Objective: This first-in-human study aims to evaluate the safety of hOMNSC300 following intrathecal administration in patients with moderate to advanced MSA.

Background: Stem cell therapy is being explored as a potential disease-modifying treatment for Multiple System Atrophy (MSA). Human oral mucosa-derived neural crest stem cells (hOMNSC300) are an allogeneic, off-the-shelf biologic, derived from the lamina propria of the oral mucosa. Preclinical studies indicate their safety and efficacy.

Method: An open-label, single-center Phase 1 safety study with escalating doses was conducted in 10 subjects with moderate (n=4; UMSARS II range 13-19) and advanced (n=6; UMSARS II range 26-41) MSA-C (n=8) or MSA-P (n=2). Subjects received a single intrathecal dose of hOMNSC300 (2 subjects: 37.5 million cells; 8 subjects: 75 million cells) with 18 months of follow-up. Primary safety endpoints included treatment-related serious adverse events (SAEs) and adverse events (AEs). Exploratory endpoints involved changes from baseline in motor and non-motor clinical characteristics and MRI volumetric measurements.

Results: The study is ongoing. Safety data from 3-18 months post-administration showed no treatment-related SAEs. Four deaths occurred in the advanced MSA group, attributed to aspiration and sepsis, unrelated to the investigational product. A total of 46 resolved AEs were reported, 16 possibly or likely related, including asymptomatic pleocytosis (n=7), lumbar root enhancement (n=2), back/leg pain (n=2), and post-lumbar puncture symptoms.

Exploratory Findings: In the moderate group, UMSARS II scores changed by 1.5 points (range 0-4) at 3 months and 1.66 points (range -1 to 4) at 6 months. In the advanced group, changes were 2.66 points (range -2 to 9) at 3 months and 8 points (range 2 to 18) at 6 months. The 6-month average change in the moderate group (1.66) was lower than the natural history data (5.3). MRI volumetry showed mild cerebellar white matter loss (10-13%) in 2 of 6 subjects at 6 months, with no significant changes in cerebrum or deep nuclei volumes.

Conclusion: Conclusions: Safety data indicates that intrathecal administration of hOMNSC300 is safe. UMSARS and MRI volumetry suggest that hOMNSC300 may have potential as a disease-modifying therapy in moderate-stage MSA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intrathecal-administration-of-human-oral-mucosa-neural-crest-stem-cells-in-moderate-advanced-multiple-system-atrophy-report-on-ongoing-phase-1-study/