Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury

Author:

McKenna Stephen L.12,Ehsanian Reza3,Liu Charles Y.45,Steinberg Gary K.2,Jones Linda6,Lebkowski Jane S.78,Wirth Edward79,Fessler Richard G.10

Affiliation:

1. Department of Physical Medicine and Rehabilitation, Santa Clara Valley Medical Center, San Jose, California;

2. Department of Neurosurgery, Stanford University School of Medicine, Stanford, California;

3. Division of Physical Medicine and Rehabilitation, Department of Orthopedics & Rehabilitation, University of New Mexico School of Medicine, Albuquerque, New Mexico;

4. USC Neurorestoration Center, Los Angeles, California;

5. Rancho Los Amigos National Rehabilitation Center, Downey, California;

6. Thomas Jefferson University, Philadelphia, Pennsylvania;

7. Asterias Biotherapeutics, a wholly owned subsidiary of Lineage Cell Therapeutics, Carlsbad, California;

8. Regenerative Patch Technologies, LLC, Menlo Park, California;

9. Aspen Neuroscience, San Diego, California; and

10. Department of Neurosurgery, Rush University Medical Center, Chicago, Illinois

Abstract

OBJECTIVE The purpose of this study was to evaluate the safety of oligodendrocyte progenitor cells (LCTOPC1) derived from human pluripotent stem cells administered between 7 and 14 days postinjury to patients with T3 to T11 neurologically complete spinal cord injury (SCI). The rationale for this first-in-human trial was based on evidence that administration of LCTOPC1 supports survival and potential repair of key cellular components and architecture at the SCI site. METHODS This study was a multisite, open-label, single-arm interventional clinical trial. Participants (n = 5) received a single intraparenchymal injection of 2 × 106 LCTOPC1 caudal to the epicenter of injury using a syringe positioning device. Immunosuppression with tacrolimus was administered for a total of 60 days. Participants were followed with annual in-person examinations and MRI for 5 years at the time of this report and will be followed with annual telephone questionnaires for 6 to 15 years postinjection. The primary endpoint was safety, as measured by the frequency and severity of adverse events related to the LCTOPC1 injection, the injection procedure, and/or the concomitant immunosuppression administered. The secondary endpoint was neurological function as measured by sensory scores and lower-extremity motor scores as measured by the International Standards for Neurological Classification of Spinal Cord Injury examinations. RESULTS No unanticipated serious adverse events related to LCTOPC1 have been reported with 98% follow-up of participants (49 of 50 annual visits) through the first 10 years of the clinical trial. There was no evidence of neurological decline, enlarging masses, further spinal cord damage, or syrinx formation. MRI results during the long-term follow-up period in patients administered LCTOPC1 cells showed that 80% of patients demonstrated T2 signal changes consistent with the formation of a tissue matrix at the injury site. CONCLUSIONS This study provides crucial first-in-human safety data supporting the pursuit of future human embryonic stem cell–derived therapies. While we cannot exclude the possibility of future adverse events, the experience in this trial provides evidence that this cell type can be well tolerated by patients, with an event-free period of up to 10 years. Based on the safety profile of LCTOPC1 obtained in this study, a cervical dose escalation trial was initiated (NCT02302157).

Publisher

Journal of Neurosurgery Publishing Group (JNSPG)

Subject

General Medicine

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