@article{9dce72132bd24e989f9ff7afc82451fb,
title = "Results and insights from a phase I clinical trial of Lomecel-B for Alzheimer's disease",
abstract = "Hypothesis: We hypothesized that Lomecel-B, an allogeneic medicinal signaling cell (MSC) therapeutic candidate for Alzheimer's disease (AD), is safe and potentially disease-modifying via pleiotropic mechanisms of action. Key Predictions: We prospectively tested the predictions that Lomecel-B administration to mild AD patients is safe (primary endpoint) and would provide multiple exploratory indications of potential efficacy in clinical and biomarker domains (prespecified secondary/exploratory endpoints). Strategy and Key Results: Mild AD patient received a single infusion of low- or high-dose Lomecel-B, or placebo, in a double-blind, randomized, phase I trial. The primary safety endpoint was met. Fluid-based and imaging biomarkers indicated significant improvement in the Lomecel-B arms versus placebo. The low-dose Lomecel-B arm showed significant improvements versus placebo on neurocognitive and other assessments. Interpretation: Our results support the safety of Lomecel-B for AD, suggest clinical potential, and provide mechanistic insights. This early-stage study provides important exploratory information for larger efficacy-powered clinical trials.",
keywords = "Alzheimer disease, Lomecel-B, anti-inflammatory agents, biological therapy, bone marrow mesenchymal stem cell, clinical trial, cytokines, hippocampus, human bone marrow, inflammation, inflammation mediators, interleukins, medicinal signaling cell, mesenchymal stem cell, mesenchymal stromal cell, multipotent stem cells, neuroimaging, neuroinflammatory diseases, randomized controlled trial, regenerative medicine, vascular, vascular endothelial cell growth factor",
author = "Mark Brody and Marc Agronin and Herskowitz, {Brad J.} and Bookheimer, {Susan Y.} and Small, {Gary W.} and Benjamin Hitchinson and Kevin Ramdas and Tyler Wishard and McInerney, {Katalina Fern{\'a}ndez} and Bruno Vellas and Felipe Sierra and Zhijie Jiang and Lisa Mcclain-Moss and Carmen Perez and Ana Fuquay and Savannah Rodriguez and Hare, {Joshua M.} and Oliva, {Anthony A.} and Bernard Baumel",
note = "Funding Information: This research was supported by two grants from the Alzheimer's Association awarded to Longeveron (AAO, principal investigator). AAO, BH, LM‐M, KR, and JH received partial salary support from these grants. MB, MA, BJH, and BB were clinical investigators on the clinical trial of this study, to which institutional payments were made by Longeveron, partially using funds from these grants. TW received a consulting fee from Longeveron that was pre‐approved by his institution to perform MRI analyses, and paid in part by one of these grants. FS, BV, SB, MB, MA, and BJH serve as members of Longeveron's Alzheimer's Disease Program Steering Committee, and for which no support was made from these grants. AAO, BH, LM‐M, KR, and JH are affiliated with Longeveron Inc., and receive salary support and stock options from Longeveron. In addition, the authors report the following over the past 36 months. MB has contracted with Biogen, Lilly Cerevel, UCB, AgeneBio, Cortexyme, Genentech, Roche, NIH, Cognito, BioIVT, Athira, Novartis, EISAI, ABBVIE, Cassava, Biohaven, Athira, Alector, GreenValley, Janssen, SAMUS, Vaccinex (institutional payments made). He also serves on advisory boards for both Lilly and Biogen, and has been a paid consultant for Biogen. MA has contracted with Biogen and Mededicus, and is President‐elect (2022) of the American Association for Geriatric Psychiatry. SB has received (in the form of institutional support) grants from the Alzheimer's Association (Zenith award), NICHD (2 center grants, 1 network), NIA (multi‐site, site PI), NIDA (multi‐site, site PI), and NIMH (multi‐site; site PI), which were not used for this study. Her institution has also received payments for patent from MS Cohen on a signal process algorithm unrelated to the current paper, and receives direct consulting fees on MRI research from the Pacific Neuroscience Institute, and received a speaker honorarium from the Society of Biological Psychiatry. GS has contracted or consulted for the AARP, Acadia, Allergan, Avanir, Biogen, Genentech, Gerontological Society of America, Handok, Herbalife, Home Care Assistance, Longeveron, McCormick Spice Institute, Medscape, Reckitt Benckiser, Roche, Theravalues, and WebMD. He has also received grant support from NIH (Columbia University Multi‐site Clinical Trials), and is on a UCLA patent for FDDNP‐PET. BH is a co‐investigator on a Maryland Stem Cell Research Fund grant unrelated to this study, and is a co‐inventor on a provisional patent related to Lomecel‐B. BV has received grants from the Ton Institution, Lilly, Pfizer, and Pierre Fabre Merci outside of the presented work and provided to the institution, has received consulting fees from Lily, Biogen, Roche, and Longeveron outside of this work. FS has received consulting fees from Indiana University, and from the Fisabio Conferences, all paid directly to him. JMH is a co‐founder, Chief Science Officer, and board member of Longeveron Inc. This relationship is reported to the University of Miami, and a management plan is in place. JMH is inventor of intellectual property licensed to Longeveron. Longeveron has paid license fees to the University of Miami through an Exclusive license fee, and as a university faculty member, he has received an institutionally designated share of these fees. He is a named co‐inventor on provisional patents submitted by Longeveron, and an investigator on grants from the National Institutes of Health and Department of Defense unrelated to this research (institutional payments made). He has also served on two DSMBs (one for the National Institutes of Aging; the other for the National Eye Institute), has received support for presentation at the American Heart Association (covered by an NIH grant to University of Miami), and is affiliated with the Heart Failure Society of America. AAO has received grant support as principal investigator from the National Institute of Aging (two awards) and Maryland Stem Cell Research Fund (three awards) that were unrelated to this research (institutional payments made). He has received travel/accommodations support from the National Institutes of Health for the Geroscience Summit III, and from the University of the West Indies (The Bahamas) for presentations (paid directly to him). He is also a co‐inventor on provisional patents submitted by Longeveron. The University of Miami is an equity owner in Longeveron, which has licensed intellectual property from the University of Miami. Publisher Copyright: {\textcopyright} 2022 Longeveron Inc. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Wiley Periodicals LLC.",
year = "2022",
doi = "10.1002/alz.12651",
language = "English (US)",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
}