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22.10.2024 17:49
Excellent biomarker for predicting severe stroke outcomes
Dr. Alexander Kollikowski from the Institute for Diagnostic and Interventional Neuroradiology at the University Hospital of Würzburg (UKW) was awarded the Kurt Decker Prize for proof of concept of the earliest local biomarkers in ischemic stroke at the 59th annual meeting of the German Society for Neuroradiology (DGNR).
Würzburg. Ischemic stroke, which accounts for four out of five strokes, requires rapid action to restore blood flow to the brain and prevent permanent brain damage. The blood clot that has cut off blood supply to part of the brain can be removed by catheter-based mechanical thrombectomy, the most effective procedure in acute vascular medicine, to restore physiological blood flow and prevent progression of the infarction. However, even with rapid and efficient treatment, some patients do not benefit sufficiently from this therapy and continue to have neurological deficits even after successful vascular recanalization. While the effectiveness of treatment depends heavily on the timing of the intervention and the extent of tissue damage that has already occurred, certain enzymes, particularly matrix metalloproteinases (MMPs), have also been associated with persistent neurological disorders and bleeding complications, particularly after vascular recanalization.
Kurt Decker Prize for the discovery of a pretherapeutic predictor for severe disease
Dr. Alexander Kollikowski from the Institute for Diagnostic and Interventional Neuroradiology at the University Hospital of Würzburg (UKW) has for the first time investigated the earliest release of these enzymes directly in the brain regions affected by the stroke and their prognostic significance in the therapeutic context before vascular recanalization. For the groundbreaking findings he gained, he received the renowned Kurt Decker Prize at the 59th annual meeting of the German Society for Neuroradiology (DGNR) in Kassel.
About the project, which was financed by the Interdisciplinary Center for Clinical Research (IZKF) Würzburg and the German Research Foundation (DFG) as part of the Clinician Scientist program UNION CVD and the Collaborative Research Center SFB/TR 240 and published in the journal eBioMedicine (The Lancet Discovery Science): Together with Prof. Dr. Michael Schuhmann, head of the clinical laboratory of neurology and the interdisciplinary neurovascular working group, Alexander Kollikowski examined 264 liquid biopsies from 132 stroke patients with large vessel occlusion, which were obtained from the affected vascular segment of the brain before reopening as part of mechanical thrombectomy using a microcatheter procedure. The matrix metalloproteinases could be analyzed in a state before the blood flowing back in after the clot had been removed would have massively changed the situation on site. On the one hand, the researchers found that neutrophils, a type of intravascular white blood cell, migrate into the affected vascular area directly during the stroke and release enzymatically active matrix metalloproteinase-9 (MMP-9), and on the other hand they showed that this process is important for demonstrated the course of the disease.
MMP-9 in liquid biopsies from collateral vessels enables precise prognosis assessment after vascular recanalization
“Our analyzes have shown that local, pretherapeutic concentrations of MMP-9 are an independent predictor of severe cerebral hemorrhage and an unfavorable clinical course including severe disability or death after recanalization,” says Alexander Kollikowski. The results position MMP-9 in collateral vessels as the first local biomarker for identifying high-risk groups among thrombectomy candidates, thereby providing proof of concept for the earliest local biomarkers in ischemic stroke.
What does this mean specifically for therapy? “Determining the release of MMP-9 in liquid biopsies from collateral vessels before vascular recanalization enables precise prognosis assessment for various clinical endpoints after vascular recanalization,” says Kollikowski. “This method could pave the way for tailored treatment strategies for those patients at high risk of adverse outcomes who have not previously been identified and treated early and therefore have significant potential for clinical improvement.”
Validation, point-of-care testing and reverse-translational studies
What’s next? The initial focus is on validating the results in larger cohorts to confirm the robustness and generalizability of the results. In parallel, we will investigate the possibilities of transferring these results into point-of-care testing directly in the angio-surgery during mechanical recanalization as a method for real-time risk assessment. In addition, reverse-translational studies are planned to mechanistically investigate the processes observed in humans in animal models. This approach aims to build a bridge between clinical observations and experimentally addressable pathophysiological processes in order to advance the development of specific, temporally and pathophysiologically coordinated therapy concepts for clinical testing.
Further information:
Press release published on April 22, 2024 on the occasion of the publication of the study.
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