Nasrin Asgari Professor, M.D., Ph.D., DMSc
Nasrin Asgari
Institute of Regional Health Research, & Institute of Molecular Medicine, University of Southern Denmark
| Projekt styring | ||
| Projekt status | Open | |
| Data indsamlingsdatoer | ||
| Start | 01.01.2020 | |
| Slut | 31.10.2030 | |
Biomarkers of blood-brain barrier disruption in inflammatory demyelinating disease of the central nervous system
Short summary
Disruption of the blood brain barrier (BBB) correlates with clinical exacerbation in inflammatory demyelinating diseases (IDD). Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix (ECM) protein. In this multidisciplinary project we provide evidence that MFAP4 levels in cerebrospinal fluid (CSF) are significantly altered in patients with IDD compared to controls. MFAP4 is expressed in in the optic nerve and brain. For validation, samples are provided from a multitude of centers
Rationale
Inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS) constitute a group of autoimmune diseases with unknown etiology, which are increasingly recognized as major causes of disability in Europe including Denmark. The three best-defined IDDs are multiple sclerosis (MS), and MS-related diseases as aquaporin-4-IgG positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD).MS and MS-related diseases of the CNS are characterized by the destruction of the myelin sheath of axons, leading to widespread loss of neuronal function with a variable degree of axonal injury and loss, resulting in disability. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein. As a novel observation, our group recently reported data on expression of MFAP4, which was localized to meninges and vascular/perivascular spaces, intense in the optic nerve. At sites of active inflammation, MFAP4 reactivity was reduced in acute stage in the tissues. cerebrospinal fluid (CSF) MFAP4 levels were reduced during relapse. These data suggest that MFAP4 may serve as a potential biomarker of disease activity. Nonetheless, the potential role of MFAP4 in the acute stage requires further investigation. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are released into the CSF and serum following CNS injury. We propose that levels of MFAP4 is correlated with NfL and GFAP levels and clinical outcomes. The goal of this project is to address, whether the integrity of the BBB depends on the cleaving of MFAP4, furthermore whether MFAP4 as an inflammatory marker is altered in CSF and may act as a biomarker for BBB breakdown and predict the onset of disease activity
Description of the cohort
Paired CSF and serum samples taken prior to treatment were provided. Samples from patients with acute optic neuritis (ON) were from the Region of Southern Denmark and from Rigshospitalet - Glostrup. In addition, Germany (Charite University, Berlin), South Korea (Goyang), USA (Mayo Clinic, Minnesota and University of Colorado, Denver), France (Lyon) and Region of Southern Denmark have provided ON, multiple sclerosis (MS), anti-aquaporin-4 positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and double-seronegative patients for the study.
Data and biological material
cerebrospinal fluid and blood. Detection of biomarkers data from the patient journal and REDCap
Publications associated with the project