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Jan Dörr,1,2 Karl Baum1 1Multiple Sclerosis Center, Neurology Department, Klinik Hennigsdorf, Hennigsdorf, 2NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Berlin, Germany Abstract: Multiple sclerosis (MS) is among the most common chronic inflammatory diseases of the central nervous system. Although not curable, the constantly increasing armamentarium of disease-modifying drugs now allows control of disease activity in many patients. The humanized monoclonal antibody alemtuzumab is a powerful drug licensed for the treatment of MS. Upon binding to the CD52 surface protein on CD4+ and CD8+ T cells, B cells, and monocytes, circulating CD52+ cells are eliminated via antibody- and complement-mediated lysis, and a less autoreactive adaptive immune system is reconstituted. The efficacy of alemtuzumab in terms of both clinical and magnetic resonance imaging outcomes has been demonstrated in several phase II/III trials including long-term extensions and follow-up studies. Treatment response to alemtuzumab is strongest as long as active inflammation is the predominant pathophysiological feature, and it is becoming less efficacious in neurodegeneration-dominated later stages of the disease. Thus, the optimal placement of alemtuzumab within treatment algorithms of MS is crucial. The impressive efficacy of alemtuzumab is counteracted by a less favorable safety profile. Besides usually manageable infusion-associated side effects, development of secondary autoimmunity in almost half of treated patients is the most disconcerting risk of alemtuzumab. The high frequency, the delayed occurrence, and the potentially severe course of secondary autoimmune diseases require awareness and a close long-term monitoring of patients treated with alemtuzumab. Biomarkers that would allow prediction of treatment response to alemtuzumab on the one hand and identification of patients at risk for the development of secondary autoimmune diseases on the other are not yet available. Thus, the overall success of alemtuzumab treatment critically depends on the patient selection. The aim of this article is therefore, to characterize the significance of alemtuzumab in the treatment of MS with a focus on the selection of the optimal patient. Keywords: multiple sclerosis, treatment, safety, efficacy, selection, benefit risk relation

Klaus Baum,1 Richard D Telford,2 Ross B Cunningham,3 1Trainingsinstitut Prof Baum, Köln, Germany; 2College of Medicine, Biology, and Environment, Australian National University, Canberra, ACT, Australia; 3The Fenner School of Environment and Society, Australian National University, Canberra, ACT, Australia Objective: Runners are prone to delayed onset muscle soreness (DOMS) during long distance training. This especially holds for unaccustomed training volumes at moderate to high intensities. We investigated the effects of a marine oil complex, PCSO-524®, derived from the New Zealand green-lipped mussel (formulated as Lyprinol® and Omega XL®) on DOMS after a 30 km training run. Methods: Initially, peak oxygen uptake of 32 distance runners (4 female, 28 male; median age 45 years, range 28–53) was measured on a treadmill with a 1.5 km hour-1 increase every 4 minutes starting from 8.5 km hour-1. At least 1-week after this initial test, they participated in a 30 km road run at a speed corresponding to about 70% of their individual peak oxygen uptake on a flat terrain. Before and after (0, 24, and 48 hours) the run, blood concentration of creatine kinase (CK) were measured and pain sensation was determined (pain scale from 0 = no pain to 10 = extremely painful). Runners were then matched in pairs based on maximal CK and peak oxygen uptake, and allocated randomly into two different groups. One group was supplemented with 400 mg per day of PCSO-524® for 11 weeks, the other group with an olive oil placebo. After that period, CK and pain sensations were remeasured following a second 30 km run at the same speed and on the same terrain. Results: The general pattern of soreness in the PCSO-524® supplemented group was reduced by 1.1 units (standard error 0.41) compared to the placebo (P < 0.05), the effects being greater in lesser trained runners (P < 0.05). CK levels were positively associated with pain sensation (P < 0.05), but trends toward lower CK in the PCSO-524® group, which were also more pronounced in the lesser trained runners, were not statistically significant. Conclusion: Pain sensations experienced by distance runners following a 30 km run were reduced by supplementation with the marine oil complex PCSO-524®, an effect which was greater in lesser trained runners. Keywords: running, marine oil, DOMS, creatine kinase