Neuroscience translational assays

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Neuroscience translational assays and platforms

Validating compounds in translational assays is considered vital to progression of drug discovery programs. Metrion offers a range of translational, phenotypic neuronal assays and platforms employing 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 assays at Metrion utilise the 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.

Figure 1a. CNS neuron activity on MEA

Figure 1b. CNS neuronal network MEA heatmap

Pain research

To support the discovery and development of novel pain therapeutics, Metrion provides a comprehensive suite of specialised preclinical pain research services. Utilising peripheral neuron phenotypic assays we enable our customers to translate their compounds towards the clinic. We use manual patch-clamp and multi-electrode array (MEA) techniques to answer customer 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).

Native ion channels

Metrion provides native neuronal ion channel assay services using gold-standard manual patch clamp electrophysiology. We have 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.

Figure 2. DRG Ca2+ currents

Neuroscience Resource Library
Validation of antibody toxin fusions against sodium channels

Cardiac toxicity remains the leading cause of new drug safety side-effects. Current preclinical cardiac safety assays rely on in vitro cell-based ion channel assays and ex vivo and in vivo animal models⁽¹⁾. These assays provide an indication of acute risk but they do not always predict the effect of chronic compound exposure, as recently seen with oncology drugs. Therefore, new assays are required to characterise chronic structural and functional effects in human cells earlier in drug discovery. Impedance-based technology can provide more accurate chronic cardiotoxicity measurements in an efficient manner using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Evaluation of hNav1.9 Screening Cascade for Analgesic Drug Discovery

Automated patch clamp enables robust NaV1.9 screening, accelerating discovery of selective sodium channel modulators for pain research.

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