NeuroProof Expands its Amyotrophic Lateral Sclerosis Assays.
Functional Phenotypic Amyotrophic Lateral Sclerosis Assays.
ALS is a severe disease affecting motor cortex motor neurons, the brain stem, and the spinal cord. NeuroProof suits human iPSC-derived motor neuron cell cultures on microelectrode arrays for a new set of functional phenotypic screening assays. These assays are built with ALS patient-derived cell material. Cell lines with a SOD1 or a C9orf72 mutation are used to mimic a pathological state. The ALS diseased cell lines demonstrate a so-called hyperexcited state, which is also known from clinical or in-vivo data. This translational aspect makes these assays highly confident and predictable. NeuroProof has validated ist ALS assays also with known positive and negative controls. BMAA, β-N-methylamino-L-alanine, is one such negative control, which is suspected of causing ALS.
The etiology of ALS is very complex, and the understanding of disease mechanisms is incomplete. Astrocytes play an essential role in the concert of disease causes. Therefore NeuroProof uses astrocytes with a C9orf72 mutation as co-culture to the C9orf72 motor neurons. The C9orf72 astrocytes showed a strong toxic effect in this setting.
NeuroProof performs more and more customer projects with ist ALS assays in different variants. Surprisingly it seems that riluzole has in all of these assays a positive effect. So riluzole is taken as the standard positive control. NeuroProof is now assessing biomarkers of ALS as TDP-43 and non-ATG related dipeptide in the C9orf72 mutated cells. The C9orf72 mutation also has significance in frontotemporal dementia.
In a video we present an experimental scheme with a repeated compound application that allows the screening for compounds acting not on ionotropic targets.
Find out more about these assays here.
Updated Substance Database
NeuroProof has Updated its Substance Database
NeuroProof has updated its substance database with electrophysiological profiles of neuroactive compounds. Electrophysiological profiles were measured with the Axion MAESTRO pro system and 48 well plates and frontal cortex cultures from mice. Our substance database sheet lists more than 70 compounds. For each substance, a data-sheet with 12 spike train parameters of concentration-response curves is available on request, see at https://www.neuroproof.com/en/Substance-Database.html.
New Fragile X Syndrome Assay
NeuroProof Offers a New Screening Assay for a Rare Disease
NeuroProof has developed a new assay to screen compounds as potential novel Fragile X Syndrome treatments. For this, NeuroProof has developed a new assay based on iPSC derived glutamatergic cells that were generated from a patient cell line with FSX.
FSX is a serious genetic disease-causing cognitive impairment with a prevalence of 1:5000 in males and 1:8000 in females. Up to date, any effective treatment is available. FSX is caused by multiple expansion oft he CGG triplet in the FMR1 gene. Normally 5 to 55 such repeats are found in healthy controls. FXS patients have 200 and more of such repeats. These different repeat numbers induce different silencing rates of the FMR1 protein, and in combination with different general genetic backgrounds, treatment responses differ strongly, which makes the development for treatments of this not easier.
The advantage of NeuroProof’s approach is that with a disease model from iPSC derived neurons cultivated on a microelectrode array, the electrophysiological function of single neurons can be monitored. This assay allows a highly predictive compound screen, which is closely related to a patient‘s brain physiology.
NeuroProof is working with leading pharmaceutical companies to perform drug screening to find new cures for this serious disease.
Find more about this assay here.
Novel Schizophrenia Assay
NeuroProof Presents at the 5th Annual Neuroscience R&D Technologies Conference in London on October 4, 2019, its new Schizophrenia Assay
Dr. Olaf Schroeder will present NeuroProof’s novel Schizophrenia assay. Schizophrenia is a mental disorder, that is difficult to model in an in vitro assay. NeuroProof has successfully translated electro-physiological symptoms of this debilitating disease in a functional assay with microelectrode arrays. Olaf Schroeder will present this new technology and first results with compound testing. The new technology uses NeuroProof’s newly developed analysis method of the E/I balance. With this a precise assessment of the excitatory and inhibitory neuronal circuitry balance, which is also a key issue in schizophrenia is now possible in a living neuronal cell system.
NeuroProof Offers New Product Line with Primary Neuronall Cells
Rostock August 26th 2019 NeuroProof expands its product portfolio
New Products with Primary Neuronal Cells from NeuroProof.Systems will start soon.
We have started a new website: NeuroProof.Systems. Services of customer specific cell preparations are scheduled to commence in the 4th quarter 2019. First products are fresh primary mouse cells best suited for scientific research in toxicology, cytology and other fields in CNS research. We will also offer whole brain tissues and pre-cultivated microelectrode arrays. Our customers will participate from NeuroProof’s experience in cell culture technologies with these new offers. New website here NeuroProoof.Systems.
NeuroProof poster at SLAS 2019
SLAS meeting 2019 in Washington DC, Feb 2-6
In collaboration with BrainXell, a Madison, Wisconsin US Company, NeuroProof GmbH presents its functional phenotypic screening assay using human motor neurons on in vitro disease modeling using human motor neurons derived from patients who have either amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy (SMA).
Related neuronal activities were functionally phenotyped with NeuroProof's artificial intelligence analyses of multi-well microelectrode assay (MEA) data. Be invited to discuss our medium throughput assay for rare diseases with the experts or get a free poster copy (contact us after the meeting).
Meet NeuroProof at the SfN 2018
San Diego Nov. 3rd-7th 2018, booth 3108
NeuroProof presents its newest developments in functional phenotypic screening combined with multivariate and artificial intelligence analysis methods. We are seeking for collaboration partners and are glad to help to make your drug discovery projects a real success. Visit our poster to discuss new collaboration projects. Get an update on our service offers and models for neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Schizophrenia, Epilepsy, rare diseases and for safety pharmacology.
Get the chance to discuss our latest developments with our CEO Olaf H.-U. Schroeder and our Project Manager Benjamin Bader at booth 3108.
Visit our poster:
November 3, 2018, 1:00 PM, Session: Poster: 052 - Neuromuscular Diseases: Motor Neuron Disease: In Vitro Studies
Poster 052.16. Phenotypic functional in vitro screening of patient iPSC-derived motor neurons used for in vitro HTS disease modeling with AI-based analysis of micro electrode array data
Functional in vitro HTS seizure prediction with human and mouse neurons growing on microelectrode arrays analyzed by artificial intelligence-based methods
Visit the NeuroProof poster at the SPS annual meeting 20018 Sep. 30th – Oct. 3rd 2018 in Washington D.C.
Facing seizurogenic effects in drug discovery leads to significant attrition rates which partly is due to the lack of suitable in vitro test systems. Further, presently used brain slice or behavior assays for predicting seizure risk are accompanied by low throughput and high demand for animal tests and the fact that results from rodent tests not always translate into the human situation. Microelectrode arrays (MEAs) with dissociated neurons are currently under investigation using both mouse and human induced pluripotent stem cells (hiPSC) to serve as an alternative to current state-of-art. Contrasting mouse and human neuronal in vitro MEA systems therefore is needed to improve clinical translation.
We cultured primary mouse cortex and hiPSC neurons on multiwell microelectrode arrays. After 3-4 weeks in vitro, we tested known seizurogenic compounds and analyzed the recorded spike trains by computing more than 200 parameters to describe the compound’s functional phenotype. The established fingerprints reveal a common seizure-specific phenotype identified by AI-based classification analysis. Using this classifier, we compare the predicted seizure risk for several clinical compounds in a concentration-dependent manner between human iPSC-derived neuronal networks and those from functionally mature primary mouse cortical networks.
In summary, our data underlines the common understanding that the MEA technology allows dissecting the functional differences between hiPSC- and mouse neuronal culture models. Here, we present a tool for investigating and comparing the safety margin of novel drug candidates in rodent and human cells and thereby complement the toolbox for prediction of functional seizurogenic risk assessment.
Meet NeuroProof at the ECNP 6-9.10.2018 in Barcelona
The potentials and limitations of personalized induced pluripotent stem cell (iPSC) models in neuropsychiatry
Meet NeuroProof at a Brainstorm Meeting at the international conference ECNP 6-9.10.2018 in Barcelona
The Brainstorm Meeting will be held on Sunday 7th of October 2018
This brainstorm meeting will be organized by Prof. Edna Grünblatt from University Hospital of Psychiatry Zurich and Dr. Olaf Schröder from NeuroProof GmbH, Germany.
Within this meeting, the enormous progress in establishing disease models for psychiatric disorders with iPSC based technologies and functional phenotypic screening will be addressed.
Practical experiences with such models will be presented.
We will be happy to meet you at the ECNP and to discuss with you this fascinating topic.
Neuropsychiatry disorders such as autism, schizophrenia, bipolar and attention-deficit hyperactivity disorder (ADHD) have polygenetic, neuro-immunological, environmental and developmental causes, with complex etiology to be yet revealed. Recent advancement in research (that includes patient-specific disease modelling, new methods of treatment monitoring, personalized medicine, and new differential diagnostic markers) opened new opportunities to study such disorders and differentially diagnose and predict treatment response: in this brainstorming session, the speakers will discuss the potentials and limitations of induced pluripotent stem cells (iPSC) in neuropsychiatry. Since Yamanaka and colleagues generated the first iPSC, many attempts to generate these cells also from patients with psychiatric diseases were made. The generation of patient- and disease-specific iPSC cultures, following standardized and reproducible protocols, and the use of these cultures in drug discovery still require rigorous validation of the methods and continuous improvement of protocols and read outs. iPSC models allow imaging, molecular, cellular, biochemical and functional read outs to investigate neurodevelopmental trajectories and to model the course of the disease development while monitoring treatment success. One of such methods is the functional label-free read outs using microelectrode arrays (electrophysiology), to correlate patient diagnostic outcomes with outcomes generated from iPSC models. The discussion will focus on different topics concerning the use of iPSC in neuropsychiatry, such as brain region-specific models, co-culturing with glial cells, organoids, quality markers, the influence of epigenetic disturbances and the use of genetic modifications.
Meet NeuroProof at the ISSCR 2018
Melbourne, June, 20-23
In collaboration with BrainXell, a Madison, Wisconsin US Company, NeuroProof GmbH presents brand new results on in vitro disease modeling using human motor neurons derived from patients who have either amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy (SMA).
Related neuronal activities were functionally phenotyped with NeuroProof's artificial intelligence analyses of multi-well microelectrode assay (MEA) data. Be invited to discuss our new disease models with the experts or get a free poster copy (contact us after the meeting).