Laromestrocel — Allogeneic Bone Marrow MSC for Mild Alzheimer's Disease, Phase 2a
No ARIA (amyloid-related imaging abnormalities) observed. Signals of attenuated cognitive decline and brain atrophy at 9 months.
| Trial ID | NCT05233774 ↗ |
|---|---|
| Sponsor | Longeveron · USA |
| Cell Source | 골수 중간엽줄기세포 (BM-MSC) · allogeneic |
| Indication | 알츠하이머병 · Alzheimer's Disease |
| Phase | PHASE 2A |
| Status | COMPLETED |
| Delivery Route | intravenous infusion (IV) |
| Enrollment | 49 |
| Publication | Nature Medicine 2025 · DOI ↗ |
Trial Design
A randomised, double-blind, placebo-controlled, parallel-group study conducted across 10 centres in the United States. Forty-nine patients with mild Alzheimer’s disease were randomised 1:1:1:1 across four treatment arms.
- Arm 1 (n=12): placebo — four monthly infusions
- Arm 2 (n=13): 25 million cells × 1 infusion + placebo × 3 infusions
- Arm 3 (n=13): 25 million cells × 4 monthly infusions
- Arm 4 (n=11): 100 million cells × 4 monthly infusions
Key Results
The primary endpoint (safety) was met. The incidence of treatment-related serious adverse events within 4 weeks of infusion was comparable across all arms (0–9.1%), and no infusion-related reactions, hypersensitivity responses, or amyloid-related imaging abnormalities (ARIA) were reported.
Exploratory efficacy endpoints showed improvement in clinical assessments at week 39 relative to placebo, with signals suggesting a reduction in cognitive decline and brain atrophy at the 9-month timepoint.
Clinical Significance
The central reason this outcome has attracted attention is the absence of ARIA. Currently approved anti-amyloid antibody therapies (lecanemab and donanemab) are constrained in their eligible patient population by the risk of ARIA. The results open the possibility of MSCs serving as a complementary or alternative option for patients at elevated ARIA risk — such as ApoE4 homozygotes and those on anticoagulation therapy — who cannot be safely treated with antibody-based agents.
Equally important is the observation that cognitive and brain-atrophy signals were detected following intravenous infusion alone, despite the conventional understanding that cells do not cross the BBB. This strongly suggests that the operative mechanism is not direct differentiation of MSCs but rather remote neuroprotective and anti-inflammatory effects mediated via the secretome or exosomes.
Korean Adoption Perspective
The MFDS classifies allogeneic MSCs as advanced biopharmaceuticals under the Act on the Safety and Support of Advanced Regenerative Medicine and Advanced Biopharmaceuticals. The intravenous delivery route lowers the barrier to adoption in healthcare settings. However, the cost structure of a multi-dose protocol (once monthly × 4 infusions) and the feasibility of health insurance reimbursement are the critical variables that will determine whether clinical adoption is realised.
Follow-on Trials
As of the end of 2025, advancement to Phase 3 had not been announced. Nevertheless, given that safety and efficacy signals were both established, progression to a confirmatory trial would be the natural and expected next step.