The project activities of the Multiple Sclerosis (MS) Research Group aim to support and meet the main objective of Neuro-SysMed to generate improved and tailored treatment strategies for patients with MS. Some projects are a direct result from the NeuroSysMed funding, and others are a part of the longterm commitment of the group for improved therapy and care for MS patients, and thus are important prerequisites for the Neuro-SysMed centre.

The group is currently recruiting patients into four investigator sponsored clinical trials. The RAM-MS study evaluates the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) compared to high-efficacy disease modifying therapies (DMT) in relapsing-remitting MS (RRMS) patient with breakthrough disease activity. The OVERLORD-MS study evaluates and compares the efficacy and safety of rituximab and ocrelizumab in newly diagnosed RRMS patients. The COVID-19 vaccine response study evaluates the impact of various DMTs on the vaccination response in MS patients. The SMARTMS study aims to evaluate the regenerative effect of mesenchymal autologous stem cells in progressive MS. This latter study has received approval from the Norwegian Medical Agency and the Ethical Committee, but the start is put on hold due to COVID-19 restrictions for the partner in Ulm, Germany. The group is however pre-screening patients to be ready for the start-up. In addition, they are also national coordinator for three industry sponsored multicentre randomized clinical trials, and recruiting site for another.

In collaboration with the biomarker group, the MS group is currently phenotyping stem cells and immune cells from patients included in the ongoing clinical trials, aiming to identify biomarkers for tailored dosing or patient selection. In other studies, they have evaluated biomarkers of treatment response of natalizumab as well as dimethyl fumarate and teriflunomide. similarly, the use of neurofilament (NFL) and magnetic resonance imaging (MRI) are used to evaluate treatment response and disease progression. The impact of modifiable lifestyle factors are also evaluated, related to treatment efficacy and long-term prognoses, aiming for improved and personalised treatment strategies in MS.

A sensitive and clinical practical screening instrument for early detection of disabling symptoms like cognitive dysfunction is another important research focus with direct impact for the clinical trial efficacy endpoints. Thus, the Norwegian translation of the brief international cognitive assessment for multiple sclerosis (BICAMS) is currently included in the clinical trials.

Registry and epidemiological studies to evaluate possible risk factors and comorbidities have been a long-term commitment for the research group. Recent data on cancer frequency in MS calls or further studies both on the aetiology of the disease, and risk stratification for immunotherapy.

Preclinical studies evaluating effects from vitamin D on remyelination (repair) in animal models, as well as biomarker discovery studies in these animal models and the cerebrospinal fluid from MS patients are other prioritized projects in the group. They also use animal models in feasibility studies of mesenchymal stem cells as a regenerative therapy in progressive MS.

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. Norborg H, Riise T, Myhr KM, Grytten N, Wergeland S. Real-world discontinuation of teriflunomide and dimethyl fumarate in multiple sclerosis. Mult Scler J Exp Transl Clin 2020/2021 – in press.
4. Varhaug KN, Torkildsen Ø, Myhr KM, Vedeler CA. Neurofilament Light Chain as a Biomarker in Multiple Sclerosis. Front Neurol 2019;10:338. PMID: 31024432
5. Lie IA, Weeda MM, Mattiesing RM, Mol MAE, Pouwels PJW, Barkhof F, Torkildsen Ø, Bø L, Myhr KM, Vrenken H. The relationship between white matter lesions and grey matter atrophy in multiple sclerosis. Neurology 2020/2021, submitted
6. Wesnes K, Myhr KM, Riise T, Kvistad SS, Torkildsen Ø, Wergeland S, Holmøy T, Midgard R, Bru A, Edland A, Eikeland R, Gosal S, Harbo HF, Kleveland G, Sørenes YS, Øksendal N, Bjørnevik K. Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis. Mult Scler Relat Disord 2021;50:102801. PMID: 33636616
7. Skorve E, Lundervold AJ, Torkildsen Ø, Myhr KM. A two-year longitudinal follow-up of cognitive performance assessed by BICAMS in newly diagnosed patients with MS. Mult Scler Relat Disord 2020;46:102577. PMID: 33296975
8. Grytten N, Myhr KM, Celius EG, Benjaminsen E, Kampman M, Midgard R, Vatne A, Aarseth JH, Riise T, Torkildsen Ø. Risk of cancer among multiple sclerosis patients, siblings, and population controls: A prospective cohort study. Mult Scler 2020;26:1569-1580. PMID: 31573834
9. Grytten N, Myhr KM, Celius EG, Benjaminsen E, Kampman MT, Midgard R, Vatne A, Aarseth JH, Riise T, Torkildsen Ø. Incidence of cancer in multiple sclerosis before and after the treatment era– a registry- based cohort study. Mult Scler J Exp Transl Clin 2020/2021 – submitted.
10. Nystad AE, Lereim RR, Wergeland S, Oveland E, Myhr KM, Bø L, Torkildsen Ø. Fingolimod downregulates brain sphingosine-1-phosphate receptor 1 levels but does not promote remyelination or neuroprotection in the cuprizone model. J Neuroimmunol 2020;339:577091. PMID: 31739156
11. Oveland E, Ahmad I, Lereim RR, Kroksveen AC, Barsnes H, Guldbrandsen A, Myhr KM, Bø L, Berven FS, Wergeland S. Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis. Sci Rep 2020/2021 in press
12. 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

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