OLIGODENDROCYTE PROGENITOR CELLS (GRNOPC1)

Geron's hESC-Derived Oligodendrocyte Progenitor Cells - GRNOPC1
Geron's first product manufactured from hESCs to enter clinical testing is GRNOPC1. GRNOPC1 is a population of living cells containing precursors to oligodendrocytes, otherwise known as oligodendrocyte progenitor cells (OPC). Oligodendrocytes are naturally occurring cells in the nervous system that have several functions. Oligodendrocytes produce myelin (insulating layers of cell membrane) that wraps around the axons of neurons to enable them to conduct electrical impulses. Myelin enables efficient conduction of nerve impulses in the same manner as insulation prevents short circuits in an electrical wire. Without myelin, many of the nerves in the brain and spinal cord cannot function properly. Oligodendrocytes also produce neurotrophic factors (biologicals that enhance neuronal survival and function) to support the maintenance of nerve cells. Oligodendrocytes are lost in spinal cord injury, resulting in myelin and neuronal loss that cause paralysis in many patients with spinal cord injuries.

In preclinical studies, GRNOPC1, when injected into the injury site of spinal cord-injured animals, migrate throughout the lesion site and mature into functional oligodendrocytes that remyelinate axons and produce neurotrophic factors (Stem Cells and Development, Vol. 15, 2006), resulting in improved locomotion in the treated animals.

The ultimate goal for the use of GRNOPC1 in man is to achieve spinal cord repair by injecting these cells directly into the spinal cord lesion.

The Pathology of Acute Spinal Cord Injury
Most human spinal cord injuries are due to contusions (bruises), rather than to a severing of the spinal cord. Most automobile, sports or industrial accidents cause a displacement or crush of the vertebral bodies in the cervical or thoracic spine that results in a contusion within the spinal cord, damaging the delicate nerve fibers at the site of the fracture. Spinal cord injuries cause severe inflammation within the spinal cord at the site of the fracture that is particularly toxic to the oligodendrocytes in the spinal cord.

GRNOPC1 Restores Locomotion in Rodent Models of Spinal Cord Injury
Geron scientists, in collaboration with Dr. Hans Keirstead's laboratory at the University of California, Irvine, developed a method to produce oligodendrocyte progenitor cells from hESCs. These cells were tested in a validated rodent model of acute spinal cord injury. Under anesthesia, animals were given a spinal cord contusion injury, mimicking what occurs in humans who suffer traumatic injury to the spinal cord. The lesions resulted in loss of truncal muscle function, bladder control and hind limb function. The injured animals received either no treatment, control cells or media, or one injection of GRNOPC1 within seven days after injury. Animals were then carefully followed and observed for locomotor recovery after the injury.

Injured animals treated with GRNOPC1 displayed significant improvement in a variety of functional parameters compared to control groups. GRNOPC1-treated animals had improved hind limb locomotor control. Paw placement, stride length and paw rotation all significantly improved compared to controls. When the GRNOPC1-treated animals were examined histologically, increased remyelination of axons in the injury site was observed compared to that in the control animals. An increased number of axons were also observed in the vicinity of the injection within the injury. These animal results were published in the Journal of Neuroscience, Vol. 25, May 2005. In additional studies, the lesion site of animals nine months after injury and injection of GRNOPC1 was observed to be essentially filled with GRNOPC1 and mye­linated rat axons crossing the lesion. These animal observations serve as the rationale for the use of GRNOPC1 in treating spinal cord injuries in man.