Delving into the Latest Updates on EmtinB(NeuroScientific Biopharmaceuticals) with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms-

Target

MT2

Action

modulators

Mechanism

MT2 modulators(metallothionein 2A modulators)

Therapeutic Areas

Nervous System DiseasesEye DiseasesRespiratory Diseases+ [2]

Active Indication

Alzheimer DiseaseGlaucomaPulmonary Fibrosis+ [2]

Inactive Indication-

Originator Organization

Neuroscientific Biopharmaceuticals Ltd.

Active Organization

Neuroscientific Biopharmaceuticals Ltd.

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

AbstractMetallothioneins I and II (MTI/II) are metal‐binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the β‐domain of MT‐II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate the neuroprotective effect of EmtinB in the in vitro and in vivo models of kainic acid (KA)‐induced neurotoxicity. We show that EmtinB passes the blood–brain barrier and is detectable in plasma for up to 24 hr. Treatment with EmtinB significantly attenuates seizures in C57BL/6J mice exposed to moderate (20 mg/kg) and high (30 mg/kg) KA doses and tends to decrease mortality induced by the high KA dose. Histopathological evaluation of hippocampal (CA3 and CA1) and cortical areas of mice treated with 20 mg/kg KA shows that EmtinB treatment reduces KA‐induced neurodegeneration in the CA1 region. These findings establish EmtinB as a promising target for therapeutic development. © 2009 Wiley‐Liss, Inc.

01 Aug 2009·European Journal of Cell BiologyQ3 · BIOLOGY

Peptides modeled after the α-domain of metallothionein induce neurite outgrowth and promote survival of cerebellar granule neurons

Q3 · BIOLOGY

Article

Author: Vladimir Berezin ; Elisabeth Bock ; Malene Ambjørn ; Johanne Wirenfeldt Asmussen

Metallothionein (MT) is a metal-binding protein capable of preventing oxidative stress and apoptotic cell death in the central nervous system of mammals, and hence is of putative therapeutic value in the treatment of neurodegenerative disorders. Recently, we demonstrated that a peptide modeled after the beta-domain of MT, EmtinB, induced neurite outgrowth and increased neuronal survival through binding to receptors of the low-density lipoprotein receptor family (LDLR). The present study identified two MT alpha-domain-derived peptide sequences termed EmtinAn and EmtinAc, each consisting of 14 amino acids, as potent stimulators of neuronal differentiation and survival of primary neurons. In addition, we show that a peptide derived from the N-terminus of the MT beta-domain, EmtinBn, promotes neuronal survival. The neuritogenic and survival promoting effects of EmtinAc, similar to MT and EmtinB but not EmtinAn, were dependent on the functional integrity of LDLR. Moreover, EmtinAn and EmtinAc induced activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB/Akt). We suggest that multiple functional sites of MT serve to cross-link MT receptor(s), thereby transducing signals leading to an increase in neurite outgrowth and survival.

01 Jan 2008·Journal of Neurochemistry

Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low‐density lipoprotein receptor family

Article

Author: Johanne W. Asmussen ; Elisabeth Bock ; Vladimir Berezin ; Malene Ambjørn ; Kamil Gotfryd ; Mats Lindstam ; Milena Penkowa ; Vladislav V. Kiselyov ; Søren K. Moestrup ; Christian Jacobsen

AbstractAccumulating evidence suggests that metallothionein (MT)‐I and ‐II promote neuronal survival and regeneration in vivo. The present study investigated the molecular mechanisms underlying the differentiation and survival‐promoting effects of MT and a peptide modeled after MT, EmtinB. Both MT and EmtinB directly stimulated neurite outgrowth and promoted survival in vitro using primary cultures of cerebellar granule neurons. In addition, expression and surface localization of megalin, a known MT receptor, and the related lipoprotein receptor‐related protein‐1 (LRP) are demonstrated in cerebellar granule neurons. By means of surface plasmon resonance MT and EmtinB were found to bind to both megalin and LRP. The bindings were abrogated in the presence of receptor‐associated protein‐1, an antagonist of the low‐density lipoprotein receptor family, which also inhibited MT‐ and EmtinB‐induced neurite outgrowth and survival. MT‐mediated neurite outgrowth was furthermore inhibited by an anti‐megalin serum. EmtinB‐mediated inhibition of apoptosis occurred without a reduction of caspase‐3 activity, but was associated with reduced expression of the pro‐apoptotic B‐cell leukemia/lymphoma‐2 interacting member of cell death (BimS). Finally, evidence is provided that MT and EmtinB activate extracellular signal‐regulated kinase, protein kinase B, and cAMP response element binding protein. Altogether, these results strongly suggest that MT and EmtinB induce their neuronal effects through direct binding to surface receptors belonging to the low‐density lipoprotein receptor family, such as megalin and LRP, thereby activating signal transduction pathways resulting in neurite outgrowth and survival.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Preclinical	Australia	Neuroscientific Biopharmaceuticals Ltd.	30 Jan 2022
Glaucoma	Preclinical	Australia	Neuroscientific Biopharmaceuticals Ltd.	30 Jan 2022
Pulmonary Fibrosis	Preclinical	Australia	Neuroscientific Biopharmaceuticals Ltd.	30 Jan 2022
Multiple Sclerosis	Discovery	Australia	Neuroscientific Biopharmaceuticals Ltd.	30 Jan 2022
Optic Atrophy	Discovery	Australia	Neuroscientific Biopharmaceuticals Ltd.	30 Jan 2022

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