Preclinical and Phase I Development of Oligodendrocyte Progenitor Cells Derived From Human Embryonic Stem Cells for the Treatment of Spinal Cord Injury
Multiple preclinical studies were performed over a period of several years to evaluate the efficacy and safety of GRNOPC1, a cryopreserved population of differentiated cells containing oligodendrocyte progenitors derived from human embryonic stem cells. Preclinical efficacy of both fresh and cryopreserved GRNOPC1 was evaluated with respect to locomotor function in rats that had received a contusion injury to the spinal cord at the T9-T10 thoracic level. Preclinical safety of GRNOPC1 was assessed in several extensive studies involving rats with thoracic contusion injuries and mice with intact spinal cords, and animals were followed up to 12 months post-injection.
In preclinical efficacy studies, GRNOPC1 improved hindlimb locomotor activity in rats when implanted 7 days after injury near the epicenter of the lesion. Fascicles of myelinated neural fibers were observed traversing the injury epicenter after GRNOPC1 injection, but not in animals injected with vehicle alone. The safety studies showed no evidence of teratoma formation 12 months after injection of clinical grade GRNOPC1, and demonstrated the absence of significant migration of the injected cells outside the spinal cord, allodynia induction, systematic toxicity or increased mortality in animals receiving GRNOPC1. The results from the 24 preclinical studies where over 850 animals were injected with GRNOPC1 were submitted as part of an Investigational New Drug (IND) application to the FDA. A phase 1 clinical trial was recently initiated to assess the safety of GRNOPC1 in patients with subacute, complete (ASIA A), thoracic injuries whose last fully preserved neurological level is T3 to T10.