NfL and EGFL7 as biomarkers for neuroaxonal damage and BBB-integrity in neuroinflammation: A translational approach (B14*)

• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213904703

We hypothesize that marker for BBB-integrity (EGFL7) and neuroaxonal damage (NfL) underlie specific pathophysiologic aspects of Multiple Sclerosis (MS) pathology and that their combination helps to improve monitoring of pathological processes within the CNS and prognostic potential in patients with MS. Therefore we first of all plan to experimentally validate EGFL7 and NfL as markers for BBB-integrity and neuroaxonal damage by taking advantage of human and murine in vitro cultures under different conditions and experimental models of acute (focal inflammatory lesion, relapsing-remitting EAE, stroke) and chronic neuronal injury (chronic EAE models). In a second step we plan to unravel the influence of lesion localization within the CNS and their clearance routes from the CNS to the periphery (by modulating meningeal lymphatics, BBB-drainage and myeloid clearance function), on the peripheral marker levels. In a third step we plan to translate our findings to the patient using prospective multicenter cohorts (NationMS, Montréal-cohort, Nalo-MS).

• DFG Programme: CRC/Transregios
• Subproject of: TRR 128: Initiating/Effector versus Regulatory Mechanisms in Multiple Sclerosis - Progress towards Tackling the Disease
• Applicant Institution: Universität Münster
• Project Heads: Professor Dr. Timo Uphaus; Professorin Dr. Frauke Zipp