Recording and Q&A from webinar 'Recent Progress Towards a Potential Treatment for KCNC-1 Related Disorders'
Metrion has extensive ion channel drug discovery experience with indications such as pain, neurodegeneration, psychiatry and epilepsy. Our scientists can advance your project to the next milestone.
We are highly experienced in translational assays, providing quality recordings from relevant tissues expressing your target of interest.
We are also experts in the manual patch clamp technique and offer higher-throughput automated patch clamp services, fluorescence, MEA and manual patch (intracellular/organelle recordings).
Our specialist team of neuroscientists are experts in their field and can help your biology team generate cell lines for your targets.
Our panel of models allow for more accurate prediction of human responses, reduce the risk of late-stage failures and provide a thorough understanding of drug mechanisms.
Ion channel cell lines for both central and peripheral nervous system targets
Primary neuronal cultures, such as dissociated cortical, trigeminal or dorsal root ganglion (DRG) neurons from rodents
CNS drug discovery: Increase the likelihood of successful therapeutic outcomes
Human iPSC-derived neurons
Figure 1. Visual summary of primary neuronal cells used in electrophysiological recordings. A. Rodent dorsal root ganglion (DRG) neuron preparation for manual patch-clamp studies and a bright-field image of dissociated cells seeded on a coverslip. B. DRG action potential responses to low and high prolonged current injections.
A range of assay methodologies is vital in drug discovery because it ensures a thorough evaluation of drug candidates from multiple perspectives. This approach increases the likelihood of identifying effective and safe drugs, reduces the risk of late-stage failures, and supports the overall success of the drug development process. By leveraging diverse assays, researchers can optimize drug candidates, address challenges as they arise, and ultimately bring better therapies to market. Examples of the assays we offer include:
Manual and automated patch-clamp
Fluorescence-based assays
Multi-electrode array (MEA) recordings
Translational assays: central neuronal firing, peripheral neuronal firing, native ion channels
Our neuroscience assays are used to:
Investigate the mechanism of action for pre-clinical compounds in neuroscience research programmes
Confirm compound effects against specific ion channels in native neuronal backgrounds
Address the neurotoxicity of compounds and assess the effects of compounds on a range of excitability parameters
Investigate the effects of compounds on neuronal ion channels and more complex excitatory activity
Screening of your compounds in a neuroscience setting is primarily driven by the fact that they have been designed to modulate CNS or peripheral nervous system targets and signalling pathways, including but not limited to ion channels. Our neuroscience experts can carry out this screening using heterologous cell lines expressing human or rodent neuronal proteins, as well as offering human iPSC-derived neurons and primary rodent cells.
Get insight to selectivity and safety profiling of lead compounds and IND candidates, either as part of an existing screening cascade or because in vivo testing revealed a neurological signal. We have developed and validated an industry-standard rat cortical CNS neuron assay that can reliably detect the seizure-inducing liability of a wide range of reference compounds (as well as serve as a model to profile anti-epileptic drugs). We also have deep expertise with rodent dorsal root ganglion (DRG) sensory neurons which can be used to assess peripheral neurotoxicity.
Studying ion channels on the lysosomal membrane is essential for understanding lysosomal function, cellular homeostasis, and the development of various neurological diseases, such as Parkinson's disease. This research has the potential to uncover new therapeutic targets and improve our knowledge of fundamental cellular processes.
In this video we demonstrate how to perform the lysosomal patch clamp technique to study ion channels on the lysosomal membrane.
Eliana is a two-year-old from Canada with a de novo mutation (V434L) in her KCNC1 gene which encodes for the Kv3.1 channel in central nervous system neurons such as cerebellar neurons and GABAergic interneurons. The mutation manifests as a variety of neurological disorders which can include myoclonic epilepsy and ataxia, developmental epileptic encephalopathy (DEE), or hypotonia, depending on the specific variant.
The KCNC1 Foundation collaborated with Perlara, who approached Metrion Biosciences, where manual and automated (Qube) patch-clamp techniques and Fluorescent Imaging Plate Reader (FLIPR) high-throughput screens (HTS) against the mutant channel were performed to identify hit compounds.
Recording and Q&A from webinar 'Recent Progress Towards a Potential Treatment for KCNC-1 Related Disorders'
This webinar presents the patient perspective, electrophysiological research, and technologies used as we work towards a potential treatment for KCNC1-related disorders.