Frailty, a syndrome that decreases healthspan in older individuals, lacks effective therapies. We conducted a randomized, dose-finding clinical trial to test whether human bone marrow-derived allogeneic mesenchymal stem cells (MSCs; laromestrocel) improve physical functioning and patient self-reported outcomes in ambulatory individuals with frailty (ClinicalTrials.gov #NCT03169231; N = 148). Laromestrocel infusion results in clinically meaningful, dose- and time-dependent increases in the 6-min walk test (6MWT; primary endpoint) compared with placebo: 63.4 m (95% confidence interval [CI]: 17.1-109.6 m; p = 0.0077) at month 9 and 41.3 m (95% CI: -2.4-84.9 m; p = 0.0635) at month 6. Increased 6MWT distance correlates with PROMIS Physical Function score, and increasing doses of laromestrocel are associated with decreases in soluble (degraded) tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE2), the cognate receptor for the angiopoietins, identifying a potential biomarker of laromestrocel responsiveness. These findings identify a stem cell therapy approach for the management of patients with hypomobility and other features of aging frailty.
- Randomized phase 2b dose-escalation trial of stem cell therapy with laromestrocel for aging frailty
- Jorge G Ruiz - Memorial Healthcare SystemAnthony A Oliva, Jr - Longeveron Inc., Miami, FL, USAKevin N Ramdas - Longeveron Inc., Miami, FL, USAJulian Javier - Naples Community Hospital Healthcare SystemJeffrey Rosen - Clinical Research of South FloridaRobert Perry - Panax Clinical Research, Miami Lakes, FL, USAAntonio Blanco - University of Miami Health SystemPedro Ylisastigui - Clinical Physiology AssociatesJeremy Walston - Johns Hopkins UniversityHidenori Arai - National Center for Geriatrics and GerontologyElena Volpi - The University of Texas Medical Branch at GalvestonAnne B Newman - University of PittsburghBrittany Varnado - Longeveron Inc., Miami, FL, USALisa McClain-Moss - Longeveron Inc., Miami, FL, USAEric Naioti - Longeveron Inc., Miami, FL, USADanial Mehranfard - Longeveron Inc., Miami, FL, USADan Gincel - Longeveron Inc., Miami, FL, USAChao Wang - Product Innovation and Engineering (United States) (United States, Saint James) - LLCMichael J Mintzer - Miami VA Healthcare SystemJoel Danisi - Miami VA Healthcare SystemGeoff A Green - Longeveron Inc., Miami, FL, USAJeffrey Botbyl - Rockwell Automation (United States)Zarin Zainul - Longeveron Inc., Miami, FL, USABrian G Rash - Longeveron Inc., Miami, FL, USAJoshua M Hare - Stem Cell Institute
- Cell stem cell, Vol.33(3)
- CELL PRESS; CAMBRIDGE
- 17
- National Institute of Aging (NIA) of the National Institutes of Health (NIH): R44AG062015
We acknowledge Shirley Arroyo Vizcarrondo for her excellent technical assistance in potency-related MSD experiments. Funding: this study was funded by grant R44AG062015 from the National Institute of Aging (NIA) of the National Institutes of Health (NIH) to Longeveron Inc. This work was completed during D.M.'s employment as a Clinical Scientist at Longeveron Inc. D.M. is currently an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The opinions or perspective expressed herein do not represent the opinions or perspective of D.M.'s employer.
- Interdisciplinary Stem Cell Institute; Leadership Department; Miller School of Medicine; UMMG Dept of Medicine - Geriatric Medicine and Palliative Care
- English
- Journal article
- 41747733
- 991033020069502976