Objective:

In this Phase 2 open label clinical trial, we aim to evaluate the safety and efficacy of repeated intrathecal autologous adipose-derived mesenchymal stromal cells (MSCs) in people living with ALS.

Background:

Mesenchymal stromal cells (MSCs) are being developed as a treatment for amyotrophic lateral sclerosis (ALS), and are hypothesized to exert their effects via growth factor secretion and immunomodulation. 

Design/Methods:

During a 3-month lead-in period subjects undergo a fat biopsy for isolation and expansion of MSCs. Participants receive 4 treatments (10-100 x 10^6 MSCs), spaced 3 months apart. The primary analysis for efficacy is ALSFRS-R progression in the study group compared with a cohort of subjects from the PRO-ACT ALS clinical trial database that will be matched for age, gender, and riluzole use.  A Secondary responder analysis will be reported. Serial blood, cerebrospinal fluid, MRI spine imaging, and clinical phenotyping are collected for each participant.

Results:

Enrollment was completed in July 2023, and last participant visit will be completed in January 2024.  75 subjects have been enrolled, and 58 people with ALS have been fully accrued and received at least one treatment; at time of abstract presentation all treatments will be completed. Mean age of subjects is 56.3 with a male predominance. 14 have familial ALS (9 genetically confirmed). The mean (range) ALSFRS-R at enrollment is 37 (19-47). Mean (range) baseline plasma neurofilament light chain level is 83.7 pg/mL (16.3-373.8). Intrathecal MSC therapy is generally well-tolerated with the most common adverse event being temporary back and leg pain.  Full adverse event data and efficacy results will be reported.

Conclusions: