Geron Corporation (Nasdaq:GERN) today announced the publication of data showing that oligodendrocyte progenitor cells (OPCs) derived from human embryonic stem cells (hESCs), when transplanted into a rodent model of cervical spinal cord injury, reduced tissue damage within the lesion and improved recovery of locomotor function. These data provide preclinical proof-of-concept for the use of GRNOPC1, Geron’s hESC-derived oligodendrocyte progenitor product, in patients with cervical spinal cord injuries. Over half of the 11,000 human spinal cord injuries that are sustained in the U.S. annually are in the cervical region.
The study was authored by Geron collaborator Dr. Hans S. Keirstead and colleagues at the Reeve-Irvine Research Center and the Sue & Bill Gross Stem Cell Research Center at the University of California at Irvine. The paper was published online in advance of print in the journal Stem Cells. The abstract of the publication is available at http://www3.interscience.wiley.com/journal/122666108/abstract.
Oligodendrocytes have two main functions in the spinal cord; they produce the myelin that wraps around nerve fibers to enable electrical impulse conduction and they produce other molecules (neurotrophic factors) that help to maintain nerve cells. In spinal cord injury oligodendrocytes are lost, resulting in the loss of myelin and death of nerve cells that can cause paralysis below the injury. The present study, conducted in a cervical model of spinal cord injury, adds to previous work in a thoracic model, which has demonstrated that injection of hESC-derived OPCs into the site of injury improved locomotor function with evidence of remyelination of nerve fibers.
The cervical injury model used in this study induced widespread tissue loss resulting in a cavity in the spinal cord. In contrast, there was no cavity in the spinal cord of the rodents that had been injected with hESC-derived OPCs seven days after injury, and the transplant area contained human oligodendrocytes. Further analysis of the injury sites revealed there were significantly more normally myelinated neurons, fewer demyelinated neurons, and importantly, a greater number of preserved motor neurons compared to controls. These data provide in vivo evidence that hESC-derived OPCs may protect the spinal cord from tissue damage induced by injury in addition to having a remyelinating function. Along with these observations was noted a decrease in genes associated with tissue damage and inflammation suggestive of a mechanism in which hESC-OPCs are exerting their tissue-sparing effect.
Critically, the preservation of motor neurons within the spinal cord was shown to correlate with functional recovery. In the cervical injury model forelimb function was compromised. The animals that had received hESC-OPCs showed significantly greater improvement in forelimb stride length and range of motion compared to untreated controls.
“We are excited by Dr. Keirstead’s study in the cervical injury model,” said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. “These preclinical studies demonstrate that transplantation of hESC-derived OPCs resulted in sparing of spinal cord tissue in the cervical lesion site. This sparing starts very soon after injection and importantly, results in the preservation of motor neurons which is correlated to recovery of forelimb movement. Our own IND-enabling safety and efficacy studies with GRNOPC1 in a cervical injury model are ongoing and will be submitted to the FDA upon completion.”
Disruptions in liver and brain clocks contribute to unhealthy eating patterns