The Swedish MS registry ­ clinical support tool and scientific resource.

The Swedish MS registry (SMSreg) is designed to assure quality health care for patients with multiple sclerosis (MS). It has been active since 2001 and web-based since 2004. It runs on government funding only and is used in all Swedish neurology departments. The SMSreg currently includes data on 14,500 of Sweden's estimated 17,500 prevalent patients with MS. One important function of SMSreg, to which participation is voluntary, is to serve as a tool for decision support and to provide an easy overview of the patient information needed at clinical visits. This is its core feature and explains why the majority of Swedish MS specialists contribute data. Another success factor for SMSreg is that entered data can be readily accessed, either through a query function into Excel format or through a set of predesigned tables and diagrams in which parameters can be selected. Recent development includes a portal allowing patients to view a summary of their registered data and to report a set of patient-reported outcomes. SMSreg data have been used in close to 100 published scientific reports. Current projects include an incidence cohort (EIMS), post-marketing cohorts of patients on novel disease-modifying drugs (IMSE), and a prevalence cohort (GEMS). As these studies combine physical sampling and questionnaire data with clinical documentation and possible linkage to other public registries, together they provide an excellent platform for integrated MS research.

Natural Killer Cells in Multiple Sclerosis: Entering the Stage.

Studies investigating the immunopathology of multiple sclerosis (MS) have largely focused on adaptive T and B lymphocytes. However, in recent years there has been an increased interest in the contribution of innate immune cells, amongst which the natural killer (NK) cells. Apart from their canonical role of controlling viral infections, cell stress and malignancies, NK cells are increasingly being recognized for their modulating effect on the adaptive immune system, both in health and autoimmune disease. From different lines of research there is now evidence that NK cells contribute to MS immunopathology. In this review, we provide an overview of studies that have investigated the role of NK cells in the pathogenesis of MS by use of the experimental autoimmune encephalomyelitis (EAE) animal model, MS genetics or through ex vivo and in vitro work into the immunology of MS patients. With the advent of modern hypothesis-free technologies such as single-cell transcriptomics, we are exposing an unexpected NK cell heterogeneity, increasingly blurring the boundaries between adaptive and innate immunity. We conclude that unravelling this heterogeneity, as well as the mechanistic link between innate and adaptive immune cell functions will lay the foundation for the use of NK cells as prognostic tools and therapeutic targets in MS and a myriad of other currently uncurable autoimmune disorders.

Concise review: modeling multiple sclerosis with stem cell biological platforms: toward functional validation of cellular and molecular phenotypes in inflammation-induced neurodegeneration.

In recent years, tremendous progress has been made in identifying novel mechanisms and new medications that regulate immune cell function in multiple sclerosis (MS). However, a significant unmet need is the identification of the mechanisms underlying neurodegeneration, because patients continue to manifest brain atrophy and disability despite current therapies. Neural and mesenchymal stem cells have received considerable attention as therapeutic candidates to ameliorate the disease in preclinical and phase I clinical trials. More recently, progress in somatic cell reprogramming and induced pluripotent stem cell technology has allowed the generation of human "diseased" neurons in a patient-specific setting and has provided a unique biological tool that can be used to understand the cellular and molecular mechanisms of neurodegeneration. In the present review, we discuss the application and challenges of these technologies, including the generation of neurons, oligodendrocytes, and oligodendrocyte progenitor cells (OPCs) from patients and novel stem cell and OPC cellular arrays, in the discovery of new mechanistic insights and the future development of MS reparative therapies.