In vitro Disease Models for Screening Services

Functional Phenotypic Screening

Functional and phenotypic screening has enormous importance in CNS drug discovery. NeuroProof offers in vitro disease models that 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 physiological 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 action 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 are 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 Diseases and Mental Disorders

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 neurobehavior diseases as 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 the optimal concentration of the challenge, are the essential parameters for assay optimization.

Subtle stimulations with disease modeling compounds at sub-toxic concentrations mimic early disease pathologies and allow the screening of compounds, which revert the progress of the disease.  Our Abeta assay supports this concept for Alzheimer’s disease and the MPP+ model for Parkinson’s disease.

NeuroProof is your Expert Company for the screening of small molecules, biologicals and 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 is 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 glial 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 long-term expertise in a wide range of co-culture cell systems.

iPSC-Based Models with Patient-Derived Cells for Rare Diseases

One of the most significant advances in cell-based assays has been the development of high-content screening technologies and iPSC-derived neuron cultures disease modeling.

As a collaboration project 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), fragile X syndrome, 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, and 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, and 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 of affected molecular elements of complex signal pathways.

NeuroProof understands that traditional high-content screening, as imaging screening alone, is not the ultimate solution. High-content functional and high-content structural and molecular screening enables 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 such 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 Human iPSC neurons
Parkinson's Disease MPP+ addition Mouse, human dopa neurons
Alpha-Synuclein overexpression AAV Mouse, human dopa neurons
Epilepsy 4-AP addition Mouse
Bicuculline addition Mouse
Pentylene tetrazole addition Mouse
Dravet Syndrome SCN1A AAV knock down, mouse, human
Developmental model Mouse
Pruritus Perturbation model Mouse - sensory neurons
Neuropathic Pain Vincristine model Mouse - sensory neurons
Bipolar disorder Ouabain addition Mouse
Schizophrenia Ketamin addition Mouse
PCP addition Mouse
Developmental model Mouse, human iPSC neurons
Spinal Muscular Atrophy Patient material, isogenic control Human iPSC motor neurons
ALS model Patient material, healthy control Human iPSC motor neurons
Fragile X Syndrome Patient material Human iPSC neurons

 

You are visiting this page because you desire information about CNS-related diseases, such 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.

Contact us for projects

Save
Cookies user preferences
We use cookies to ensure you to get the best experience on our website. If you decline the use of cookies, this website may not function as expected.
Accept all
Decline all
Read more
Analytics
Tools used to analyze the data to measure the effectiveness of a website and to understand how it works.
Google Analytics
_ga
Accept
Decline