Circular Genomics Unveils Accurate circRNA Test for SSRI Antidepressant Response

Circular Genomics, a leader in circular RNA biomarkers for precision psychiatry and neurology, has revealed promising results from their latest research. The findings, published as a preprint on bioRXiv, highlight the potential of Circular Genomics' blood assay to predict patient responses to sertraline, a common SSRI antidepressant, as well as to the SSRI class overall. This innovative assay is designed around the identification of a brain-enriched circular RNA (circRNA) biomarker detectable in the blood.

Paul Sargeant, PhD, CEO of Circular Genomics, emphasized the significance of these findings, noting that the current approach to depression treatment often involves a "trial and error" method to identify effective medications. The new circRNA-based assay aims to streamline this process by offering precise, personalized treatment recommendations, potentially transforming mental healthcare by introducing precision medicine.

The results are derived from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a comprehensive research project led by Dr. Madhukar Trivedi of UT Southwestern Medical Center. The study paper, titled "A brain-enriched circRNA blood biomarker can predict response to SSRI antidepressants," used samples from the EMBARC study to evaluate the expression of this specific circRNA biomarker in predicting SSRI treatment outcomes. Key findings from the study include:

1. Biomarker Identification and Validation: The study found that patients who did not respond to sertraline had nearly 80% higher baseline blood levels of the circRNA biomarker compared to those who did respond. These findings were consistent across different sample cohorts from the EMBARC study.

2. Specificity to SSRI Response: The circRNA biomarker was specific in predicting responses to SSRI treatment, with no significant expression changes observed in patients responding to placebo or to bupropion after failing sertraline treatment.

3. Utility in Ongoing Monitoring: The biomarker levels increased significantly after eight weeks of sertraline treatment in responders who later achieved remission, suggesting its potential for monitoring disease progression and predicting long-term recovery.

4. Link to Antidepressant Response Mechanisms: The circRNA biomarker's expression in the brain is regulated by molecular pathways relevant to SSRI response, such as Serotonin and Brain-Derived Neurotrophic Factor receptor signaling.

Dr. Nikolaos Mellios, co-founder and CSO of Circular Genomics, underscored the importance of these results, highlighting that blood levels of the brain-enriched circRNA correlated with known antidepressant response mechanisms can predict SSRI response and remission in patients with major depressive disorder. He suggested that specific circRNAs in the blood could provide valuable insights for diagnosing and treating brain disorders.

Circular Genomics plans to introduce their first test later this year, aimed at predicting responses to SSRI antidepressants and addressing the high failure rates and low clinical outcomes currently seen in depression treatment.

Circular RNAs (circRNAs) are stable non-coding RNAs abundant in the brain, playing crucial roles in brain development, function, and aging. Their sensitivity to neuronal activity and ability to cross the blood-brain barrier make them suitable candidates for molecular biomarkers in psychiatric and neurological disorders.

Circular Genomics is pioneering the development of precision medicine tools using circular RNA technology to enhance the diagnosis and treatment of psychiatric and neurological conditions. These innovations promise to improve treatment protocols and validate their effectiveness more quickly, potentially bringing significant advancements to mental healthcare.

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