One-year results from a phase I clinical trial (NCT03282760) demonstrated the feasibility, safety, and tolerability of intracerebroventricular (ICV) human neural stem/progenitor cell (hNSC) transplantation in patients with secondary progressive multiple sclerosis (SPMS). Results were published in a recent issue of Cell Stem Cell.

The open-label, first-in-human, dose-escalation trial was conducted at 3 sites in Italy and Switzerland and included 15 participants with SPMS (mean time from diagnosis to secondary progression was 10 years) aged 39 to 57 years, with an Expanded Disability Status Scale (EDSS) score of 7 to 8, and an absence of therapeutic alternatives as judged by a treating neurologist. Treatment was initiated after a 3 month period in which clinical and radiologic baseline features were established for each participant. Participants were randomly enrolled into 1 of 4 treatment dosage cohorts according to a standard dose-escalation method that followed a modified Fibonacci sequence (100%, 60%, and 50% dose increments) and received a single ICV injection of the hNSC 03/14b line (5, 10, 16, or 24 x 10⁶ cells) delivered via a catheter. Ventricular cannulation was performed using the Stealth Station AxiEM Electromagnetic Tracking System (Medtronic Navigation, Louisville, CO).

Researchers categorized new-onset parenchymal brain volume changes (PBVC), and Spearman’s analysis demonstrated an inverse correlation between the dose of injected hNSCs and PBVC (Spearman’s Rho = 0.7, P=.0205). At 24 hours post-surgery, participants underwent a CT scan for assessment of any surgery-related complications. The health status and disease progression of each participant were monitored with monthly visits for a total of 12 months and indicated the following:

• No deaths or serious adverse events
• No changes in functional disability and clinical progression of the disease
• No influence of treatment on MRI inflammatory activity (annualized rate of new or enlarging T2-visible lesions and lesions with contrast enhancement)

This is the first and largest clinical trial to use hNSCs in people with SPMS. Key limitations to this study include the lack of a placebo control group, the relatively short follow-up period, and the fact that the mechanism(s) of action of the hNSC 03/14b drug remains undetermined, limiting some of the conclusions regarding drug efficacy.