Enter the New Era of CNS Drug Discovery

It's time to try a different approach.

CNS drug discovery isn't for the faint of heart. We can't be deterred by clinical failures, but it's clear that some approaches aren't working. It's time to start over, building upon the foundations of our current research. It's time to explore new tools and techniques, gathering the data that drives confident decisions in the earliest stages of development. It's time to break through with discovery of new, long-awaited therapies. Collaboration is key, as we pool knowledge and share experience that will allow us all to reach our goals.

What can we accomplish together?

Meet the Scientist

Sarah Almond, MSc, Associate Director of Biology

Having once sat on the other side of the bench as a Charles River client, Associate Director of Integrated Biology Sarah Almond is intimately familiar with the pressures facing today’s drug seekers. Her experience working for a couple of Cambridge-area companies informs her approach to finding creative solutions to their toughest challenges. In her current role, she splits her time between managing the daily operations of integrated discovery programs across Charles River’s CNS sites, and building new client partnerships. She has a keen interest in further expanding her department’s existing proteomics capabilities and in showing clients how to move their CNS research efficiently from in vitro to in vivo studies. Professionally, Sarah Almond leads the company’s involvement with the Psychiatry Consortium, a joint initiative with the Medicines Catapult and the Dementia Consortium that brings together academia, industry, charity, and government-funded organizations to bring forward novel targets for the treatment of CNS disorders

Translating Neurological Stem Cell Research Into Therapies for Today's Patients

Wednesday, May 6 | 9:00 a.m. - 5:00 p.m.

AC Hotel by Marriott | South San Francisco, CA 94080

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Disease Areas

Services

Early Discovery

Medicinal Chemistry

Modern medicinal chemistry is highly multidisciplinary, driving CNS drug discovery innovation from novel synthesis and delivery to screening. Small molecule and large molecule CNS targets range from GPCRs to kinase inhibitors and have proven useful for studying diseases of neurodegeneration such as Parkinson’s disease and Huntington’s disease.

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Antisense Oligonucleotide (ASO) Screening

ASO screens can be designed to evaluate a variety of proven mechanism of action approaches for antisense oligonucleotide therapy. To date, we’ve developed ASO screening assays primarily for rare neurodegenerative disorders.

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High-Throughput Screening

Utilizing vast compound libraries, chemists use high-throughput screening to rapidly identify promising compounds for neuroscience target validation and identification.

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High Content Imaging

In CNS research, we use high content imaging to characterize stem cell-derived neuronal lineages and a host of validated assays like apoptosis, autophagy, protein aggregation, cell or mitochondrial motility and migration, epigenetic modifications, maker expression, protein acetylation and phosphorylation, receptor internalization and degradation, sub-cellular localization and translocation of transcription factors.

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Proteomics

Neurological disease research and drug discovery uses proteomics to search for disease or pharmacological signatures. This allows us to understand biological mechanisms and identify specific proteins and their modifications, e.g., ubiquitination or phosphorylation in Parkinson’s disease and Huntington’s disease models.

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CRISPR Gene Editing

CRISPR Cas9 gene editing has transformed drug discovery and development. It has been used successfully for editing the Huntington CAG repeat in human iPSCs and for high-content screening of disease-relevant in vitro assays for ALS.

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Human iPSCs

Generating induced pluripotent stem cells (IPSCs) for neurological disease-relevant assays, coupled with specific differentiation protocols for production of neurons and/or astrocytes, improves translation to in vivo models.

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Ion Channel Profiling

Our ion channel assays guide your early screening investigations and selectivity profiling with 120 targets organized in functionally-validated disease areas. CNS-focused Channel Panels™ include pain, psychiatric disorders, neurodegeneration, and seizure disorders.

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Research Models and Services

CRISPR Mice and Rats

Using CRISPR/Cas9 genome editing to create unique rat and mouse models of neurological disease offers the advantages of time savings, reduction in animal use, and improved overall cost-effectiveness.

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RNAi Mouse Models

Where small molecule drug therapy has failed, RNA interference has emerged to silence specific genes such as those identified for genetic neurodegenerative disorders like spinocerebellar ataxia and Huntington’s disease.

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Neurological Surgical Procedures

Our skilled veterinary surgeons and technicians perform a comprehensive selection of procedures for rats, mice, guinea pigs, and large animals, including bilateral brain cannulation, microdialysis probe implantation, spinal nerve ligation, 6-OHDA Parkinson’s disease lesion models, and more.

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Research Models

You can reduce attrition rates with animal models that closely mimic neurological diseases. We can support your neuroscience research with a range of standard and custom in vivo pharmacology models for Alzheimer’s, Parkinson’s, psychiatric disorders, pain, brain injuries, and more.

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Microbiome & Next Generation Sequencing

In recent years, the connection between the gut microbiome on host physiology and the onset of neurological disease has become recognized as an important area of interest. Next generation sequencing can assess the biodiversity of your animal colony and research experiments.

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CRADL

The Charles River Accelerator and Development Lab (CRADL™) offers turnkey vivarium rental space for both emerging and well-established biotech companies. Two locations, CRADL™ East in Cambridge, MA and CRADL™ West in South San Francisco, CA, serve researchers on both coasts of the United States.

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CNS Tools

Electrophysiology

Assessing the functional activity of your neuronal cell cultures, brain slices, or tissue can be cumbersome. Whatever your therapeutic area – neuromuscular, schizophrenia, neuropathic pain, or epilepsy – we have the equipment and expertise to conduct automated patch-clamp electrophysiology and multi-electrode array studies.

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Neurological Imaging

Neurological small animal imaging methodologies have the potential to dramatically increase the efficiency of lead candidate selection by providing earlier and more highly predictive data. See what state-of-the-art noninvasive preclinical imaging like pharmacological MRI, nuclear, and functional ultrasound imaging can add to your program.

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Behavioral Testing

Measuring behavioral changes is widely used for neurological diseases associated with cognition, psychiatric disorders, and neurodegeneration. This method is especially powerful when performed together with in vivo assays that assess neurochemical changes in the same animal.

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Microdialysis

Microdialysisis a noninvasive method for collecting CSF and other fluid samples from the brain or tissues of awake animals. Samples are typically analyzed using LC-MS to assess neurochemical metabolites, therapeutic efficacy windows, or fluid biomarkers.  

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Fine Motor Kinematic Analysis

Impairment of motor skills is used as an early diagnosis marker in neuromuscular and neurodegenerative diseases. To test therapeutic compounds in animal models, characterizing fine motor impairment can reveal early changes in disease models and provide an opportunity to pharmacologically manipulate.

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Touchscreen Testing

Cognitive changes are challenging to measure in animal models. Touchscreen testing measures mouse behavior by recording a mouse’s actions and screen touch responses to images and locations on a computer screen.

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Neurochemistry

We can study neurotransmitters and metabolites from many different types of biological matrices using a variety of bioanalytical tools such as LC-MS, electrochemical detection, or fluorescence detection.

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Safety Pharmacology

Abuse and Dependence Liability Testing

Any new chemical entity that penetrates or targets sites in the central nervous system requires an assessment for abuse and liability. Our specialized neurobehavioral testing strategies can help you assess CNS-mediated effects in compliance with both international health and drug control guidelines.

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Neuropathology

Services in neuropathology range from whole-body perfusions to specialized staining capabilities. Our skilled team of pathologists regularly assists with study design, development strategies, and regulatory submissions for a wide variety of compounds affecting the nervous system.

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Neurotoxicity Testing

Testing your therapy for adverse effects on the chemistry, structure, or function of the nervous system is critical. Our neurotoxicology program is dedicated to a broad range of products from biologics to small and large molecules in both rodent and nonrodent species.

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Safety Pharmacology Studies

We incorporate both in vitro and in vivo models and assays into our toxicology and safety pharmacology studies. These range from in vitro electrophysiology assays that assess potential risks for specific neurodegenerative and neuroinflammatory diseases such as Huntington’s disease or neuropathic pain, to the design of FOB/Irwin screening in animal models.  

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Bioanalysis

From CNS early discovery through clinical sample analysis, we continually develop and validate comprehensive bioanalysis (via mass spectrometry, immunohistochemistry, cell-based assays, flow cytometry, molecular biology, PK/PD, and biomarker) assays to meet the ever-changing demand of innovative drugs through the pipeline.

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Biomarkers

Predictive biomarkers are critical tools in CNS drug discovery and development, as they assess activity of candidate therapeutics and validate targets to provide mechanism of action, therapeutic efficacy, and toxicity.

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Scientific Resources

CNS Drug Discovery Facilities

Charles River is proud to advance the field of neuroscience with sites and staff dedicated to your CNS research. When you’re ready to transition from the discovery phase into development, our global network of facilities and comprehensive portfolio deliver the service and support to take your therapy to the clinic and beyond.

Kuopio, Finland

Take a look inside the European base for our Neuroscience Center of Excellence in Kuopio, Finland, accelerating CNS drug discovery with deep science and the most advanced technologies, models, and study methods.

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South San Francisco, CA

Explore our West Coast US location with Arash Rassoulpour, Senior Director of Discovery, as he explains the site’s origins, evolution as a premium center for tools and technologies to support cutting-edge CNS research.

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Your Team

Meet your collaborators: Charles River's Neuroscience Scientific and Commercial Leadership Team.

Antti Nurmi

Antti Nurmi, PhD, MSc

Managing Director, Discovery Services
Kuopio, Finland

"Tackling neurodegenerative disorders requires a more in-depth understanding of the mechanisms behind the diseases. Drug developers are partnering with leading service providers to explore new routes. We are implementing clinically relevant structural and functional imaging in animal models to support translational drug research for CNS disorders."

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Arash Rassoulpour

Arash Rassoulpour, PhD

Senior Director, Site Operations
South San Francisco, CA

“We’re taking advantage of the past to inform our present and future; with every project and every partner, we’re using our collective experience and learning to ask more relevant questions. By analyzing the causes for early failures, we can identify and develop more predictive assays that effectively improve clinical outcomes and minimize attrition.”

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Gunnar Flik

Gunnar Flik, PhD

Site Director, Operations
Groningen, The Netherlands

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David Fischer

David Fischer, PhD

Executive Director,
Scientific Advisory Services
Saffron Waldon, UK

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Brian Roche

Toni Ahtoniemi, PhD

Associate Director, Client Services
Kuopio, Finland

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Velu Karicheti

Carina Peritore, PhD

Product Manager, Neuroscience Discovery,
Wilmington, MA

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