A Randomized, Blinded, Placebo-Controlled Clinical Trial to Evaluate Longeveron Mesenchymal Stem Cell (LMSC) Therapy for Treating The Metabolic Syndrome

The metabolic syndrome (MetS) is a cluster of factors that increases the risks for cardiovascular disease, type 2 diabetes mellitus, and mortality, and currently affects andgt; 40% of US adults. MetS is associated with endothelial dysfunction, decreased circulating endothelial progenitor cells (EPCs), and a pro-inflammatory state. We have made the exciting discovery that therapy with allogeneic mesenchymal stem cells (MSCs) restores endothelial dysfunction and circulating EPCs towards normal the levels, and reduces markers of inflammation. Endothelial function represents a key driver of cardiovascular morbidity and mortality in MetS, and as such, restoring endothelial function could lead to clinical benefits in this patient population. We will conduct a clinical trial using Longeveron-produced allogeneic mesenchymal stem cells (LMSCs) delivered to subjects with MetS. In Phase I of this study, we will perform a dose-escalation Safety Run-In to first establish safety of LMSC therapy in subjects with MetS. After a safety review and approval from an independent data safety monitoring board (DMSB), Phase II of this Fast-Track Study will commence. This will entail a Randomized, Double-Blinded, Placebo-Controlled Phase on 40 subjects with MetS. The following specific aims will be examined.Specific Aim #1: To test the hypothesis that LMSCs are safe to intravenously-administer to subjects withMetS. We will examine for incidence of treatment-emergent serious adverse events (TE-SAEs); bloodchemistry, hematology, coagulation, and urinalysis; and alloimmune reaction and T and B cell subsets toexamine levels of immune activation.Specific Aim #2: To test the hypothesis that intravenously-administered LMSCs will improve endothelialdysfunction and increase circulating EPCs in subjects with MetS. We will examine endothelial dysfunctionusing flow-mediated vasodilation (FMD), and circulating EPCs by colony assays and flow cytometry.Specific Aim #3: To test the hypothesis that intravenously-administered LMSCs will improve systemic markersof inflammation in subjects with MetS. We will use ELISA to examine panels of inflammatory markers.Specific Aim #4: To test the hypothesis that intravenously-administered LMSCs will lead to clinicalimprovement in subjects with MetS. We will examine for changes in glucose control (hemoglobin A1c,fasting glucose, fasting insulin, HOMA), lipid profile (HDL, LDL, triglycerides, cholesterol), blood pressureand cardiac function, physical performance, and subject quality of life. We anticipate that the results of this study will lead to a much needed therapeutic for subjects with MetS. Longeveron is positioned to rapidly advance this program to a pivotal phase III trial if the results prove positive, and to bring this technology to market.The metabolic syndrome (MetS) is a cluster of factors that increases the risks for cardiovascular disease, type 2 diabetes mellitus, and mortality. MetS currently affects over 40% of US adults, and has reached epidemic proportions worldwide; yet highly effective treatments are not available. In this study, a clinical trial will be conducted in which we will use cell therapy to treat MetS (www.ClinicalTrials.gov: identifier NCT02587572). This therapeutic is unique in that it targets 3 major contributors to MetS (endothelial dysfunction, diminished endothelial progenitor cells, and increased inflammation), and we anticipate will provide a highly effective and much needed treatment for MetS.