MRI Analysis Shows Stem Cell Therapy Laromestrocel Reduced Neuroinflammation in Mild Alzheimer Disease

A new MRI analysis from the phase 2a CLEAR MIND trial (NCT05233774) indicated that laromestrocel (Longeveron), an investigational mesenchymal stem cell therapy, was associated with reduced brain neuroinflammation compared with placebo across multiple brain regions in patients with mild Alzheimer disease (AD), particularly the hippocampus and temporal lobe.¹ These findings suggest a sustained anti-inflammatory effect of laromestrocel, reinforcing its proposed mechanism of action in mild AD and supporting continued clinical development of the therapy.

In the study, presented at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference, held December 1-4, 2025, in San Diego, California, investigators evaluated the effects of laromestrocel treatment on neuroinflammation in patients enrolled in CLEAR MIND using diffusion tensor imaging and free water analysis. Findings revealed that patients treated with laromestrocel demonstrated a durable reduction in free water fraction compared with placebo (N = 11) at 39 weeks for several brain regions.

“Laromestrocel, a stem cell therapy that has multiple potential mechanisms of action to address inflammatory responses in the brain, offers the potential to address the underlying pathology of Alzheimer’s disease,” Joshua Hare, MD, co-founder, chief science officer, and executive chairman at Longeveron, said in a statement.¹ “This data expands on the positive clinical information from the Phase 2a CLEAR MIND clinical trial that showed laromestrocel improved cognitive function, quality of life, and brain volume in the treatment of mild Alzheimer’s disease. We are very encouraged by the safety profile and efficacy evidence that support the differentiated therapeutic potential of laromestrocel in Alzheimer’s disease.”

The CLEAR MIND trial comprised of 50 patients aged between 60 and 85 years with a diagnosis of mild AD in accordance with National Institutes of Health-Alzheimer’s Association criteria, a Mini-Mental State Exam (MMSE) score of 18-24, and a brain MRI and PET scan consistent with AD. In the trial, patients were randomly assigned 1:1:1:1 to either laromestrocel at a dose of 25 x 106 cells (25M) on day 0, followed by placebo infusions at weeks 4, 8 and 12; laromestrocel at a dose of 25M administered on day 0, week 4, week 8, and week 12 for a total of 4 doses; and at a dose of 100 x 106 cells (100M) administered on day 0, week 4, week 8, and week 12, for a total of 4 doses.

In the presented analysis, researchers observed reductions in the hippocampus (Group 4, P = .004, N = 8; Group 3, P = .037, N = 8), which showed a dose response, as well as the temporal cortex (Group 3, P = .032, N = 8), occipital cortex (Group 3, P = .003, N = 8), and parietal cortex (Group 3, P = .038, N = 8). Authors noted that these findings coincided with previously reported clinical outcomes and reduced brain atrophy. Of the 14 brain regions, all but frontal cortex showed pooled treatment group responses (Groups 2, 3, and 4 combined) indicating a reduction in free water by 39 weeks.

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Topline results of the trial showed that the investigational stem cell therapy laromestrocel met its primary end point of safety, with slowing of disease worsening in patients with mild AD. At the end of the 39-week treatment period, investigators reported no new safety concerns, in addition to no cases of amyloid-related imaging abnormalities, no clinically asymptomatic microhemorrhages on MRI, and no notable changes in laboratory evaluations and electrocardiogram.²

In terms of efficacy, statistically significant improvements in the Composite Alzheimer’s Disease Score (CADS) were observed after 39 weeks in the laromestrocel 25 x 106 cells (25M) x 1 dose (P = .091) vs placebo and for the pooled laromestrocel groups (25M x 1 dose, 25M x 4 doses, 100 x 106 cells [100M] x 4 doses; P = .099). CAD combines the Alzheimer’s Disease Assessment Scale- Cognitive subscale 13, Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Clinical Dementia Rating-Sum of Boxes, and left hippocampal volume. For the laromestrocel 25M x 1 dose group, treated patients saw a statistically significant slowing of disease progression in left hippocampal volume (P = .015) relative to placebo.

Additional clinical data and imaging biomarker results, announced in 2023, further highlighted laromestrocel’s impact on AD. All told, laromestrocel (25M x 1 dose, P = .009) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, P = 0.015) demonstrated statistically significant improvements in the Montreal Cognitive Assessment (MOCA), relative to placebo. In addition, investigators observed a dose-dependent response improvement in MMSE for laromestrocel -treated patients (mean increase at highest dose: 3.0 [± 3.6]; P = .028). Furthermore, quality of life, measured by the Alzheimer’s Disease Related Quality of Life scale, revealed higher level of improvement in patients on active therapy (100M x 4 doses).³

Supplementary data from CLEAR MIND also showed that laromestrocel (100M x 4 doses) reduced whole brain volume loss by 49% (P = .034). Additionally, laromestrocel (25M x 1 dose, P = .015) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, P = .038) demonstrated statistically significant reductions in left hippocampal volume loss at Week 39 relative to placebo (25M x 1 dose degree of reduction: 84%). Lastly, brain volume preservation in the laromestrocel (100M x 4 dose) dose group was accompanied by 20% and 33% reduction in left and right ventricular enlargement, respectively, at week 39 compared with placebo.

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REFERENCES
1. Longeveron New MRI Biomarker Data Linking Neuroinflammation to Clinical Outcomes in Patients with Mild Alzheimer’s Disease Presented at the Clinical Trials on Alzheimer’s Disease Conference (CTAD 2025). News release. December 1, 2025. Accessed December 1, 2025. https://investors.longeveron.com/news/News/news-details/2025/Longeveron-New-MRI-Biomarker-Data-Linking-Neuroinflammation-to-Clinical-Outcomes-in-Patients-with-Mild-Alzheimers-Disease-Presented-at-the-Clinical-Trials-on-Alzheimers-Disease-Conference-CTAD-2025/default.aspx
2. Longeveron announces positive top-line results for Lomecel-B in its CLEAR MIND phase 2a clinical trial in the treatment of mild Alzheimer’s disease. News release. Longeveron. October 5, 2023. Accessed December 1, 2025. https://investors.longeveron.com/news/News/news-details/2023/Longeveron-Announces-Positive-Top-Line-Results-for-Lomecel-B-in-its-CLEAR-MIND-Phase-2a-Clinical-Trial-in-the-Treatment-of-Mild-Alzheimers-Disease/default.aspx
3. Longeveron announces additional positive clinical data and imaging biomarker results from the CLEAR MIND phase 2a trial of Lomecel-B in the treatment of mild Alzheimer disease. December 20, 2023. Accessed December 1, 2025. https://investors.longeveron.com/news/News/news-details/2023/Longeveron-Announces-Additional-Positive-Clinical-Data-and-Imaging-Biomarker-Results-from-the-CLEAR-MIND-Phase-2a-Trial-of-Lomecel-Bin-the-Treatment-of-Mild-Alzheimers-Disease/default.aspx