STEMOD™ Advanced Drug Discovery Service

Overview of CNS Drug Discovery

CNS drug discovery has been hampered by inadequate understanding or consideration of a number of factors. These include the complexity of brain anatomy and function; the neuro-PK with regard to the blood-brain barrier (BBB) transport and intra-brain distribution as well as the measures to study these processes; adequate biomarkers of CNS drug effects (neuro-PD), and the complex nature of CNS diseases. Also, the reductionist view and thereby lack of understanding of the interaction and interdependencies of all these factors have contributed to the high attrition rates of CNS drugs.

Process of CNS drug discovery

One-stop CNS Drug Discovery Services at Creative Biolabs

Creative Biolabs has extensive experience in drug discovery and has successfully accomplished hundreds of projects. We have developed a comprehensive technology platform to provide one-stop CNS drugs discovery services. Our platform has advanced neuroscience ex vivo models, neuroscience assay technique, and neuroscience research tools. These technologies will cover every important stage of CNS drug discovery, resulting in a one-stop shop for our customers.

Technology Platform

If you are looking for assistance on CNS discovery services, or you are interested in other neuroscience services, please feel free to contact us for more information.

Our services are exclusively for research use, providing the tools and expertise needed to explore the vast potential of CNS therapeutics.

• Utilize advanced bioinformatics and genomic tools to identify viable therapeutic targets within the CNS
• Design and optimize assays that accurately reflect CNS conditions to study receptor interactions and signaling pathways
• Implement robust HTS systems to evaluate thousands of compounds against CNS targets, identifying lead candidates for further development
• Leverage structural biology techniques, including X-ray crystallography and NMR, to design and optimize small molecules
• Conduct behavioral studies in animal models to assess the efficacy of candidate compounds in neurological and psychiatric conditions
• Evaluate the pharmacokinetic profiles and toxicity of compounds via tailored studies to anticipate how they will behave in humans and identify any potential safety concerns
• Explore novel drug delivery systems utilizing nanotechnology to enhance the bioavailability and targeted delivery of CNS therapeutics
• Develop formulations suited for the unique requirements of CNS drugs, including those requiring blood-brain barrier penetration

We also offer flexibility in our services, including but not limited to:

Published Data

iPSC-based drug discovery is a promising technique for developing novel treatments for neurodegenerative diseases, such as ALS, that lack useful disease models. Three candidate anti-ALS drugs were identified in an iPSC-based drug screen and are currently being evaluated for safety and efficacy in clinical trials.

Motor neurons (MN) differentiated from iPSCs of FALS patients carrying missense mutations in the FUS and TDP-43 genes recapitulate several neurodegenerative phenotypes. A drug screening analysis conducted at Keio University screened 1232 compounds from an existing drug library using a 96-well plate and a high-content screening system to explore drugs that inhibit ALS-related phenotypes. The first screen was performed using MNs derived from FALS patients with FUS mutations, and 95 out of 1232 drugs were identified. Subsequently, a second screen was performed using MN from FALS patients with TDP-43 mutations and identified nine drugs that inhibited ALS-related phenotypes.

Fig. 1 iPSC-based modeling of ALS motor neuron phenotypes and drug screening using an FDA-approved drug library.¹

Applications

The service is designed to facilitate the development of CNS drugs, addressing several key challenges faced in CNS research. Here are the main applications of this service:

• Research and Innovation: STEMOD™ is particularly geared towards research use only, enabling researchers to explore innovative solutions in CNS drug discovery.
• One-stop Solution: With a comprehensive technology platform, it serves as a one-stop shop for all CNS drug discovery needs, streamlining the research process from initial drug screening to the final assessments.
• High Attrition Rate Solution: By addressing the common pitfalls in CNS drug discovery, this service aims to reduce the high attrition rates seen with CNS drugs.

By utilizing this service, companies and research institutions can benefit from advanced modeling, screening technologies, and detailed research tools essential for successful drug innovation in neuroscience.

FAQs

Q: What types of assays can be integrated with the STEMOD™ platform for drug testing?

A: The service supports a variety of assays, including high-throughput screening, electrophysiological measurements, toxicity profiling, and functional assays like viability, differentiation, and proliferation tests. We can also implement 3D imaging and organ-specific functional assessments to monitor the effects of candidate drugs on the organoid models in real time, offering a comprehensive view of drug behavior.

Q: What is the typical timeline for drug discovery projects using the platform?

A: The timeline for a drug discovery project using the platform varies depending on the complexity of the study and the customization required. Typically, generating patient-derived organoids can take a few weeks, followed by drug screening, which might last anywhere from several weeks to a few months. We work closely with clients to outline specific project timelines based on their goals and the technical requirements involved.

Q: How do you ensure the reproducibility and scalability of your organoid models?

A: Reproducibility and scalability are core aspects of our platform. We utilize standardized protocols for the differentiation and culture of hPSC-derived organoids, ensuring that each model meets consistent quality criteria. Our organoid culture systems are designed to be scalable, allowing for high-throughput drug screening if needed. Regular quality control assessments are also performed to monitor the functionality and stability of the organoids over time.

Q: What kind of support do you provide during the drug discovery process?

A: We provide end-to-end support throughout the entire drug discovery process. From initial consultation to project planning, model customization, assay development, and data analysis, our team of scientists works closely with clients to ensure that their specific needs are met. We also offer detailed reporting, troubleshooting assistance, and follow-up discussions to refine experimental design or interpret results.

Scientific Resources

Repurposing of Existing Drugs for CNS Disorders

Reference

1. Okano, Hideyuki, et al. "Ropinirole, a new ALS drug candidate developed using iPSCs." Trends in pharmacological sciences 41.2 (2020): 99-109.

For Research Use Only. Not For Clinical Use.