Concept Life Sciences has a strong background in neuroscience and extensive academic links to leading research groups in the field. We help you to understand your MOA and investigate your test compounds across a range of translational models. We share expertise, gathering robust data to drive confident decision making throughout your CNS drug discovery process.
We offer a consultative approach and a suite of customizable assays for investigating CNS (central nervous system) test compounds, including specialist histology readouts as well as ADME & DMPK services and ensuring a comprehensive, tailored CNS program.
Our suite of neuroscience services can be specifically tailored to your project:
- Primary CNS cell-based assays
Ex vivo brain slice assays - RNA and protein-based multiplex histology services
- Brain penetration assessment and receptor occupancy studies
- Neurotoxicity assays
Primary CNS assays
Understanding the effects of your test biologic or small molecule on cells in the CNS is likely a key component of your drug discovery program.
We offer a suite of primary neuronal and glial cell-based assays to help you understand the interaction between your compound or biologic and the nervous system, taking you to clinic faster.
Our highly experienced team can isolate primary CNS cells expressing endogenous targets of interest for use in moderate-throughput phenotypic screening of multiple compounds and MOA studies, helping you achieve accurate, robust results.
Oligodendrocyte precursor cells (OPC)
Understanding how to use Oligodendrocyte Precursor Cells (OPCs) to enhance remyelination in multiple sclerosis is key to bringing new treatments to the clinic. We help you understand the role of your drug candidate on oligodendrocyte behavior and myelination.
OPC Assays
We offer screening using Oligodendrocyte Precursor Cells (OPCs). By assessing the effect of your drug candidate on OPC proliferation, differentiation and apoptosis, we can help you identify compounds with the potential to enhance myelination, bringing you on the best route to the clinic.
We are also developing a high-throughput 3D OPC culture assay and hope to offer human OPC assays in the near future.
We offer screening of primary oligodendrocyte progenitor (NG2+) cells. A promising therapeutic strategy for Multiple Sclerosis is to promote Oligodendrocyte Precursor Cells (OPC) differentiation and maturation into oligodendrocytes (MBP+ cells), repairing myelin degeneration. Understanding the effect of your drug candidate on OPCs to enhance remyelination early in discovery is key to bringing new treatments to clinic.
Understanding the remyelination efficiency of your drug candidate in three dimensions offers a translational link between in vitro cell culture and in vivo investigations, a step up in complexity from our screening assay, and your best route to clinic.
Using our organotypic brain slice assays, we can help you understand the functional effects of your compounds. We can determine the degree of axon (re)myelination by oligodendrocytes, during development or following demyelination, mimicking an MS lesion. We can tailor the assay readouts to your requirements e.g. fluorescent imaging and gene expression analysis by qPCR. To find out more click here.
How our OPC assay works
- Mixed glial cultures are prepared and incubated according to protocol
- OPCs are isolated and cultured with test compounds
- Proliferation and apoptosis/toxicity readouts are assessed after 24 hours and differentiation after 7 days of treatment
- High-resolution immunohistochemistry, combined with semi-automated image analysis techniques, allows accurate quantification of compound effects on OPCs
Organotypic brain slice assays
Understanding the functional response to your CNS drug candidate in a more complex in vitro environment can more efficiently progress your drug discovery program to clinic.
We offer brain slice assays as a low-throughput validation model of your test compound in a complex, multicellular approach. Slice cultures contain and maintain all the relevant neuronal and glial cells, structure and organization of the brain in thick sections of cultured ex vivo tissue providing a powerful translational link between in vitro and in vivo CNS studies in important therapeutic areas such as MS, Parkinson’s and Alzheimer’s disease.
We tailor the assay readouts to suit you. These can include immunohistochemical-based analysis or gene expression studies using qPCR or NGS techniques.
Neurons
Understanding how neurons respond to your drug candidate is key to bringing your central nervous system (CNS) therapies to market.
We offer tailored neuronal assays to better understand the MOA of your therapeutic, de-risking your discovery program.
We can screen neurons as isolated neuronal populations e.g. dopaminergic neurons in Parkinson’s Disease or as more complex mixed cell population assays. We can offer custom assay readouts in addition to the standard viability and survival tests as well as neurite outgrowth.
Using our ex vivo slice culture assay, we can study neuronal behavior in the native environment maintaining intact synapses and circuits. With this approach, we aim to generate high-value mechanistic data that can get you to the clinic faster.
Micoglia
Microglia are an important cellular target in a range of neurodegenerative diseases such as multiple sclerosis and spinal cord injury.
We offer a suite of microglia assays to better understand the MOA of your drug candidate and its potential to enhance the restorative role of activated microglia, de-risking your early discovery program.
We offer monoculture assays using primary cells or cell lines as well as co-culture assays. These assays are ideal for medium-throughput screening and pre-clinical optimization. Working in collaboration with you, we can assess your compound’s ability to dampen the M1 pro-inflammatory response or promote the M2 effector function of activated microglia, identifying molecules that drive repair or enhance resilience of CNS tissue. Depending on the nature of the compound, we can include a combination of both assessments to investigate the M1 to M2 switch.
To progress your drug discovery program further, we offer an ex vivo brain slice model as a translational link between in vitro and in vivo studies.
Our scientific team are experts in glial cell biology and work closely with you to customize your program, supporting your best route to clinic.
Astrocytes
Astrocytes are a particular target cell of interest in the nervous system for developing treatments for brain injuries. As the most abundant type of glial cell (non-neuronal cell) in the brain, astrocytes contribute to homeostasis and provide support and protection for neurons. Astrocytes play a fundamental role in the repair and scarring processes of the brain and spinal cord.
Understanding how astrocytes respond to your drug candidate is key to bringing your treatment to market.
We offer a variety of astrocyte assays to help you study the nuances of astrocyte interaction with your drug candidate. We offer customizable monocultures, co-cultures and ex vivo brain slice assays to understand your compound or target.
Whether you are studying neurodegenerative conditions or neuroinflammation, our expert scientists can guide you to answer your questions around astrocyte polarisation and function, speeding up your drug discovery programs.
Multiple sclerosis and neurodegeneration expertise and in vivo models
We are world-leading experts in the research of multiple sclerosis (MS), a disease that requires understanding of immunology, inflammation and neuroscience. We can provide end-to-end support for MS drug discovery through in vitro OPC (Oligodendrocyte Precursor Cells) assays and our ex vivo slice model, a powerful screening and translational tool as well as lead compound assessment in our in vivo EAE, cuprizone and LPS MS models. Leveraging and combining our neuroscience and immunology expertise, we offer pre-clinical animal models for MS, which focus on the autoimmune and inflammatory component of the disease as well as the myelin damage and repair.
Our experienced Neuroscience team offer specialist discovery services to clients looking to develop novel therapies for a range of neurodegenerative conditions. We can tailor and develop neuroprotective screening assays to discover the mechanism of action of your drug candidate, with customized assays targeting neurons themselves and/or the supportive glial cells in isolation or co-culture. We also provide partnering medicinal and computational chemistry as well as DMPK services to assess brain penetration of your drug candidate.
Cuprizone and LPC models
The cuprizone and lysophosphatidylcholine (LPC) rodent models induce demyelination followed by a recovery period of remyelination. The cuprizone model results in global demyelination whereas the LPC induced model creates a focal lesion.
We can support on the best in vivo model for your question as well as customize the readouts: tailored H&E, specialist multiplex histology and FACS readouts are available. We work closely with you to identify how your novel therapy affects the MS injury or repair process, to build a stronger data package and speed up your route to clinic.
EAE model
Experimental autoimmune encephalomyelitis (EAE) is a T cell-driven disease of the central nervous system in mouse and is considered the gold standard model for brain inflammation and demyelination studies.
Neurotoxicity
We are developing a range of neurotoxicity services, including developmental neurotoxicity assays (DNT), using our pluripotent cell and primary CNS cell-based assay platforms that can support Pharma and non-Pharma clients in their regulatory and safety requirements.