Improved and tailored therapies for patients with multiple sclerosis

Myhr is senior consultant and professor in Neurology, and has since 2001, directed the multiple sclerosis (MS) research group at Haukeland University Hospital and the University of Bergen (https://www.uib.no/fg/kgj-ms). He has previous chaired the first KG Jebsen centre for medical research, focusing on MS-biomarkers (2011-2016), and has since 2019 been the director of the first Norwegian centre for clinical treatment research, Neuro-SysMed.

The MS research group at Haukeland University Hospital and the University of Bergen has a long-standing tradition, since the early 1970s, for clinical epidemiology and immunology research in MS. This include studies of incidence and prevalence, and risk factors in MS, as well as immunological and genetic analysis of blood, cerebrospinal fluid (CSF) or brain tissue. The focus has been on aetiology, prognosis and pathogenesis of the disease.

Along with the introduction of disease modifying therapies in the early 1990s, we have increasingly organized and participated in national and international multicentre randomized clinical trials. This has naturally led into additional research activity focusing on symptom identification and therapy, rehabilitation, patients reported outcome measures, as well as health economy to evaluate the consequences of the disease to the patients, their families and society. Biomarker detection for early diagnosis, prognosis and treatment response for tailored therapy for individual patients is yet another research topic of the group.

The MS research group is highly dedicated for translational research to improve MS care, with a strong focus on treatment trials and biomarker detection.

The group is currently organizing a randomized clinical trial to evaluate the efficacy and safety of autologous haematological stem cell transplantation (HSCT) compared to standard high-efficacy therapies in MS. Haukeland University Hospital is the national centre for such MS-therapy in Norway, and we have recently reported efficacy and safety data from patients that received HSCT prior to the study start (Kvistad et al., 2019).

Another focus of our group has been B-cell depletion as early high-efficacy therapy in MS. Years before B-cell therapy was approved for MS, off label rituximab has been offered MS patients at Haukeland University Hospital. Based on this experience, a non-inferiority study comparing low-cost rituximab to the approved high-cost ocrelizumab is now underway. We have recently reported real world clinical experience of high efficacy and safety from rituximab therapy in relapsing-remitting MS (RRMS) (Torgauten et al., 2020 submitted).

Other important contributions from our group are milestone articles on axonal transection and cortical pathology in MS (Trapp et al., 1998, Bø et al., 2003a). Moreover reports of modifiable risk factors in MS, including vitamin D (Bjørnevik et al., 2015; Cortese et al., 2015), and bodyweight (Wesnes et al., 2015; Cortese et al., 2018). Importantly, vitamin D and body weight also seem to influence disease progression (Løken-Amsrud et al., 2012, Wergeland et al., 2011, Nystad et al., 2014) and therapy response (Kvistad et al., 2015; Bringeland et al. 2019).

Biomarkers for prognoses and treatment response are other important contributions from our research group. We, and others, have shown that CSF- and serum levels of neurofilament light chain (NFL) predict long-term prognosis (Bhan et al., 2018) and ongoing disease activity (Varhaug et al., 2017) in MS. More recently, we have presented data indicating that receptor occupancy may influence outcome of the high-efficacy natalizumab therapy in MS (Bringeland et al., 2020).

Symptomatic therapy, rehabilitation, patients reported outcomes measures and health economy have likewise been a prioritized area of research. This will further be integrated in the Neuro-SysMed research activity. We were pioneers in quality of life (QoL) research in MS (Nortvedt et al., 1999, 2000). Reports on physiotherapy rehabilitation (Smedal et al., 2011) as well as MS-symptoms related to fatigue (Smedal et al., 2011), sleep disturbances (Lunde et al., 2012) depression (Beiske et al., 2008), cognition (Cortese et al., 2016; Skorve et al., 2020), and bladder & sexual dysfunction (Nortvedt et al., 2007) have been important contributions from our group. Moreover, knowledge of long-terms consequences of the disease for the patients and their family, related to health economy and prognosis are important in the planning of the healthcare services (Svendsen et al., 2012; 2018; Myhr et al., 2001; Lunde et al., 2017; Grytten et al., 2019).

Aims

Research

National and international collaborators