A phase I, first-in-human study to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of MRG-001 in healthy subjects

被引：2

作者：

Ahmadi, Ali R. ^{[1
]}

Atiee, George ^{[2
]}

Chapman, Bart ^{[2
]}

Reynolds, Laurie ^{[2
]}

Sun, John ^{[1
]}

Cameron, Andrew M. ^{[3
]}

Wesson, Russell N. ^{[3
]}

Burdick, James F. ^{[1
]}

Sun, Zhaoli ^{[3
]}

机构：

[1] MedRegen LLC, Baltimore, MD 21205 USA

[2] ICON PLC, San Antonio, TX USA

[3] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD 21205 USA

来源：

CELL REPORTS MEDICINE | 2023年 / 4卷 / 09期

关键词：

CIRCULATING PROGENITOR CELLS; KIDNEY-TRANSPLANT SURVIVAL; HEMATOPOIETIC STEM-CELLS; MOBILIZING AGENTS RESULT; SHORT-TERM TREATMENT; PHARMACOLOGICAL MOBILIZATION; CARDIOVASCULAR OUTCOMES; CD34(+); IMMUNOSUPPRESSION; MORTALITY;

D O I：

10.1016/j.xcrm.2023.101169

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Preclinical studies demonstrate that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a fixed-dose drug combination (MRG-001) improves wound healing, promotes tissue regeneration, and prevents allograft rejection. In this phase I, first-in-human study, three cohorts receive subcutaneous MRG-001 or placebo, every other day for 5 days. The primary outcome is safety and tolerability of MRG-001. Fourteen subjects received MRG-001 and seven received a placebo. MRG001 is safe over the selected dose range. There are no clinically significant laboratory changes. The intermediate dose group demonstrates the most significant white blood cell, stem cell, and immunoregulatory cell mobilization. PBMC RNA sequencing and gene set enrichment analysis reveal 31 down-regulated pathways in the intermediate MRG-001 dose group compared with no changes in the placebo group. MRG-001 is safe across all dose ranges. MRG-001 may be a clinically useful therapy for immunoregulation and tissue regeneration (ClinicalTrials.gov: NCT04646603).

引用

页数：19