Magda Kordon-Kiszala speaks about the shortcomings of γH2AX at the DDR Inhibitors Summit 2024

Magda Kordon-Kiszala, CEO of intoDNA, addressed an audience of DNA Damage Response (DDR) drug development leaders. Her presentation focused on the key features of STRIDE™ technology, highlighting its potential to become the next-generation standard in analyzing DNA damage across various DDR inhibitors.

BOSTON, UNITED STATES, January 31, 2024 – During the 7th DDR Inhibitors Summit, intoDNA showcased its STRIDE™ technology in a talk titled Unveiling DNA breaks through the direct STRIDEassays for precision in pre-clinical and clinical development of DDR inhibitors. Our fluorescence-based platform directly detects and automatically quantifies DNA breaks or fragments, offering a clear advantage over established, yet non-specific and non-quantifiable methods like gamma-H2AX assays. This article provides a summary of Magda’s presentation, along with the full recording containing examples of customer success stories powered by STRIDE™.

Unveiling DNA Breaks: The Path to Precision in DDR Inhibitor Development

In the evolving landscape of cancer therapeutics, the development of DNA Damage Response (DDR) inhibitors represents a frontier pushing towards more effective and targeted treatments. These inhibitors aim at exploiting the compromised DNA repair mechanisms of cancer cells, inducing a level of DNA damage that surpasses the cell’s repair capacity, thus leading to cell death. However, the journey from concept to clinic is paved with challenges, primarily in accurately measuring DNA damage to gauge the efficacy of these inhibitors.

The Limitations of γH2AX

Traditionally, γH2AX has been the gold standard biomarker for assessing DNA double-strand breaks, serving as an indirect indicator of DNA damage. However, reliance on such biomarkers comes with limitations. γH2AX, for instance, may indicate DNA stress responses unrelated to actual DNA breaks, such as cellular stress or structural DNA distortions. Additionally, technical challenges such as non-specific antibody binding and the subjective quantification of DNA damage further complicate its reliability. Learn more about how STRIDE™ and γH2AX compare.

We should only accept the directly detected DNA breaks as a unifying pharmacodynamic readout in the DDR inhibitors context.

says Magda Kordon-Kiszala, CEO at intoDNA.

STRIDE: A Leap Forward in DNA Damage Measurement

In response to these challenges, intoDNA introduces STRIDE (Sensitive Recognition of Individual DNA Ends), a revolutionary platform for direct, specific, and sensitive detection and labelling of DNA breaks. This fluorescence-based technology surpasses traditional methods by offering direct detection of DNA breaks within any biological material, without the need for DNA isolation. Its high signal-to-noise ratio allows for objective quantification of DNA damage at the individual lesion level, which is facilitated by in-house developed AI algorithms.

Applications and Advancements

STRIDEnot only demonstrates superior specificity and sensitivity but also boasts compatibility across various stages of drug development. It offers a range of solutions, including specific assays for detecting double-strand breaks (dSTRIDE) and single-strand breaks (sSTRIDE), alongside customized assays tailored to measure the activity of specific DNA repair pathways.

Through various preclinical and clinical applications, STRIDEhas shown promising results. It has revealed mechanisms of action and target engagement that were not possible to be assessed by standard methods based on the detection of DNA repair markers. For instance, in preclinical models where other assays failed, STRIDEwas able to detect single-stranded breaks and DNA fragments, providing insights into the efficacy of DDR inhibitors. 

Collaborative Success and Future Directions

In collaboration with leading institutions and pharmaceutical companies, intoDNA’s STRIDEassays have been applied to a wide range of studies, from assessing the mode of action of novel inhibitors to quantifying DNA breaks in tumor biopsies. These collaborations have yielded valuable data, offering new perspectives on the role of DNA damage in cancer therapy and the potential of DDR inhibitors.

As we move forward, the STRIDEplatform continues to respond to the pursuit of innovation in the field of precision medicine. It not only enhances our understanding of DNA damage and repair mechanisms but also opens new avenues for developing more effective cancer treatments.

A Call to Action

IntoDNA’s journey with STRIDEis just beginning. We invite researchers, clinicians, and pharmaceutical companies to explore the potential of this platform to advance the development of DDR inhibitors. Together, we can turn the tide against cancer, armed with precise tools and a deeper understanding of the DNA damage response.

For more information or to discuss potential collaborations, please reach out to intoDNA. Let’s stride towards a future where cancer therapy is not just a one-size-fits-all solution but a tailored, precision-driven approach that saves lives.