Single-Cell Metabolomics for Drug Discovery and Development

Projektinformationen

METADRUG

ID Finanzhilfevereinbarung: 101101077

DOI

10.3030/101101077

Projekt abgeschlossen

EK-Unterschriftsdatum 10 Oktober 2022

Startdatum 1 November 2022

Enddatum 30 April 2024

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany

Periodic Reporting for period 1 - METADRUG (Single-Cell Metabolomics for Drug Discovery and Development)

Berichtszeitraum: 2022-11-01 bis 2024-04-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The project centers on single-cell metabolomics, a groundbreaking technology that unveils the metabolic processes of individual human cells. This level of analysis is crucial because drugs and drug candidates can disrupt cellular metabolism in a cell-specific manner, leading to adverse reactions. Understanding these specific effects is essential for developing safer and more effective pharmaceuticals.

Our previous work, supported by the ERC Consolidator Grant (CoG), resulted in the creation of SpaceM, a pioneering method for single-cell metabolomics. The primary objective of this Proof of Concept (PoC) project is to explore the commercialization potential of SpaceM, specifically its applications in drug discovery. By commercializing this method, we aim to bridge the gap between academic research and practical applications in the pharmaceutical industry, thereby enhancing drug development processes.

Drug discovery and development often face significant challenges due to the cell-specific responses to drug candidates. Traditional metabolomic analysis methods, which typically examine bulk populations of cells, fail to capture the heterogeneity present within these populations. This limitation can lead to incomplete or misleading data, resulting in less effective or unsafe drugs reaching clinical trials and the market. Single-cell metabolomics addresses this gap by enabling the analysis of metabolic processes at the level of individual cells, providing a more accurate understanding of how different cell types respond to drugs.

The overarching objectives of this project include optimizing the SpaceM method for broader use by establishing robust protocols and software tools for single-cell metabolomics. Another key objective is to evaluate its commercialization potential together with pharmaceutical companies. We also aim to protect our intellectual property by filing patents and exploring commercialization pathways through partnerships with innovation incubators.

By achieving these objectives, we expect significant impacts on the pharmaceutical industry. The ability to understand cell-specific drug effects will lead to the development of safer and more effective therapies, minimizing the risk of adverse metabolic reactions. Our efforts will also accelerate innovation by facilitating the translation of scientific discoveries into practical applications, fostering economic growth, and generating intellectual property.

In summary, this ERC PoC project aims to set the stage for the commercialization of SpaceM, a revolutionary single-cell metabolomics method. By refining the technology, establishing industry collaborations, and addressing broader societal implications, we strive to make a significant impact on drug discovery and development, ultimately contributing to the advancement of safer and more effective medical treatments.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

During the project, we focused on refining and optimizing the single-cell metabolomics method, SpaceM, to prepare it for commercial applications. This involved streamlining the technical protocols, processing methods, and software to ensure robustness, scalability, and reproducibility. A key aspect of this work was the development of an approach to evaluate the variability among replicates and individual metabolites at the single-cell level. These advancements were crucial for validating the method's reliability and accuracy.

To demonstrate the method's practical utility, we conducted large-scale experiments. One such experiment involved analyzing cancer cell lines, including HeLa and nine NCI-60 lines, with over 200 samples. Another significant experiment involved CD4+ T cells, where we analyzed over 800 samples, each containing approximately 1000 cells. These experiments showcased SpaceM's capability to handle high-throughput analyses and provided valuable data on the metabolic profiles of different cell types.

We actively engaged with major pharmaceutical companies, including AstraZeneca, GSK, Servier, and Novartis, to present our single-cell metabolomics method. These presentations generated considerable interest, leading to the establishment of collaborations with these companies. Notably, we completed a collaborative viability project with AstraZeneca, evaluating the metabolic responses to a glutaminase inhibitor and another drug of interest. This project provided a proof-of-concept for SpaceM's application in drug discovery, demonstrating its potential to identify cell-specific metabolic effects.

In addition to technical and scientific achievements, we generated new intellectual property related to our single-cell metabolomics method. This intellectual property is in the process of being filed as a patent, which will support our future commercialization activities and protect our innovations.

Overall, the project successfully streamlined the SpaceM method, demonstrated its high-throughput capabilities, and established promising industry collaborations, paving the way for future commercial partnerships and applications in drug discovery.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The primary result of our project was the significant advancement towards the commercialization of the SpaceM method for single-cell metabolomics, originally developed in the ERC CoG project METACELL. This project demonstrated strong interest from major pharmaceutical companies, highlighting the substantial need for such a method in the industry. The successful completion of technical validations and large-scale experiments has shown that SpaceM is at a high Technology Readiness Level (TRL), indicating its readiness for commercialization.

Our results go beyond the current state of the art in several ways. Firstly, SpaceM's ability to analyze metabolic processes at the single-cell level provides a level of detail and precision not achievable with traditional bulk cell metabolomics. This capability is particularly crucial for understanding the heterogeneity within cell populations, which can significantly impact drug efficacy and safety. The successful large-scale experiments with cancer cell lines and CD4+ T cells have demonstrated SpaceM's robustness and scalability, making it a valuable tool for drug discovery and development.