A PHASE 1, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN HEALTHY VOLUNTEERS TO DETERMINE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF ESCALATING MULTIPLE DOSES OF MMI-0100 OR PLACEBO ADMINISTERED BY PULMONARY DELIVERY - MMI-0100 MAD study

Start Date17 Mar 2016

Sponsor / Collaborator

Moerae Matrix, Inc.

NCT02515396 / Unknown statusPhase 1

A Randomised, Double-Blind, Placebo-Controlled, Two-Way Crossover Study in Healthy Smokers to Investigate the Effect of Inhaled Dosing With MMI-0100 on Airway Inflammation as Assessed in Induced Sputum After Challenge With Inhaled Lipopolysaccharide (LPS)

A Phase 1a, randomized, placebo controlled, two-way crossover study is to determine the effect of inhaled MMI-0100 compared to placebo following LPS challenge on inflammatory markers.

Start Date01 Jul 2015

Sponsor / Collaborator

Moerae Matrix, Inc.

NL-OMON40896 / CompletedNot Applicable

A study to evaluate the pharmacokinetics, safety and tolerability after inhalation of MMI-0100 in healthy subjects; MMI-0100 is an investigational drug developed for the treatment of fibrotic indications. - MMI-0100 SAD study.

Start Date19 Jun 2014

Sponsor / Collaborator

Moerae Matrix, Inc.

100 Clinical Results associated with MMI-0100

100 Translational Medicine associated with MMI-0100

100 Patents (Medical) associated with MMI-0100

Literatures (Medical) associated with MMI-0100

01 Dec 2021·Life SciencesQ3 · MEDICINE

Involvement of mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) in endothelial dysfunction associated with pulmonary hypertension

Q3 · MEDICINE

Article

Author: Zahid Rasool Lone ; Pragya Bharati ; Kashif Hanif ; Jimut Kanti Ghosh ; Kumaravelu Jagavelu ; Himalaya Singh ; Mohammad Shafiq ; Neeraj Kumar Verma ; Matthias Gaestel

AIMSIncreased proliferation, inflammation, and endothelial microparticle (EMP) generation in the pulmonary vasculature lead to endothelial dysfunction in pulmonary hypertension (PH). Interestingly, MK2, a downstream of p38MAPK, is a central regulator of inflammation, proliferation, and EMP generation in cardiovascular diseases. However, the role of MK2 in pulmonary endothelial dysfunction remains unexplored.MAIN METHODSThe Human Pulmonary Artery Endothelial cells (HPAECs) were exposed to hypoxia (1% O₂) for 72 h, and MK2 inhibition was achieved by siRNA treatment. Western blotting, qualitative RT-PCR, immunocytochemistry, flow cytometry and enzyme-linked immunoassays were conducted to study pathological alterations and molecular mechanisms. Neoangiogenesis was studied using cell migration and tubule formation assays. For in vivo study, Male Sprague Dawley rats and MK2 knock-out mice with littermate control were treated with monocrotaline (MCT) 60 mg/kg and 600 mg/kg, respectively (s.c. once in rat and weekly in mice) to induce PH. MMI-0100 (40 μg/kg, i.p. daily for 35 days), was administered in rats to inhibit MK2.KEY FINDINGSMK2 inhibition significantly decreased inflammation, cell proliferation, apoptosis resistance, and improved mitochondrial functions in hypoxic HPAECs. Hypoxia promoted cell migration, VEGF expression, and angiogenesis in HPAECs, which were also reversed by MK2 siRNA. MK2 inhibition decreased EMP generation and increased the expression of p-eNOS in hypoxic HPAECs, a marker of endothelial function. Furthermore, MK2 deficiency and inhibition both reduced the EMP generation in mice and rats, respectively.SIGNIFICANCEThese findings proved that MK2 is involved in endothelial dysfunction, and its inhibition may be beneficial for endothelial function in PH.

01 Apr 2021·HypertensionQ1 · MEDICINE

Inhibition of Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2) is Protective in Pulmonary Hypertension

Q1 · MEDICINE

Article

Author: Shafiq, Mohammad ; Chanda, Debabrata ; Hanif, Kashif ; Gaestel, Matthias ; Iqbal, Hina ; Ghosh, Jimut Kanti ; Jagavelu, Kumaravelu ; Verma, Neeraj Kumar ; Yadav, Pankaj

Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2), downstream to p38MAPK (p38mitogen-activated protein kinase), regulates cellular inflammation and proliferation. So far, the role of MK2 has been studied in many cardiovascular diseases, but it remains unexplored in pulmonary hypertension (PH). Therefore, to investigate the role of MK2 in the PH pathogenesis, human pulmonary artery smooth muscle cells were exposed to hypoxia (1% O 2 ) for 72 hours, and MK2 was inhibited by siRNA. We observed significantly increased MK2 expression, inflammatory cytokines, proliferation, mitochondrial dysfunction, and apoptosis resistance in hypoxic human pulmonary artery smooth muscle cells, which were reversed by treatment with MK2 siRNA. For in vivo studies, male Sprague Dawley rats were treated with monocrotaline (60 mg/kg, SC, once) to induce PH. To inhibit MK2, a peptide MMI-0100 (40 μg/kg, IP daily, 5 weeks for preventive and 3 weeks for curative study) was administered. MMI-0100 treatment decreased right ventricle pressure and hypertrophy, hallmarks of PH, in both preventive and curative study. MMI-0100-treated rats showed better cardiac functions as revealed by 2-dimensional echocardiography study. Furthermore, MMI-0100 reversed pulmonary vascular remodeling and improved pulmonary vascular relaxation in monocrotaline-treated rats. Finally, the above results were confirmed in MK2 knockout mice. 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.

01 Jan 2019·American Journal of Respiratory Cell and Molecular BiologyQ1 · MEDICINE

Mitogen-activated Protein Kinase–activated Protein Kinase 2 Inhibition Attenuates Fibroblast Invasion and Severe Lung Fibrosis

Q1 · MEDICINE

Article

Author: Noble, Paul W. ; Huan, Caijuan ; Jiang, Dianhua ; Liu, Ningshan ; Liu, Xue ; Liang, Jiurong ; Xie, Ting ; Huang, Guanling ; Taghavifar, Forough ; Mena, Jessica Monterrosa ; Kurkciyan, Adrianne ; Zhang, Yanli ; Geng, Yan ; Barron, Vivian

Severe pulmonary fibrosis such as idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix and fibroblast activation. Targeting fibroblast activation has contributed to the development of antifibrotic therapeutics for patients with IPF. Mitogen-activated protein kinase-activated protein kinase 2 (MK2), downstream in the transforming growth factor-β/p38 mitogen-activated protein kinase pathway, has been implicated in inflammatory and fibrosing diseases. Increased concentrations of activated MK2 were expressed in IPF lung and in the mouse bleomycin model of lung fibrosis. The aim of the present study was to determine the role and the mechanisms of MK2 in fibroblast invasion and lung fibrosis. 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. We previously showed that hyaluronan and HAS2 regulate fibroblast invasion and lung fibrosis in vivo. The results of the present study showed that MMI-0100 reduced transforming growth factor-β-induced hyaluronan production in human and mouse fibroblasts in vitro and that HAS2 mediated MK2 activation, suggesting a feed-forward loop in fibroblast activation. More importantly, MK2 inhibition attenuated hyaluronan accumulation and reduced collagen content in bleomycin-injured mouse lungs in vivo. Conditional deletion of MK2 in fibroblasts attenuated 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.

100 Deals associated with MMI-0100

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Idiopathic Pulmonary Fibrosis	Phase 1	US	Moerae Matrix, Inc.	30 Jan 2022
airway disease	Discovery	GB	Moerae Matrix, Inc.	01 Jul 2015
Fibrosis	Discovery	US	Moerae Matrix, Inc.	-

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