Neuroscience

Advancing Neuroscience Drug Discovery for Neurological and Psychiatric Conditions

Neuroscience drug discovery encompasses neurodegenerative diseases and neuropathic pain, plus psychiatric conditions such as schizophrenia and substance use disorders.

Neuroscience holds the key to unlocking treatments for neurodegenerative diseases, neuropathic pain, schizophrenia, substance use disorders, and more. Despite the complexities of developing CNS drugs, Sygnature Discovery’s expert team maximizes success through validated in-vivo models, high-quality molecules, and disease understanding. While many large pharma companies have scaled back their research in the field over the last decade, there remains a clear unmet medical need, with significant investment in neuroscience drug discovery continuing across the broader healthcare sector.

Sygnature Discovery’s scientists offer an integrated neuroscience platform to support client projects in this particularly challenging therapeutic area. With profound expertise, we engineer customised strategies for small molecule discovery, targeting vital classes central to neuroscience therapeutics, such as enzymes and GPCRs. Complementing this, our well-established capabilities in CNS-focused medicinal chemistry and DMPK are bolstered by a diverse array of bioscience assay platforms and advanced technologies. In the realm of in vivo studies, Sygnature’s neuroscientists possess extensive expertise, cultivated and refined over years of dedicated practice. Covering the full spectrum of neuroscience, our techniques encompass microdialysis, receptor binding studies, and behavioural studies. In an evolving landscape, Sygnature is at the forefront of transformative neuroscience research.

Cutting-Edge In Vitro Assay Platform for Neuroscience Drug Discovery

Our state-of-the-art in vitro assay platform is tailored for advancing neuroscience drug discovery, offering:

1. High-Content and Live Cell Imaging Platforms: These platforms provide robust support for a diverse range of central nervous system (CNS) focused assays, generating comprehensive multi-parametric data from relevant cell types.
2. Customisable Excitotoxicity and other Bespoke Assays: Identify potential neuroprotective agents with ease through our adaptable excitotoxicity assays, facilitating the discovery of compounds that safeguard against neuronal damage. Our bespoke assays enable meticulous study and quantification of neurite dynamics and structure, providing invaluable insights into neural development and function.
3. Microglia-Based Neuro-Inflammation Support: Our microglia-based assays contribute to neuro-inflammation research by assessing critical factors such as phagocytosis, M1/M2 polarization, and cytokine production.
4. Mitochondrial Function: Efficient mitochondrial function is crucial for neurotransmission, cognitive functions, emotional regulation, and the overall preservation and adaptation of neuronal networks. Understanding the role of mitochondria in these processes is essential for exploring potential therapeutic strategies for age-related cognitive decline and neurodegenerative disorders. At Sygnature Discovery, we explore a plethora of assays and endpoints that are necessary to understand mitochondrial function and health.
5. Phenotypic Screening for Novel Compounds: Employing medium-throughput screens (MTS) encompassing up to 20,000 compounds in high-content assays, our phenotypic screening aids in pinpointing innovative chemical starting points, and enhancing drug discovery efforts.
6. Comprehensive mRNA and Protein Expression Analysis: Gain insights into intracellular signalling pathways through meticulous analysis of mRNA and protein expression, elucidating key molecular mechanisms.
7. Expertise in Culturing CNS Cell Types: Our adeptness extends to cultivating both immortalised and primary rodent neuronal and microglial cell types, ensuring accurate modelling of the CNS environment.
8. Human Disease iPSC-Derived Cells: By utilising human disease-induced pluripotent stem cell (iPSC)-derived neurons and microglial cells, our research brings us closer to mimicking the human disease state, enhancing the relevance of our findings.
9. Innovative Computational Chemistry Approach: Our computational chemistry group has successfully implemented and validated our unique MPO approach, optimising the design of brain-penetrant drugs for enhanced efficacy.
10. Guidance from DMPK Experts: The DMPK group offers expert advice on relevant assays and tissue distribution studies, enabling a comprehensive assessment of a drug’s potential for exposure and target engagement within the CNS.

Advancing In Vivo Models for Comprehensive Evaluation

Our biological sciences department provides tailored in vivo models for assessing CNS pharmacodynamics and efficacy endpoints across a wide range of neurological and psychiatric indications. This includes disorders such as substance use disorders, schizophrenia, binge eating disorder, and Parkinson’s Disease. Our specialised models facilitate a deeper understanding of the effects and potential treatments for these complex conditions.