled patient’s spinal cord. Following the surgery at Santa Clara Valley Medical Center, the patient will enter an intensive inpatient rehabilitation program under the supervision of specialists in spinal cord injury medicine. Researchers will then monitor the patient to confirm that the cells are safe for use in humans.
Although the primary endpoint of this phase-1 trial is simply to assess the safety of the protocol, animal studies suggest that the oligodendrocyte precursors will migrate throughout the site of damage and mature into myelin-producing cells to re-insulate the affected neurons.
The researchers don’t expect a cure for paralysis. It’s possible, though, that subsequent larger clinical trials may demonstrate an improvement in function that may one day allow patients to regain some mobility or feeling, or to have better control over their bladder or bowel function.
“These are the kind of things that matter to patients,” said McKenna. “People with this type of injury don’t expect to get up and walk. But even small improvements in function can greatly impact their lives and lead them to a more meaningful recovery.”
The oligodendrocyte precursors (GRNOPC1) are produced from stem cells that were originally derived from a single embryo created through in vitro fertilization. Such excess embryos are usually discarded when no longer needed, but can be donated for research by the parents under informed consent. The U.S. Food and Drug Administration approved the human clinical trial in 2009 after extensive tests in laboratory animals. The first patient was treated in October at the Shepherd Center in Atlanta; Northwestern University in Chicago is also open for patient enrollment. Other participating sites have not yet been identified.
Illustration: Stanford University School of Medicine.
Stanford University School of Medicine News (01/24/11)
The Stanford Daily (01/28/11)
Clinical Trial: Safety Study of GRNOPC1 in Spinal Cord Injury (Geron Corporation)