Laromestrocel preserves brain volume and cognitive function in Alzheimers disease by inhibiting neuroinflammation

Neuroinflammation is a principal driver of brain atrophy and cognitive decline in Alzheimers disease (AD). Here we show that laromestrocel, a mesenchymal stem cell therapy, inhibits progressive brain inflammation in subjects (n=49) with mild AD, with the strongest effect seen in core AD brain regions: the left hippocampus (25 million cells (M)x4 monthly dose group; p<0.001, N=11, and 100Mx4 group; p<0.001; N=10), the left temporal cortex (25Mx4 group; p=0.007; N=11) and left parietal cortex (25Mx4, week 26; p=0.042; N=10), and the medulla (25Mx4 group and 100Mx4; p=0.007; N=11 and N=10) after 39 weeks compared with placebo (N=9). Reduced neuroinflammation correlated with reduced brain atrophy (hippocampus: R=-0.326; p=0.040; N=40) and improvements in clinical scores, particularly cognitive function (hippocampus x MoCA: R=-0.401; p=0.011; N=40). Treated subjects also exhibited reduced neurogranin (25Mx4 group; p=0.023; N=11) in blood plasma, consistent with reduced synaptic loss. Finally, blood biomarker analysis supported a convergent multimodal mechanism of action implicating peripheral immune engagement. Together these results show that long-lasting anti-neuroinflammatory effects of laromestrocel mitigate AD brain inflammation and are associated with markedly reduced brain tissue destruction and improved clinical function.