In vitro Disease Models
Functional Phenotypic Screening
Functional and phenotypic screening has enormous importance in CNS drug discovery. NeuroProof offers in vitro disease models which incorporate the advantages of the phenotypic screening approach. In vitro CNS disease models contain complex neuronal cell cultures and are a real alternative to animal models in the early phases of drug development and compound profiling.
Predictive data play the most crucial role. We need assays containing more physiologically significance. The need for physiological relevance in CNS drug screening has driven the industry to strengthen the position of cell-based assays. Also, phenotypic screening is the preferred choice compared to target based drug discovery, especially in CNS. The combination of functional and phenotypic screening allows the discovery of new modes of actions for innovative disease-modifying treatments for severe CNS diseases.
For the functional screening of neurogenesis and synaptogenesis, connective behavior and neurodevelopmental processes and neuro-immunological aspects, microelectrode MEA screenings is state of the art. MEA screening of electrical activity patterns of complex cell culture models delivers the electrophysiological function by action potentials, displaying the function of the brain.
NeuroProof's functional phenotypic screening services can be used for initial compound screens or as part of secondary screening campaigns to validate results from target-based approaches as an additional choice.
In Vitro Models for Neurological and Psychological Diseases
NeuroProof's in vitro disease models cover most areas of CNS diseases, neurodegenerative and neurological diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy and psychological and neurobeahvioral diseases, schizophrenia, autism and depression, to name a few.
NeuroProof also uses classical approaches of rescue assays to mimic CNS diseases, which are part of our technology portfolio. The appropriate time for stimulation together with optimal concentration to stimulate are the essential parameters for assay optimization.
Subtle stimulations with disease modeling compounds at sub-toxic concentration mimics early disease pathologies and allows the screening of compounds, which revert the progress of the disease. Our Abeta assay supports this concept for Alzheimer’s disease and the MPP+ assay for Parkinson’s disease.
NeuroProof is your Expert Company for the screening of small molecules, biologicals and also of endogenous compounds.
Complex Neuronal Cell-Based Assays
Sophisticated highly efficient neuronal cell models require a minimum of volume. A tradeoff between psychological relevance and high throughput capabilities are an essential decision point for the best outcome for screening projects.
In the preferred case, the desired neuronal cell cultures comprise multiple kinds of neurons including excitatory, inhibitory and modulatory neurons as well as different glia cells. In total, we can model complex mechanisms of action as they are performed in the brain.
In vitro models for specific CNS diseases include appropriate tissue or a combination of different tissue cultures from selective brain regions. NeuroProof has the long-term expertise for a wide range of co-culture cell systems.
iPSC Based Models with Patient Derived Cells
One of the most significant advances in cell-based assays has been the development of high-content screening technologies and iPSC disease modeling.
As collaboration projects with prominent partners, NeuroProof has developed diseased patients derived iPSC neuronal cell models to create unique innovative, adaptive and responsive solutions in the areas of human health and nutrition.
Starting from patient-derived models, NeuroProof has implemented in vitro disease models for rare diseases such as Niemann Pick Type C1, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and others.
NeuroProof offers complete project management solutions for the development of in vitro disease models, based on cell sourcing from patients, iPSC generation, genetic modification, cell differentiation. Our support includes the required model validation steps and screening campaigns.
High Content Screening and Artificial Intelligence Analytics
Bio-molecular analytics are part of assay validation and are mandatory for valuable in vitro models. Our analytical tools facilitate the best possible outcome of screening assays. Artificial intelligence includes the process of data compressing, reducing multivariate data to univariate parameters, the effect scores. They allow the ranking of compounds according to their therapeutic value.
These effect scores are surrogates for therapeutic effects. NeuroProof validates these effect scores and correlates them with clinical findings to maximize their physiological relevance and value. The NeuroProof effect scores express the most significant meaning besides a wide range including affected molecular elements of complex signal pathways.
NeuroProof understands that the traditional high content screening as imaging screening alone is not the ultimate solution. High content functional and high content structural and molecular screening enabling the identification of complex phenotypes.
Some models can be outlined in primary mouse cultures and human iPSC derived cultures. The comparison of the models from different species is expected to increase the physiological relevance, mainly when comparable effects can be identified. Complex mechanisms as homeostasis and feedback loops can often compensate effects, which are elucidated from target-based approaches.
|Indication||Model Type||Cell Culture|
|Alzheimer’s Disease||Amyloid beta addition||Mouse, human iPSC neurons|
|Streptozotocin addition||Mouse, human iPSC neurons|
|APP673 Mutation, isogenic control||Hman iPSC neurons|
|Patient Material, PS1 mutation||Human iPSC neurons|
|Parkinson’s Disease||MPP+ addition||Mouse, human dopa neurons|
|Alpha-Synuclein addition||Mouse, human dopa neurons|
|Patient Material (LRRK2)||Human iPSC dopa neurons|
|Patient Material (A53T)||Human iPSC dopa neurons|
|Pentylene Tetrazole addition||Mouse|
|Developmental Model||Mouse, human iPSC neurons|
|Niemann Pick Type C||NPC1 knockout||Mouse|
|Patient Material and isogenic control||Human iPSC neurons|
|Spinal Muscular Atrophy||Patient Material, isogenic control||Human iPSC motor neurons|
|ALS||Patient Material, healthy control||Human iPSC motor neurons|
|Autism||Patient Material||Human iPSC neurons|
|ADHS||Patient Material||Human iPSC neurons|
You are visiting this page because you desire information about CNS related diseases as CNS degeneration diseases, using in vitro models. We are experts in all steps involved in drug discovery and development. We perform phenotypic screening for drug discovery as part of our modern phenotypic process of drug development.
Please contact us for further questions.