Neuroscience Translational Assays
Metrion offers a set of reliable and reproducible translational neuroscience assays to demonstrate the efficacy, selectivity, potency and neurotoxic liability of your therapeutic compounds.
Table of Contents
Introduction To Neuroscience Translational Assays And Platforms
Validating compounds in translational assays is vital to progressing your drug discovery program. Metrion offers a range of translational, phenotypic neuronal assays and platforms employing native rodent and human iPSCs from the peripheral and central nervous system (CNS). We mainly focus on electrophysiological readouts, using manual patch (voltage and current clamp) and multi-electrode array (MEA) platforms to record changes in single cell and neuronal network activity, and determine the effects of media, cell biology modulators, signalling pathways and test compounds.
These assays often need to be specifically designed for your translational neuroscience needs, please contact us with your requirements using the buttons below.
Central Neuronal Firing
Central neuron phenotypic assay platforms at Metrion include manual patch -clamp and multi-electrode array (MEA) techniques, which can help to establish compound potency and efficacy for purposes of target validation, target engagement and species selectivity in native cells and tissues. Single cell patch clamp recordings of passive membrane properties, action potential (AP) firing, synaptic activity and underlying ionic currents are useful for testing specific effects and mechanism-of-action (MOA) studies of compounds on protein targets and signalling pathways, such as those involved in major CNS diseases such as epilepsy, depression, anxiety and neurodegeneration. In contrast, MEA recordings allow interrogation of effects both at the single neuron level, and from larger scale networks of interconnected neuronal and glial cell types.
Physiological activity is monitored from native tissue such as rodent cortical neurons (MEA burst & heat map as shown in Fig. 1), or from other CNS cell types such as those derived from human stem cells which could bear patient-derived disease mutations or be genetically engineered to create translational ‘disease-in-a-dish’ phenotypic assays.
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Peripheral Neuronal Firing
Metrion utilise peripheral neuron phenotypic assays to enable our customers to translate their compounds towards the clinic. We use manual patch-clamp and multi-electrode array (MEA) techniques to answer client questions about target validation, target engagement and species selectivity. Single cell patch clamp recordings of passive membrane properties, action potential (AP) firing, synaptic activity and underlying ionic currents are useful for testing specific effects and mechanism-of-action (MOA) studies of test compounds on protein targets and signalling pathways, such as those involved in pain and inflammation. In contrast, MEA recordings allow study of effects both at the single neuron level, and those resulting from more complex interactions in mixed cultures of peripheral neuronal and glial cell types.
Physiological activity can be monitored from native tissue such as rodent dorsal root ganglia (DRG) or human DRG (shown in Fig. 2).
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Native Ion Channels
Metrion has extensive experience of developing screening assays against specific endogenous ion channels expressed within native neurons to provide further compound validation. Determination of the pharmacology and selectivity of compounds in the intact cell milieu can help to bridge the translational gap between in vitro assays and in vivo applications. Assays can be designed specifically for your needs to explore the mechanism of action of compounds, so talk to us about your exact requirements.
Neuronal Translational Assays Resource Library
- Development of Native and Stem Cell-Derived Electrophysiological Assays for Neurotoxicology Screening and Translational Drug Discovery. SPS Berlin 2017 poster 142.
- Profiling endogenous sodium channels in the ND7-23 neuroblastoma cell line: implications for use as a heterologous ion channel expression system and native tissue model suitable for automated patch clamp screening. Royal Society for Chemistry Ion Channel Symposium, March 2016.
- Metrion Biosciences: high quality ion channel drug discovery service provider. Milner Therapeutics Symposium, Cambridge, 2019
- The role of Nav1.7 in human nociceptors: insights from human induced pluripotent stem cell-derived sensory neurons of erythromelalgia patients.
- Characterization of Endogenous Sodium Channels in the ND7-23 Neuroblastoma Cell Line: Implications for Use as a Heterologous Ion Channel Expression System Suitable for Automated Patch Clamp Screening.
- Voltage-clamp and current-clamp recordings from mammalian DRG neurons.
- Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons.
- The role of sodium channels in neuropathic pain.
- A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons.
- Marc Rogers (Metrion Director and CSO) outlines the benefits of targeting ion channels for pain and some of the hurdles in developing successful ion channel modulators.
- Marc Rogers (Metrion Director and CSO) takes part in a collaborative webinar with Nanion Technologies entitled “Validation and optimization of automated patch clamp voltage-gated Ca2+ channel assays”.
Neuronal Translational Assays Technologies
- Conventional manual patch clamp electrophysiology
- Plate-based microelectrode array techniques
Let’s work together
What are your specific assay needs?
If you have any questions or would like to discuss your specific assay requirements, we will put you directly in touch with a member of our scientific team.