MMI-0100 / Moerae Matrix, Teva - LARVOL DELTA

Mechanism of Regulating MK2 to Improve Bone Marrow Inflammatory Damage after Hematopoietic Stem Cell Transplantation (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi) - "MMI-0100 can ameliorate bone marrow inflammatory injury after allo-HSCT and may act by reducing NLRP3 expression to promote M2 polarization."

Journal • Bone Marrow Transplantation • Inflammation • Transplantation • CASP1 • IL18 • IL1B • NLRP3

Involvement of mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) in endothelial dysfunction associated with pulmonary hypertension. (PubMed, Life Sci) - "These findings proved that MK2 is involved in endothelial dysfunction, and its inhibition may be beneficial for endothelial function in PH."

Journal • Cardiovascular • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • NOS3

Inhibition of Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2) is Protective in Pulmonary Hypertension. (PubMed, Hypertension) - "To inhibit MK2, a peptide MMI-0100 (40 μg/kg, IP daily, 5 weeks for preventive and 3 weeks for curative study) was administered...MK2 knockout mice, received 600 mg/kg monocrotaline, subcutaneous weekly for 5 weeks, failed to develop PH and showed no increase in right ventricle pressure and hypertrophy. This study, therefore, proved that MK2 is involved in PH, and its inhibition may be a novel target for PH treatment."

Journal • Cardiovascular • Hypertension • Immunology • Inflammation • Metabolic Disorders • Pulmonary Arterial Hypertension • Respiratory Diseases

Intranasal MMI-0100 Attenuates Aβ- and LPS-Induced Neuroinflammation and Memory Impairments via the MK2 Signaling Pathway. (PubMed, Front Immunol) - " MMI-0100 attenuates Aβ- and LPS-induced neuroinflammation and memory impairments via the MK2 signaling pathway. Meanwhile, these data suggest that the MMI-0100/MK2 system may provide a new potential target for treatment of AD."

Journal • Alzheimer's Disease • CNS Disorders • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Respiratory Diseases

Moerae initiates lipopolysaccharide (LPS) challenge study of inhaled MMI-0100 for pulmonary disease following encouraging safety and tolerability observed in single ascending dose Phase 1 study (PRNewswire) - "Moerae Matrix Inc. announced today the initiation of its second Phase 1 clinical trial with MMI-0100...The study, conducted in the United Kingdom, is a double-blind, two-way cross-over design lipopolysaccharide (LPS) challenge study further evaluating the safety and tolerability of MMI-0100 when given via inhalation to healthy subjects who smoke. The effect of MMI-0100 on biomarkers of inflammation will also be explored."

Trial initiation date • Fibrosis

Peptide-mediated inhibition of MK2 ameliorates bleomycin-induced pulmonary fibrosis (Am J Respir Cell Mol Biol) - PMID: 23470623; "MK2i significantly abrogated collagen deposition, myofibroblast differentiation and activated MK2 expression. MK2i also decreased circulating TNF-α and IL-6 levels and modulated local mRNA expression of pro-fibrotic cytokine il-1β, matrix-related genes-col1a2, col3a1, lox, and TGF-beta family members including smad3, serpine1 (pai1) and smad6/7...Peptide mediated inhibition of MK2 impacts both inflammatory and fibrotic responses and thus may be a promising therapeutic target for IPF."

Preclinical • Fibrosis

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway. (PubMed, Molecules) - "The anti-inflammatory effects of MMI-0100 on DSS-induced colitis were achieved by down-regulating the phosphorylation level of MK2, IκBα and p65 protein. The current study clearly demonstrates a protective role for MMI-0100 in experimental IBD."

IO Biomarker • Journal • Preclinical

MK2 Inhibition Attenuates Fibroblast Invasion and Severe Lung Fibrosis. (PubMed, Am J Respir Cell Mol Biol) - "Our results showed that an MK2 inhibitor (MMI-0100) was able to inhibit the invasive capacity of lung fibroblasts isolated from patients with IPF, as well as fibroblasts isolated from both wild-type mice and mice with overexpressing hyaluronan synthase 2 (HAS2) in the myofibroblast compartment. Conditional deletion of MK2 in fibroblasts attenduated bleomycin-induced lung fibrosis. These data provide evidence that MK2 has a role in fibroblast invasion and fibrosis and may be a novel therapeutic target in pulmonary fibrosis."

Journal

MMI-0100 ameliorates lung inflammation in a mouse model of acute respiratory distress syndrome by reducing endothelial expression of ICAM-1. (PubMed, Drug Des Devel Ther) - "The mRNA and protein expression of ICAM-1 in the LPS group was significantly higher than in the control group in mouse PMVECs, and the ICAM-1 level was reduced after the administration of MMI-0100. These data indicate that MMI-0100 ameliorates lung inflammation in a mouse model of ARDS by reducing endothelial expression of ICAM-1."

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