ABSTRACT

Background

Advanced cell therapeutics are emerging as potentially effective treatments for chronic neurological diseases, including secondary progressive multiple sclerosis (SPMS). Here we report the results of a phase I trial in which good manufacturing practice-grade foetal allogeneic human neural stem cells (hNSCs) were implanted via intracerebroventricular (ICV) injection in 15 individuals with active and non-active SPMS.

Methods

This is a phase I, open-label, multicentre, dose-escalation, international study. The primary objective was to assess the feasibility, safety, and tolerability of ICV injections of allogeneic hNSCs in patients affected by SPMS over a study follow up of 12 months. We also evaluated the number and type of adverse events (AEs) leading to a maximum tolerated dose, the general health status, and mortality. The secondary objectives were the therapeutic benefit of allogeneic hNSCs using assessment scales, magnetic resonance imaging (MRI), and laboratory and neurophysiologic parameters.

Findings

Fifteen unrelated SPMS patients were enrolled and treated between 2018 and 2020. The participants had a median age of 49.8 years. Their mean extended disability status scale (EDSS) at enrolment was 7.6, the mean disease duration was 22 years, and mean time from diagnosis to progression was 10.1 years. Neither treatment-related deaths nor serious AEs were reported during the study (1 year follow up after treatment). All the other AEs were classified as non-serious and were associated to non-study concomitant therapy or other medical conditions not connected to the experimental treatment. During the study, none of the participants worsened in the progression of their SPMS as shown by the evaluation scales implemented to assess their progress. Laboratory and neurophysiologic parameters showed no clinically significant variations. MRI follow-up showed non-clinically significant type 1, 2, and 3 changes.

Interpretation

The intracerebroventricular injection of foetal allogeneic hNSCs in people with SPMS is feasible, tolerated and safe. Study participants displayed a substantial clinical stability during the 12-month follow-up. The absence of relevant adverse reactions (Ars) arising from the transplantation of hNSCs indicates a short-term neutral balance between benefits and risks and suggests a concrete, though perspective therapeutic possibility for SPMS patients. Further studies are needed to confirm and extend the findings herein and evaluate the actual therapeutic potential of advanced cell therapeutics for a condition where the lack of effective disease modifying therapies is a major unmet clinical need.