NeuroProof as a contract research organization is a global leader and preferred partner in the field of microelectrode array (MEA)-based phenotypic screening of primary cultures. NeuroProof offers screening services and state-of-the-art mathematical expertise for the phenotypic analysis of test agents on neuronal network activity. The services comprise the growing of primary neuronal cultures on MEA chips, medium throughput screening of test agents, high quality recording of spontaneous and compound-induced network activity, state-of-the-art mathematical analyses, and sophisticated pattern recognition methods. The unique platform is well suited to identify and characterize effects of test agents on neuronal network activity and brain cell functioning.
Our company is specialized in the measurement of neuronal network activity via microelectrode arrays (MEA)-neurochips. We have extensive experience with a range of primary neuronal cell cultures and human neuronal stem cells, and with the recording and mathematical analysis of their spontaneous and compound-induced network activities.
Using our proprietary pattern recognition algorithms, we determine the similarity or difference of a compound to other known compounds.
This allows screening for differentiation from marketed compounds, mimicry of endogenous ligands, and assessment of synergistic effects. The cultures also allow to assess effects on neuronal maturation, synaptogenesis, and regenerative properties as well as assessing the differentiation process of human stem cells cultures.
Selected Publications:
In combination with our MEA analysis or as stand-alone service we provide a complete report for toxicity profiling and safety screening including information about acute or chronic cell viability and cytotoxicity assessed by:
In combination with our MEA analysis or as stand-alone service we provide a complete report for toxicity profiling and safety screening including information about acute or chronic cell viability and cytotoxicity assessed by:
Biochemical validation
Please note: we also prepare cell lysates or fixed cell cultures for you for internal target validation
Electrophysiological validation
In our blocker experiments we block your target-of-interest with a specific blocker (either purchased or blinded) by directly combining with your compounds in a combination experiments.
MEA neurochips are a valuable tool to detect compound effects on neuronal maturation. By use of the MEA-neurochip technology we can directly monitor and characterize maturation of primary mouse or human iPSC-derived network activity in electrically active neuronal networks.
Compound application during maturation (either single or repeated) can affect the onset of spontaneous network activity and the maturation of both individual neurons and whole network characteristics.
We assay the electrical activity patterns of dissociated primary neurons in culture from an early embryonic stage up to 6 weeks of maturation in vitro. The activity fingerprint is described by more than 200 parameters, which allows a sensitive measure for functional maturation and the effects of biologics and chemical compounds thereon to assess effects on synaptogenesis and neurogenesis.
The combination of new compounds with marketed drugs for combination therapy is a promising approach to generate new therapeutic opportunities. The identification of the ideal combination of compounds at an optimal ratio and concentration requires a large number of sensitive tests.
NeuroProof offers a cost-effective and elegant assay to screen compound combinations with a phenotypic read out.
Using NeuroProof's complex data analysis it is possible to detect new and unexpected effects in drug combinations which can be exploited for new therapeutic applications. The precise and highly reproducible data allows the exact determination of optimal ratios of compound mixtures.
Human neuronal stem cell and iPS cell cultures are of high scientific and practical interest in drug discovery, toxicology and for future therapeutic applications. To understand the differentiation process of these stem cell cultures into neurons is an important and complex task and an essential prerequisite for the functional characterization of test compounds in a human cellular background.
Our offer in service and FTE projects
NeuroProof offers its capabilities as a service to analyze customer's electrophysiological data from microelectrode array setups. Customers can benefit from our experience which we gained during the last 15 years. The service includes in vivo and in vitro studies with microelectrode array setups, quality analyses of spike train data and action potential wave form analyses.
After a first inspection of the customer's data we can propose a data analysis concept which fits customer’s requests. If needed, spike train data can be reanalyzed by off line unit separation. Spike train data can be characterized by over 200 activity describing parameters, covering changes in the general activity, the burst structure, the oscillatory behavior, network synchronicity and connectivity. By statistical analysis on the basis of multivariate statistics customers gain reproducible and valid results, supporting their drug discovery and drug development process.
Additionally, NeuroProof offers the development of customized software applications for MEA derived data.
Our services cover all levels of MEA-neurochip data analysis; spike train analysis, multivariate data analysis and building up of in house data bases.
Our contribution to successful drug development for the treatment of neuro degenerative diseases is the offer of relevant in vitro disease models which are based on a functional and phenotypic neuronal readout.
These models can be used for hit identification and validation, lead selection and lead optimization. Due to the functional phenotypic readout, compounds can be investigated independently of their main and potentially unknown target.
We offer the following functional in vitro assays:
Alzheimer:
Functional Abeta42 protection assay: acute treatment of primary hippocampus neurons with Abeta42.
Parkinson:
Functional MPP+ protection assay: challenge of developing primary midbrain dopaminergic neurons by single, low concentration MPP+
We offer these models for the evaluation of your compounds on a fee-for-service basis, providing excellent reproducibility and highly significant results for established reference compounds.
Epilepsy is one of the most common neurological disorders worldwide. The term epilepsy comprises a variety of different syndromes which all have the occurrence of recurrent unprovoked seizures in common.
Although most patients become seizure-free on antiepileptic drugs, about 20-30% of patients continue to have seizures. For those patients no adequate pharmacological treatment is available yet.
Current treatment of epilepsy with drugs relies on symptomatic control of seizures. However, epilepsy cannot be cured with medication, because the mechanisms underlying epileptogenesis are still largely unknown.
NeuroProof has developed an in vitro screening assay to investigate the effects of new classes of antiepileptic compounds. Neuronal networks of embryonic hippocampus neurons grow on MEA chips and develop spontaneous ictal-like activity under certain culture conditions. This activity is characterized by synchronous burst events with a duration of >5 s. Anticonvulsive compounds such as carbamazepine and valproic acid have been shown to resolve these long burst events, while duration of bursts from healthy hippocampus networks are not affected by these compounds.
The NeuroProof technology can also help to understand pro-convulsive compounds such as picrotoxin that induce ictal-like discharges in network activity of frontal cortex cultures. During these ictal discharges bursts are arranged into longer duration burst events that intermit frontal cortex activity.
Using our classification analysis we can predict excitatory or only pro-convulsive potential of test compounds.
NeuroProof offers specific in vitro assays for drug discovery in epilepsy. Human iPSC derived neurons can also be used in these assays to increase translation into humans.
The NeuroProof technology can also help to understand pro-convulsive compounds such as picrotoxin that induce ictal-like discharges in network activity of frontal cortex cultures. During these ictal discharges bursts are arranged into longer duration burst events that intermit frontal cortex activity.
Using our classification analysis we can predict excitatory or only pro-convulsive potential of test compounds. Here we refer to our side effect assays.
We perform phenotypic screening service to assess a compound's action in a micro-circuit including a multitude of physiological relevant receptors with primary neurons or human stem cell-derived cultures growing on a micro electrode array chip. We compare the functional fingerprint of your new compound with profiles of your reference compounds or those in our substance database.
This allows:
We deliver:
The following primary cell cultures are available:
"The technique and quality of MEA were amazing. I would like to work with NeuroProof again."
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