Cladribine tablets in people with relapsing multiple sclerosis : A real-world multicentric study from southeast European MS centers

Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS).To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS).A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries.We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment.Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals

Konsensusprotokoll zur Standardisierung von Entnahme und Biobanking des Liquor cerebrospinalis

Die Erforschung von Biomarkern in Körperflüssigkeiten bei neurodegenerativen und neuroinflammatorischen Erkrankungen blickt auf eine langjährige Geschichte zurück. Dennoch werden nur wenige Liquor cerebrospinalis (Liquor)-Biomarker in der klinischen Praxis verwendet. Einer der problematischen Faktoren in der Liquorbiomarker-Forschung ist die eingeschränkte Aussagekraft von Studien aufgrund einer nicht ausreichend großer Anzahl von Proben, die in Studien von einzelnen Zentren akquiriert werden können. Deshalb ist die Kooperation zwischen mehreren Zentren erforderlich, um große Biobanken von definierten Proben zu etablieren. Standardisierte Protokolle für Biobanking sind unumgänglich, um die durch die größere Anzahl von Liquorproben gewonnene statistische Aussagekraft sicherzustellen und nicht durch mangelhafte Präanalytik einzuschränken. Hier wird ein Konsensusbericht über Leitlinien zu Liquorentnahme und Biobanking durch das BioMS-eu Netzwerk für Liquorbiomarker-Forschung in Multipler Sklerose präsentiert. Schwerpunkte des Berichts sind Liquorentnahme, präanalytische Faktoren und klinische sowie sonstige Informationen. Biobanking-Protokolle sind für Liquor-Biobanken im Rahmen der Erforschung jeder neurologischen Krankheit anwendba

Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies

There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. Anti-aquaporin-4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO), but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre-analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease

Kynurenines and Multiple Sclerosis: The Dialogue between the Immune System and the Central Nervous System

Multiple sclerosis is an inflammatory disease of the central nervous system, in which axonal transection takes place in parallel with acute inflammation to various, individual extents. The importance of the kynurenine pathway in the physiological functions and pathological processes of the nervous system has been extensively investigated, but it has additionally been implicated as having a regulatory function in the immune system. Alterations in the kynurenine pathway have been described in both preclinical and clinical investigations of multiple sclerosis. These observations led to the identification of potential therapeutic targets in multiple sclerosis, such as synthetic tryptophan analogs, endogenous tryptophan metabolites (e.g., cinnabarinic acid), structural analogs (laquinimod, teriflunomid, leflunomid and tranilast), indoleamine-2,3-dioxygenase inhibitors (1MT and berberine) and kynurenine-3-monooxygenase inhibitors (nicotinylalanine and Ro 61-8048). The kynurenine pathway is a promising novel target via which to influence the immune system and to achieve neuroprotection, and further research is therefore needed with the aim of developing novel drugs for the treatment of multiple sclerosis and other autoimmune diseases

Catecholamine levels in peripheral blood lymphocytes from multiple sclerosis patients

Circumstantial evidence suggests the involvement of sympathoadrenergic mechanisms in the progress of multiple sclerosis (MS). We p studied peripheral blood lymphocytes from MS patients. The levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and their metabolites in extracts of lymphocytes from 58 MS patients and 19 healthy controls were measured by using capillary electrophoresis. The MS patients were divided into clinical subgroups: a laboratory-supported definitive (first-attack) MS group, and a relapsing-remitting (RR) group in remission. The peripheral blood lymphocyte level of epinephrine was significantly higher in the first-attack MS patients (p = 0.028) than in the controls. However, the norepinephrine levels were significantly (p = 0.027) lower in the RR patients in remission. The catecholam ines are known to be able to affect the lymphocyte activity, both by stimulation and by immunosuppression. Our results suggest that the catecholamines are important regulators of lymphocyte activation in MS, and of potential importance as concerns new diagnostic and therapeutic methods. (C) 2002 Elsevier Science B.V. All rights reserved

Proteomic analysis of cerebrospinal fluid in a fulminant case of multiple sclerosis

Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject