Oligodendrocyte progenitor cells (LCTOPC1; Lineage Cell Therapeutics) can be safely administered to participants in the subacute period after cervical spinal cord injury (SCI), according to the results of a phase 1/2 a dose-escalation study which were recently published in the Journal of Neurosurgery: Spine by Richard Fessler (Rush University Medical Center, Chicago, USA) et al.
The injection procedure, low-dose temporary immunosuppression regimen, and LCTOPC1 were found to be well tolerated. The researchers add that the safety and neurological function data “support further investigation to determine the efficacy of LCTOPC1 in the treatment of SCI”.
The primary aim of the study was to evaluate the safety of three escalating doses of LCTOPC1 (previously known as GRNOPC1 and AST-OPC1) administered at a single time point between 21 and 42 days post-injury to participants with subacute cervical SCIs. The secondary objective was to evaluate changes in neurological function following administration of LCTOPC1.
The study was designed as an open-label, dose-escalation, multicentre clinical trial. A total of 25 participants with C4–7 American Spinal Injury Association Impairment Scale grade A or B injuries received a single dose of either 2×106, 1×107, or 2×107 LCTOPC1 delivered via intraparenchymal injection into the spinal cord at the site of injury using a custom-designed syringe positioning device. Low-dose tacrolimus was administered until day 60.
Outcome measures included adverse event (AE) monitoring and neurological function as measured by the International Standards for Neurological Classification of Spinal Cord Injury.
All 25 participants experienced at least one AE, with a total of 534 AEs (32 study-related vs. 502 study-unrelated anticipated complications of SCI) reported at the completion of one-year follow-up.
There were 29 serious AEs reported. Two grade three serious AEs (cerebrospinal fluid [CSF] leak in one participant and a bacterial infection in another) were considered related to the injection procedure and to immunosuppression with tacrolimus, respectively. The CSF leakage resolved with sequelae, including self-limited altered mental status, and the infection resolved with antibiotic therapy.
For all participants, MRI scans demonstrated no evidence of an enlarging mass, spinal cord damage related to the injection procedure, inflammatory lesions in the spinal cord, or masses in the ventricular system.
At one-year follow-up, 21/22 (96%) of the intention-to-treat group recovered one or more levels of neurological function on at least one side of their body, and 7/22 (32%) recovered two or more levels of neurological function on at least one side of their body.
Speaking to Spinal News International, Fessler said: “This human trial yielded exciting results not only demonstrating the safety of this treatment, but also pointed toward significant clinical improvement in these severely injured patients. The results will inform the design not only of future human trials but also the direction of basic research to determine how to maximise future clinical benefit.”