Stem Cell Therapy Reduced Brain Atrophy in People with Mild Alzheimer Disease

The intravenous (IV) treatment of people with mild Alzheimer disease (AD) using Lomecel-B (laromestrocel; Longeveron, Miami, FL), a bone-marrow–derived allogeneic mesenchymal stem cell (MSC), was associated with reduced atrophy of the whole brain and hippocampus compared with placebo. These results of the phase 2 CLEARMIND clinical trial (NCT053233774), published in Nature Medicine, demonstrate the potential of a new mechanism for treating AD beyond amyloid targeting.

CLEARMIND was a randomized, double-blind, placebo-controlled phase 2a clinical trial including a total of 49 participants aged 60 to 85 years with a clinical diagnosis of mild AD who were randomized 1:1:1:1 to receive monthly infusions with either placebo (n=12) or Lomecel-B at 3 dosing regimens, including:

• A single dose of 25 million cells at day 0 followed by 3 infusions of placebo administered over 3 months (n=13)
• 4 infusions of 25 million cells administered over 4 months (n=13)
• 4 infusions of 100 million cells administered over 4 months (n=12)

Key results at 39 weeks include the following:

• Participants from all Lomecel-B–treated groups combined (groups 2-4; n=32) showed 48% slower whole brain volume decline (P=.005) and 59% slower bilateral hippocampal volume decline vs placebo (P=.013)
• Participants from all Lomecel-B–treated groups combined (n=32; P=.015) and those in group 2 (n=11; P=.009) showed significantly improved Montreal Cognitive Assessment (MoCA) compared with placebo.
• Participants in treatment group 4 (n=10) showed significantly improved scores on the Activities of Daily Living (ADCS-ADL) scale compared with placebo (P=.040).

Lomecel-B also met the study’s primary endpoint of safety, with similar rates of treatment-emergent serious adverse events across all 4 treatment groups and no infusion-related reactions, hypersensitivities, or amyloid-related imaging abnormalities (ARIA). The study was conducted with support from Longeveron.