Laromestrocel preserves brain volume and cognitive function in Alzheimer’s disease by inhibiting neuroinflammation

Product:

CNS Disease Panel 120

Topic:

Neurology

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Abstract

Neuroinflammation is a principal driver of brain atrophy and cognitive decline in Alzheimer’s 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.

Authors and Affiliations

Brian G. Rash, PhD¹, Sofya Levitina¹, Jeffrey Botbyl², Chris Conklin, PhD³, Madhura Ingalhalikar, PhD³, Joshua M. Hare, MD¹˒⁴

¹ Longeveron Inc., Miami, FL; ² Provonix, Sewell, NJ; ³ Clario, Part of Thermo Fisher Scientific, Philadelphia, PA; ⁴ University of Miami Miller School of Medicine, Miami, FL.

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.