Metrion launches new Nav1.9 assays to elevate pain drug discovery

Ion channels are a major class of drug targets for modulating pain transmission and controlling chronic pain. The voltage-gated sodium channel, Na_V1.9, has been identified as a critical component of pain signalling. While Na_V1.9 holds great promise as a non-opioid pain target, the discovery and development of new chemical entities has been hampered by the availability of robust cellular reagents suitable for high-throughput electrophysiology.

Metrion has addressed this challenge with the development of robust stably expressing Na_V1.9 cell lines (human and rat) which have been validated on our high-throughput automated electrophysiology systems (QPatch 48 and Qube 384).

Our unique approach to Na_V1.9 drug discovery

Alongside our highly experienced electrophysiologists, Metrion’s Na_V1.9 drug discovery assays, in combination with other pain research related services, combines the following to support our customer’s’ discovery needs:

• Leadership team with over 100 years’ experience in drug discovery research
• High-throughput hit finding using a robust human Na_V9 cell line
• Assays suitable to support hit-to-lead and lead optimisation
• Rat Na_V1.9 assay for species confirmation
• Complete panel of sodium channels for selectivity profiling including other pain targets such as Na_V1.7 and Na_V1.8
• Large collection of off-target counter screens including CiPA panel for cardiac safety risk assessment
• Access to mechanistic and translational assays using the manual patch clamp technique with rat DRG neurons

Figure 1. Example Na_V1.9 screening cascade – Metrion’s unique approach to Na_V1.9 drug discovery.

Understanding Na_V1.9: A critical pain target

Role of Na_V1.9 in sensory neurons

Na_V1.9 is a voltage-gated sodium channel predominantly expressed in peripheral sensory neurons, where it plays a vital role in pain signalling. These channels contribute to the excitability of nociceptive neurons directly influencing pain pathways. The unique biophysical properties of Na_V1.9 plays a key role in regulating the threshold for neuronal firing and is seen as an attractive target for non-opioid pain management.

Genetic mutations and pain disorders

Na_V1.9 has been linked to various pain disorders through genetic mutations leading to both chronic pain syndromes and insensitivity to pain. These discoveries further support the significance of Na_V1.9 in pain physiology and the importance of this particular sodium channel subtype as a pain target.

Need for reliable screening assays: Overcoming challenges in studying Na_V1.9

Despite its importance in pain research, Na_V1.9 remains one of the most difficult sodium channel targets to prosecute due to:

• Functional expression challenges: Difficulty in expressing Na_V1.9 in stable heterologous systems
• Unique biophysical properties: Activation and inactivation kinetics of Na_V1.9 require voltage-control only offered by patch clamp techniques, including automated electrophysiological systems

Metrion has overcome these challenges by developing robust Na_V1.9 cell lines which have been validated using the QPatch 48 and Qube 384 providing high quality reproducible data.

These enhancements place Metrion at the forefront of Na_V1.9 drug discovery.

Figure 2. Example family of current recordings of hNa_V1.9 using the Qube automated electrophysiology platform (A). Current-voltage relationship of hNa_V1.9 (B).

Advantages of automated patch clamp technology in Na_V1.9 screening

Leading the way in Na_V1.9 hit finding, Metrion has exceptional expertise in automated electrophysiology platforms, which delivers:

• Greater throughput: The ability to screen thousands of compounds in a fraction of the time
• Improved data consistency: Reduced variability and enhance reproducibility
• Reduced timelines: Lower resource requirements with faster turnaround providing a more cost-effective programme

Why researchers should choose Metrion to support their Na_V1.9 programmes

Uniquely positioned as a leader in ion channel drug discovery, Metrion scientists have extensive experience in neuroscience, in particular pain, gained from both academic and industry environments. By partnering with Metrion, customers benefit from:

• Industry-leading expertise: A team of highly skilled scientists with extensive knowledge of ion channel pharmacology
• State-of-the-art technology: Access to automated patch clamp systems for high-throughput screening
• Gold standard electrophysiology: Experts in all in vitro manual patch clamp configurations
• Extensive collection of ion channel cell lines: Access to broad range of ion channel targets for selectivity assessment, including CiPA panel
• Customised research solutions: Tailored services designed to meet specific project needs in both in vitro and translational assays
• Fast and reliable data reporting: Accelerating the pace of drug discovery with rapid turnaround times
• Translational assays: Validation of lead compounds in sensory neurons
• Comprehensive scientific support: Providing detailed data interpretation and expert guidance

Metrion’s commitment to excellence in ion channel screening

Metrion continues to lead the way in ion channel research, and the launch of its Na_V1.9 capabilities represent a significant advancement in pain drug discovery. By addressing key challenges associated with Na_V1.9, the use of cutting-edge automated patch clamp technology and rodent translational models, Metrion is ready to support your projects to identify new pain therapies.

For scientists looking to accelerate their drug discovery efforts, Metrion provides the expertise, technology, and support necessary to achieve breakthrough discoveries. As the demand for non-opioid pain therapeutics grows, Metrion’s commitment to innovation will continue to drive progress in this crucial field.

Apply Metrion’s expertise to your Na_V1.9 research

Contact us today to learn how Metrion’s cutting-edge pain research services can help you achieve your research goals: