Therapies for multiple sclerosis: translational achievements and outstanding needs

•New therapies are on the horizon for multiple sclerosis disease mechanisms. •Immunotherapies are showing promise as treatments for multiple sclerosis. In recent years, multiple sclerosis (MS) research has progressed on several fronts, prompting numerous clinical trials, primarily for immunotherapeutics. Although several new therapies have been disappointing and some were revealed to have devastating side effects, others have shown benefits and all have generated valuable knowledge about the progression of MS, the key contributors to pathogenesis, and on natural surveillance mechanisms for brain infections. This makes now a useful time to take stock of recent advances in developing MS treatments and consider new approaches for adding information where the gaps are greatest – mainly in understanding the degenerative processes responsible for most of the long-term disability. Here, we summarize currently accepted therapeutic principles and the drugs in late stages of development, as well as spotlighting potential novel openings for future research. In recent years, multiple sclerosis (MS) research has progressed on several fronts, prompting numerous clinical trials, primarily for immunotherapeutics. Although several new therapies have been disappointing and some were revealed to have devastating side effects, others have shown benefits and all have generated valuable knowledge about the progression of MS, the key contributors to pathogenesis, and on natural surveillance mechanisms for brain infections. This makes now a useful time to take stock of recent advances in developing MS treatments and consider new approaches for adding information where the gaps are greatest – mainly in understanding the degenerative processes responsible for most of the long-term disability. Here, we summarize currently accepted therapeutic principles and the drugs in late stages of development, as well as spotlighting potential novel openings for future research. are mostly therapeutic antibodies directed against TNF, or TNF receptor proteins binding and neutralizing TNF, and are used, for example, to treat rheumatoid arthritis. a study performed to establish therapeutic and diagnostic approaches. Clinical trials are classified according to developmental stages (Phase I–IV) and have predefined trial endpoints and designs, which are usually certain clinical and paraclinical measures, for example, disability and radiological readouts. is an animal model of MS. EAE is classically induced by injecting rodents with myelin components emulsified in adjuvant. The resulting disease is characterized by myelin damage in the brain caused by inflammation and the animals develop various degrees of motor deficits such as limping. is a case–control study that compares a healthy control population with a disease cohort looking for genomic variants that are associated with the disease. is a noninvasive tool to visualize body organs. MRI is used in all medical fields for diagnostic purposes and for therapy monitoring. Using different sequences, for example, by alteration of spin relaxation times, the visualization of structures of interest can be optimized: for example, the so-called T1 sequence is an appropriate approach to determine brain areas with permanent neuronal damage (so-called 'black holes') in MS patients, whereas T2 sequences are used for quantification of demyelinated brain areas reflecting MS lesions. Additional MRI techniques such as DTI can be used for fine mapping of fibers and are used to observe neuronal connections within the brain. are immunoglobulins or their components detected in body fluids by protein electrophoresis. OCBs are indicative for immune reaction within the CNS and are seen in the CSF of up to 90% of MS patients, but also in other autoimmune conditions of the CNS, for example, neurosarcoidosis. is a single base in the DNA that differs from the usual base at that position. SNPs account for most of genomic variation in the genome.