Allogeneic mesenchymal stem cell therapy with laromestrocel in mild Alzheimer’s disease: a randomized controlled phase 2a trial
Bibliographic record
Abstract
Alzheimer's disease (AD) is characterized by progressive cognitive decline, severe brain atrophy and neuroinflammation. We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 2a clinical trial that tested the safety and efficacy of laromestrocel, a bone-marrow-derived, allogeneic mesenchymal stem-cell therapy, in slowing AD clinical progression, atrophy and neuroinflammation. Participants across ten centers in the United States were randomly assigned 1:1:1:1 to four infusion groups: group 1 (placebo; four monthly infusions, n = 12); group 2 (25 million cells, one infusion followed by three monthly infusions of placebo, n = 13); group 3 (25 million cells; four monthly doses, n = 13); and group 4 (100 million cells; four monthly doses, n = 11). The study met its primary end point of safety; the rate of treatment-emergent serious adverse events within 4 weeks of any infusion was similar in all four groups: group 1, 0% (95% CI 0-26.5%); group 2, 7.7% (95% CI 0.2-36%); group 3, 7.7% (95% CI 0.2-36%) and group 4, 9.1% (95% CI 0.2-41.3%). Additionally, there were no reported infusion-related reactions, hypersensitivities or amyloid-related imaging abnormalities. Laromestrocel improved clinical assessments at 39 weeks compared to placebo, as measured by a composite AD score (secondary end point was met: group 2 versus placebo change: 0.38; 95% CI -0.06-0.82), Montreal cognitive assessment and the Alzheimer's Disease Cooperative Study Activities of Daily Living. At 39 weeks, Laromestrocel slowed the decline of whole brain volume compared to placebo (n = 10) by 48.4% for all treatment groups combined (groups 2-4: P = 0.005; n = 32) and left hippocampal volume by 61.9% (groups 2-4, P = 0.021; n = 32), and reduced neuroinflammation as measured by diffusion tensor imaging. The change in bilateral hippocampal atrophy correlated with the change in mini-mental state exam scores (R = 0.41, P = 0.0075) in all study patients (N = 42). Collectively these results support safety of single and multiple doses of laromestrocel treatment for mild AD and provide indications of efficacy in combating decline of brain volume and potentially cognitive function. Larger-scale clinical trials of laromestrocel in AD are warranted. ClinicalTrials.gov registration: NCT05233774 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".