Abstract Details

Title Results from a Phase 2 Clinical Trial of Repeated Intrathecal Autologous Adipose-derived MSCs in ALS

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S5 - ALS and CMT: New Therapeutic Approaches (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

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.

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.

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

Our multi-site Phase 2 clinical trial of MSC therapy in ALS has completed enrollment, and we will report top-line results at the meeting. The clinical trial endpoint data and biomarker analyses will help inform future studies of MSCs in ALS.

Authors/Disclosures
Nathan P. Staff, MD, PhD, FAAN (Mayo Clinic) PRESENTER	Dr. Staff has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stem Cell Research & Therapy. Dr. Staff has received research support from National Institutes of Health.
Bjorn E. Oskarsson, MD, FAAN (Mayo Clinic)	Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. The institution of Dr. Oskarsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AnnJi. The institution of Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Oskarsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Tsumura. The institution of Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MediciNova. The institution of Dr. Oskarsson has received research support from Biogen. The institution of Dr. Oskarsson has received research support from Medicinova. The institution of Dr. Oskarsson has received research support from Cytokinetics. The institution of Dr. Oskarsson has received research support from Calico. The institution of Dr. Oskarsson has received research support from Mitsubishi. The institution of Dr. Oskarsson has received research support from Tsumura. The institution of Dr. Oskarsson has received research support from Sanofi. The institution of Dr. Oskarsson has received research support from AZTherapeutics. The institution of Dr. Oskarsson has received research support from Orion. The institution of Dr. Oskarsson has received research support from Esaii.
Iryna Muzyka, MD (Mayo Clinic)	Dr. Muzyka has nothing to disclose.
Nicolas Madigan, MD	Dr. Madigan has nothing to disclose.
Carly Mester	No disclosure on file
Daniel Figdore	No disclosure on file
Michelle Turner (Mayo Clinic Rochester)	No disclosure on file
Lisa Thuro (Mayo Clinic)	No disclosure on file
Thomas Osgood	No disclosure on file
Pranathi Madde (Mayo clinic)	No disclosure on file
Michael Deeds (Mayo Clinic)	No disclosure on file
Timothy Wiltshire	No disclosure on file
Alicia Algeciras-Schimnich	No disclosure on file
Jayawant N. Mandrekar, PhD	Dr. Mandrekar has nothing to disclose.
Allan Dietz	No disclosure on file
Anthony J. Windebank, MD, FAAN (Mayo Clinic)	Dr. Windebank has nothing to disclose.