Circular RNA blood biomarker identified in EMBARC study and validated in naturalistic clinical study distinguishes future responders and non-responders to SSRIs
Biomarker potential may extend to disease monitoring and prediction of remission
Albuquerque, N.M., May 07, 2024 - Circular Genomics, the global leader in circular RNA biomarkers for precision psychiatry and neurology, today announced study results published as a preprint on bioRXiv demonstrating the potential for Circular Genomics’ first blood assay to predict patient response to sertraline as well as capacity for SSRI class prediction overall. The assay is based on the identification of a brain-enriched circular RNA (circRNA) blood biomarker that can predict response to the SSRI class of antidepressants.
“The results seen in the EMBARC study reinforce the predictive power of this brain-enriched circRNA and its ability to distinguish patients most likely to respond to SSRIs using a robust blood-based biomarker,” said Paul Sargeant, PhD, CEO of Circular Genomics. “Current depression treatment protocols employ a ‘trial and error’ approach to finding the right treatment. We aim to streamline this process by providing accurate personalized treatment guidance to help patients suffering with depression. We look forward to introducing the first circRNA-based assay for prediction of response to antidepressant treatment later this year.”
The results stem from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a large antidepressant response study led by Dr. Madhukar Trivedi from UT Southwestern Medical Center. The paper, titled “A brain-enriched circRNA blood biomarker can predict response to SSRI antidepressants,” describes the use of samples from the EMBARC study to evaluate differential expression of a brain-enriched circRNA as a biomarker for directly predicting response to SSRI treatment. Key findings include:
Identification and validation of circRNA biomarker: Close to 80% higher baseline (before treatment) blood levels of circRNAx in patients that did not respond to sertraline compared to those that did respond; these results are replicable across a separate EMBARC sample cohort. CircRNAx levels at baseline in blood cells of a naturalistic clinical study predict depression remission following treatment with SSRIs.
Specific to SSRI response: Specificity of circRNAx in predicting SSRI response with no differential expression related to response to placebo or remission following bupropion treatment after failure to respond to sertraline.
Biomarker for ongoing monitoring: Statistically significant increases of circRNAx levels after 8 weeks of sertraline treatment are observed in responders to sertraline who later achieved remission, indicating that circRNAx is responsive to treatment and displays a dynamic expression profile that can be used for disease monitoring and prediction of long-term recovery.
Linkage to known mechanisms of antidepressant response: Expression of circRNAx within the brain is specifically regulated by molecular cascades with relevance to SSRI antidepressant response, such the Serotonin and Brain-Derived Neurotrophic Factor receptor signaling.
“Our data provide evidence that blood levels of a brain-enriched circRNA associated with known mechanisms of antidepressant response can accurately predict response to SSRIs and remission in patients with major depressive disorder,” said Nikolaos Mellios, MD, PhD, co-founder and CSO of Circular Genomics. “These findings reinforce our belief that the expression of specific circRNAs in the blood can act as an indirect ‘window into the brain’ and provide actionable insights for the better diagnosis and treatment of brain disorders.”
Circular Genomics plans to launch the company’s first test later this year, which will predict response to SSRI antidepressants and address the issue of high therapy failure rates and low clinical outcomes. Discover more about Circular Genomics and its pioneering technology at https://circulargenomics.com.
About circular RNA
Circular RNAs (circRNAs) are highly stable non-coding RNAs that are particularly abundant in the brain. circRNAs have been shown to be important for brain development, maturation, function, and aging and have been linked to many psychiatric and neurological disorders. They are highly sensitive to changes in neuronal activity or activation of various neuronal receptors and cross the blood-brain-barrier, so are readily detectable in the blood. Due to the above characteristics, circRNAs hold significant potential to become ideal molecular biomarkers for better diagnosis and treatment of psychiatric disorders.
About Circular Genomics
Circular Genomics is the world-leading developer of circular RNA-based precision medicine tools, data and diagnostics for psychiatry and neurology. Leveraging exclusive licenses and pioneering technologies in circular RNA, we are reshaping the standard of care for major depressive disorder and other neurological diseases. Initial products include assays to assess and tailor optimal treatment protocols for individual patients, validating treatment effectiveness within days to weeks rather than months. For additional details, please visit www.circulargenomics.com.
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