Is HLA matching relevant for treating Spinal Cord Injury with intrathecal administration of expanded Wharton's Jelly Mesenchymal Stromal Cells?

Abstract

Background & Aim Background Spinal cord injury (SCI) is a devastating pathology with no effective treatment. There are several treatment approaches under investigation and Mesenchymal Stromal Cells (MSC) are within one of the preferred cells under investigation. Autologous treatment requires previous patient's surgery resulting in long and expensive procedure but allogeneic cryopreserved Wharton jelly (WJ) MSC is a ready to use product with increasing interest. Methods, Results & Conclusion Methods Phase I/IIa, randomized, two-arm, double-blind, placebo-controlled trial in 10 patients affected with chronic traumatic SCI (T2-T11, ASIA A) (NCT03003364). Primary and secondary objectives were safety and efficacy, respectively. Patients were randomized to WJ-MSC/Placebo (PLC) or PLC/WJ-MSC and received the 1st infusion. At 6m all patients, except 1 (voluntarily withdrawn), received the 2nd infusion. At 12m, patients were asked to give consent to receive an additional infusion of WJ-MSC with a follow-up to month 24. Medication contained 10 × 106 WJ-MSC in a 4±1ml prefilled blinded syringe. Allelic profile was obtained from a sample of WJ-MSC of the donated umbilical cord units (UCu) and from all patients, but the compatibility was not a requirement to select the donor. Revision of results were made to identify whether the HLA compatibility resulted in a better response to treatment. The study was conducted between Nov 2017 and Jul 2019. Results 9 patients received 2 WJ-MSC and 1 PLC. Patient (P)#6 withdraw voluntarily after the 3rd infusion. 2 UCu were used to produce all dosages. Allelic profiles (UCu and patients) are detailed in table 1 and 2. No relevant safety issues were detected during the trial. Anti-HLA Ab and chimerism resulted all negative after the 1st active infusion, but patient #1 developed Abs to both UCu after the 2nd active infusion. No changes were detected in the ASIA classification or for the lower extremity motor subscores. For the rest of ISNCSCI parameters (table 3), P#1 and P#4 had the best response, while P#10 and P#2 had the worst one. Based on HLA compatibility one could expect a better response for P#2 and P#6, but this was not the case. Conclusions A better response has not been detected in patients with a greater degree of HLA compatibility with the treatment, so the patient's compatibility seems independent of the response to the treatment. There is the need to deeper investigate other or concomitant parameters that could explain the difference in the response to treatment.