The Biomarker Group currently focuses on translational single cell omics research in two stem cell intervention trials, inspired by the potentially large benefits of the two stem cell clinical trials organized by the MSgroup at Neuro-SysMed. The RAM-MS study seeks to reconstitute the immune system of RRMS patients with a distinct inflammatory component by hematopoietic stem cell transplantation (HSCT). The SMART-MS study seeks to induce the endogenous regenerative potential in the central nervous system (CNS) of MS patients with a distinct neuro-degenerative disease
course, PPMS and SPMS, with mesenchymal stem cells (MSC).

The group is developing quality controlled diagnostic and biomarker assays based on state of the art technologies. They use mass cytometry and flow cytometry for deep immune phenotyping to study the immune response in blood and CSF and the composition of cell products to evaluate treatment safety and response. They develop functional and quantitative assays for antibody based therapy such as receptor occupancy for mass cytometry to monitor drug efficacy in patients. The group further develops and establishes CSF and serum biomarker assays such as neurofilamant (NFL) and IgG bands. Based on quanterix technology, they measure NFL-light chain in serum samples from patients to monitor treatment response and disease progression in neurological diseases. In collaboration with the Department of Medical Biochemistry and Pharmacology, they have established a very sensitive capillary gel electrophoresis method that substantially increased sensitivity and specificity of oligoclonal immunoglobulins in CSF of patients with MS and other neuroinflammatory diseases. Currently, they are establishing a method to test pharmacological
profiles of drugs and anti-drug antibodies of biological medications, such as for anti-CD20 antibodies used to treat patients with MS.

The group contributes with standard operating procedures for laboratory manuals in clinical trials and has optimized standard protocols for biobanking of patient materials in clinical trials at Neuro-SysMed. In addition, the group is working on a set of important proteins, called cerebellar degeneration proteins (CDR1, CDR2, CDR2L), which they have localized to important cell organelles that are essential for neuronal functions, being nuclear speckles, Golgi apparatus and mitochondrial transport. These proteins will be further characterized as potential biomarkers for neurodegenerative diseases. The group further studies the brain microenvironment in post-mortem tissues. They use state of the art imaging mass cytometry to characterize the brain microenvironment at unpresented resolution. They are particularly interested in immunologically competent cells in brain, such as microglia and astrocytes, and study the cell interactions to investigate disease mechanisms and new treatment targets.

Selected Key Publications

1. Bringeland GH, Blaser N, Myhr KM, Vedeler CA, Gavasso S. Wearing-off at the end of natalizumab dosing intervals is associated with low receptor occupancy. Neurol Neuroimmunol Neuroinflamm. 2020;7:e678. PMID: 32019768
2. Bringeland GH, Myhr KM, Vedeler CA, Gavasso S. Wearing-off at the end of natalizumab dosing interval and risk of MS disease activity: A prospective 1-year follow-up study. J Neurol Sci 2020;415:116880. PMID: 32413799
3. Varhaug KN, Torkildsen Ø, Myhr KM, Vedeler CA. Neurofilament Light Chain as a Biomarker in Multiple Sclerosis. Front Neurol 2019;10:338. PMID: 31024432
4. Mosleth EF, Vedeler CA, Liland KH, McLeod A, Bringeland GH, Kroondijk L, Berven FS, Lysenko A, Rawlings CJ, Eid KE, Opsahl JA, Gjertsen BT, Myhr KM, Gavasso S. Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis. Sci Rep 2021;11:4087. PMID: 33602999
5. Herdlevaer I, Kråkenes T, Schubert M, Vedeler CA Localization of CDR2L and CDR2 in paraneoplastic cerebellar degeneration. Ann Clin Transl Neurol 2020;7:2231-2242. doi: 10.1002/acn3.51212.
6. Varhaug KN, Kråkenes T, Alme MN, Vedeler CA, Bindoff LA. Mitochondrial complex IV is lost in neurons in the cuprizone mouse model. Mitochondrion 2020 ;50:58-62.
7. Gavasso S, Bringeland GH, Tárnok A. Receptor occupation in the fjords. Cytometry A 2019 ;95:1044-1045. PMID: 31617331
8. Gullaksen SE, Bader L, Hellesøy M, Sulen A, Fagerholt OHE, Engen CB, Skavland J, Gjertsen BT, Gavasso S. Titrating Complex Mass Cytometry Panels. Cytometry A 2019;95:792-796. PMID: 30964237
9. Bringeland GH, Bader L, Blaser N, Budzinski L, Schulz AR, Mei HE, Myhr KM, Vedeler CA, Gavasso S. Optimization of Receptor Occupancy Assays in Mass Cytometry: Standardization Across Channels with QSC Beads. Cytometry A 2019;95:314-322. PMID: 30688025

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