124 Hits in 1.0 sec

Biomarkers in Multiple Sclerosis

Anu Paul, Manuel Comabella, Roopali Gandhi
2018 Cold Spring Harbor Perspectives in Medicine  
. , 2015 Ziemann et al. 2011; Stangel et al. 2013; Comabella and Montalban 2014; Gandhi 2015) .  ...  MS biomarkers classified into these categories are summarized in Figure 1 and Table 1 (modified from Comabella).  ... 
doi:10.1101/cshperspect.a029058 pmid:29500303 pmcid:PMC6396336 fatcat:6xspbz7x7fcq7mvu2xxb7pq5xu

Multiple sclerosis: current treatment algorithms

Jordi Río, Manuel Comabella, Xavier Montalban
2011 Current Opinion in Neurology  
Purpose of review Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system. Currently, there are different formulations approved for MS treatment and others are in different stages of investigation or awaiting approval by federal agencies. Recent findings All of these medications have demonstrated partial efficacy along with different sideeffect profiles. Nevertheless, many patients continue to experience disease activity while on treatment, and
more » ... s have been made on how the success of therapy in an individual patient can be assessed. Summary The option of individualized optimal treatment is progressively more complicated due to the growth of our knowledge about the natural behavior of MS and its different types and stages, the variety of different therapies, their strength and weaknesses, and their serious and sometimes life-threatening side-effects. In this review, we will summarize current algorithms and treatment options and also address clinical challenges we regularly face in arriving at treatment choices for our patients.
doi:10.1097/wco.0b013e328346bf66 pmid:21499098 fatcat:b2ey6tadlrbrdjq3tqqisx2zsa

Immunomodulatory Effects Associated with Cladribine Treatment

Nicolás Fissolo, Laura Calvo-Barreiro, Herena Eixarch, Ursula Boschert, Carmen Espejo, Xavier Montalban, Manuel Comabella
2021 Cells  
Cladribine is a synthetic deoxyadenosine analogue with demonstrated efficacy in patients with relapsing-remitting multiple sclerosis (MS). The main mechanism of action described for cladribine is the induction of a cytotoxic effect on lymphocytes, leading to a long-term depletion of peripheral T and B cells. Besides lymphocyte toxicity, the mode of action may include immunomodulatory mechanisms affecting other cells of the immune system. In order to induce its beneficial effects, cladribine is
more » ... hosphorylated inside the cell by deoxycytidine kinase (DCK) to its active form. However, the mechanism of action of cladribine may also include immunomodulatory pathways independent of DCK activation. This in vitro study was designed to explore the impact of cladribine on peripheral blood mononuclear cells (PBMC) subsets, and to assess whether the immunomodulatory mechanisms induced by cladribine depend on the activation of the molecule. To this end, we obtained PBMCs from healthy donors and MS patients and performed proliferation, apoptosis and activation assays with clinically relevant concentrations of cladribine in DCK-dependent and -independent conditions. We also evaluated the effect of cladribine on myeloid lineage-derived cells, monocytes and dendritic cells (DCs). Cladribine decreased proliferation and increased apoptosis of lymphocyte subsets after prodrug activation via DCK. In contrast, cladribine induced a decrease in immune cell activation through both DCK-dependent and -independent pathways (not requiring prodrug activation). Regarding monocytes and DCs, cladribine induced cytotoxicity and impaired the activation of classical monocytes, but had no effect on DC maturation. Taken together, these data indicate that cladribine, in addition to its cytotoxic function, can mediate immunomodulation in different immune cell populations, by regulating their proliferation, maturation and activation.
doi:10.3390/cells10123488 pmid:34943995 pmcid:PMC8700070 fatcat:ggua5ltfmvfivlpujeham5gtey

Pharmacogenomics in multiple sclerosis: getting the right medicine to the right patient

Manuel Comabella
2008 Therapy  
approaches to analyze data and differences in the experimental conditions, to name a few, may contribute to the discrepancies and high rates of false positives observed in these studies (as reviewed by Comabella  ... 
doi:10.2217/14750708.5.5.623 pmid:17899077 fatcat:jl525irbonbbzliyd3nxn4udsi

Chitinases and chitinase-like proteins as biomarkers in neurologic disorders

Rucsanda Pinteac, Xavier Montalban, Manuel Comabella
2020 Neurology: Neuroimmunology & Neuroinflammation  
Chitinases are hydrolytic enzymes widely distributed in nature. Despite their physiologic and pathophysiologic roles are not well understood, chitinases are emerging as biomarkers in a broad range of neurologic disorders, where in many cases, protein levels measured in the CSF have been shown to correlate with disease activity and progression. In this review, we will summarize the structural features of human chitinases and chitinase-like proteins and their potential physiologic and pathologic
more » ... unctions in the CNS. We will also review existing evidence for the role of chitinases and chitinase-like proteins as diagnostic and prognostic biomarkers in inflammatory, neurodegenerative diseases, and psychiatric disorders. Finally, we will comment on future perspectives of chitinase studies in neurologic conditions.
doi:10.1212/nxi.0000000000000921 fatcat:czwtgmzq3zbrfo7j3uucyedrri

Teriflunomide in Patients with Relapsing–Remitting Forms of Multiple Sclerosis

Andrew Chan, Jérôme de Seze, Manuel Comabella
2016 CNS Drugs  
Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi, and Teva.  ... 
doi:10.1007/s40263-015-0299-y pmid:26758290 pmcid:PMC4733135 fatcat:nfuvxqyxgnaj7m74pk7btfrjz4

Chitinases and chitinase-like proteins as biomarkers in neurologic disorders

Rucsanda Pinteac, Xavier Montalban, Manuel Comabella
2020 Neurology: Neuroimmunology & Neuroinflammation  
Comabella, MD, PhD Neurology: Neuroimmunology & Neuroinflammation | Volume 8, Number 1 | January 2021 Neurology: Neuroimmunology & Neuroinflammation | Volume 8, Number  ...  Cemcat), Institut de Recerca, Hospital Vall d'Hebron, Barcelona, Spain Drafting/revising the manuscript for content, including medical writing for content, and study concept Xavier Montalban, MD, PhD Manuel  ... 
doi:10.1212/nxi.0000000000000921 pmid:33293459 pmcid:PMC7803328 fatcat:jlv7re6hxrcrxmny46ibsgdoim

Angiogenin in the Neurogenic Subventricular Zone After Stroke

Marina Gabriel-Salazar, Ting Lei, Alba Grayston, Carme Costa, Esperanza Medina-Gutiérrez, Manuel Comabella, Joan Montaner, Anna Rosell
2021 Frontiers in Neurology  
Ischemic stroke is a leading cause of death and disability worldwide with effective acute thrombolytic treatments. However, brain repair mechanisms related to spontaneous or rehabilitation-induced recovery are still under investigation, and little is known about the molecules involved. The present study examines the potential role of angiogenin (ANG), a known regulator of cell function and metabolism linked to neurological disorders, focusing in the neurogenic subventricular zone (SVZ).
more » ... in expression was examined in the mouse SVZ and in SVZ-derived neural stem cells (NSCs), which were exposed to exogenous ANG treatment during neurosphere formation as well as in other neuron-like cells (SH-SY5Y). Additionally, male C57Bl/6 mice underwent a distal permanent occlusion of the middle cerebral artery to study endogenous and exercise-induced expression of SVZ-ANG and neuroblast migration. Our results show that SVZ areas are rich in ANG, primarily expressed in DCX+ neuroblasts but not in nestin+NSCs. In vitro, treatment with ANG increased the number of SVZ-derived NSCs forming neurospheres but could not modify SH-SY5Y neurite differentiation. Finally, physical exercise rapidly increased the amount of endogenous ANG in the ipsilateral SVZ niche after ischemia, where DCX-migrating cells increased as part of the post-stroke neurogenesis process. Our findings position for the first time ANG in the SVZ during post-stroke recovery, which could be linked to neurogenesis.
doi:10.3389/fneur.2021.662235 fatcat:povwp53k7jad5jzwsjn4ytsbk4

Chitinase 3-like 1 is neurotoxic in primary cultured neurons

Clara Matute-Blanch, Laura Calvo-Barreiro, Iria Carballo-Carbajal, Ricardo Gonzalo, Alex Sanchez, Miquel Vila, Xavier Montalban, Manuel Comabella
2020 Scientific Reports  
Chitinase 3-like 1 (CHI3L1) is known to play a role as prognostic biomarker in the early stages of multiple sclerosis (MS), and patients with high cerebrospinal fluid CHI3L1 levels have an increased risk for the development of neurological disability. Here, we investigated its potential neurotoxic effect by adding recombinant CHI3L1 in vitro to primary cultures of mouse cortical neurons and evaluating both neuronal functionality and survival by immunofluorescence. CHI3L1 induced a significant
more » ... urite length retraction after 24 and 48 hours of exposure and significantly reduced neuronal survival at 48 hours. The cytotoxic effect of CHI3L1 was neuron-specific and was not observed in mouse immune or other central nervous system cells. These results point to a selective neurotoxic effect of CHI3L1 in vitro and suggest a potential role of CHI3L1 as therapeutic target in MS patients.
doi:10.1038/s41598-020-64093-2 pmid:32346016 fatcat:pxsoxurkjrcm3e5lwrntb2fjoa

Peripheral Myeloid-Derived Suppressor Cells are good biomarkers of the efficacy of Fingolimod in Multiple Sclerosis [article]

Celia Camacho-Toledano, Isabel Machin-Diaz, Leticia Calahorra, Maria Cabanas, David Otaegui, Tamara Castillo-Trivino, Luisa Maria Villar, Lucienne Costa-Frossard, Manuel Comabella, Luciana Midaglia, Jose Manuel Garcia-Dominguez, Jennifer Garcia-Arocha (+2 others)
2022 bioRxiv   pre-print
The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition of inhibiting T cell egression from lymph nodes, fingolimod promotes the immunosuppressive activity of Myeloid-Derived Suppressor Cells (MDSCs), a cell type that
more » ... n be used as a biomarker of disease severity, and of the degree of demyelination and extent of axonal damage in MS. In the present study, we have assessed whether the abundance of circulating monocytic-MDSCs (M-MDSCs) may represent a useful biomarker of fingolimod efficacy. As such, blood immune cells were analyzed at disease onset in the experimental autoimmune encephalomyelitis (EAE) MS mouse model. Fingolimod treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. The data obtained indicated that the M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e. patients who met at least two of the criteria used to define non-evidence of disease activity (NEDA-3) 12 months after treatment, providing relevant information of intention-to-treat MS patients. Collectively, our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod.
doi:10.1101/2022.08.22.504792 fatcat:j76ssgt2rzbxnf3yk6nmvw2fsa

Up-regulation of inducible heat shock protein-70 expression in multiple sclerosis patients

María José Mansilla, Manuel Comabella, Jordi Río, Joaquín Castilló, Mireia Castillo, Roland Martin, Xavier Montalban, Carmen Espejo
2013 Autoimmunity  
Inducible heat shock protein (HSP)70 (HSP70-1A and HSP70-1B proteins) is a chaperone responsible for assisting proper protein folding. Following stress conditions, HSP70 is highly up-regulated to mediate cytoprotective functions. In addition, HSP70 is able to trigger innate and adaptive immune responses that promote the immune recognition of antigens and to act as a cytokine when it is released. The data in the literature are controversial with regard to expression studies in peripheral blood
more » ... nonuclear cells (PBMCs). In the present study, we aimed to examine if alterations of HSP70-1A/B expression are involved in the autoimmune pathogenesis of multiple sclerosis (MS). We determined both mRNA and protein expression in PBMCs of MS patients and healthy donors (HDs). We found a baseline increased expression of the HSPA1A gene in PBMCs from MS patients compared with HDs. Gene expression findings were associated with an increased protein expression of HSP70-1A/B in T lymphocytes (CD4+ and CD8+) and monocytes from MS patients under basal conditions that may reflect the immunological activation occurring in MS patients. We also provided evidence that heat shock (HS) stimulus induced HSP70-1A/B protein expression in HDs and MS patients, and that HS-induced HSP70-1A/B protein expression in monocytes correlated with the number of T2 lesions at baseline in MS patients. However, after lipopolysaccharide inflammatory stimulus, monocytes from MS patients failed to induce HSP70-1A/B protein expression. Our data hint at altered immune responses in MS and may indicate either a state of chronic stress or increased vulnerability to physiological immune responses in MS patients.
doi:10.3109/08916934.2013.866104 pmid:24328534 fatcat:apmbxxtyu5dslcy4bamj3jzlue

Baseline Gene Expression Signatures in Monocytes from Multiple Sclerosis Patients Treated with Interferon-beta

Marta F. Bustamante, Ramil N. Nurtdinov, Jordi Río, Xavier Montalban, Manuel Comabella, Lionel G. Filion
2013 PLoS ONE  
Citation: Bustamante MF, Nurtdinov RN, Río J, Montalban X, Comabella M (2013) Baseline Gene Expression Signatures in Monocytes from Multiple Sclerosis Patients Treated with Interferon-beta.  ... 
doi:10.1371/journal.pone.0060994 pmid:23637780 pmcid:PMC3630153 fatcat:fbd4te4qnzc23fyi2jivlumz44

Lesion topographies in multiple sclerosis diagnosis

Georgina Arrambide, Mar Tintore, Cristina Auger, Jordi Río, Joaquín Castilló, Angela Vidal-Jordana, Ingrid Galán, Carlos Nos, Manuel Comabella, Raquel Mitjana, Patricia Mulero, Andrea de Barros (+5 others)
2017 Neurology  
Manuel Comabella contributed to the acquisition and analysis of data for the work; participated in the drafting of the work and revised it for important intellectual content; and gave final approval of  ... 
doi:10.1212/wnl.0000000000004715 pmid:29101276 pmcid:PMC5719929 fatcat:c7iosjzn6bcz3i6xpexa5g5fme

Novel Insights into the Multiple Sclerosis Risk GeneANKRD55

Aitzkoa Lopez de Lapuente, Ana Feliú, Nerea Ugidos, Miriam Mecha, Jorge Mena, Ianire Astobiza, José Riera, Francisco Carillo-Salinas, Manuel Comabella, Xavier Montalban, Iraide Alloza, Carmen Guaza (+1 others)
2016 Journal of Immunology  
doi:10.4049/jimmunol.1501205 pmid:27183579 fatcat:wdc2b4ljmjeybmnfga2flvr5ha

Metabolomic signatures associated with disease severity in multiple sclerosis

Pablo Villoslada, Cristina Alonso, Ion Agirrezabal, Ekaterina Kotelnikova, Irati Zubizarreta, Irene Pulido-Valdeolivas, Albert Saiz, Manuel Comabella, Xavier Montalban, Luisa Villar, Jose Carlos Alvarez-Cermeño, Oscar Fernández (+3 others)
2017 Neurology: Neuroimmunology & Neuroinflammation  
Objective: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. Methods: We studied 2 cohorts of patients with MS: a retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for
more » ... presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS). Metabolomic profiling (lipids and amino acids) was performed by ultra-high-performance liquid chromatography coupled to mass spectrometry in serum samples. Data analysis was performed using parametric methods, principal component analysis, and partial least square discriminant analysis for assessing the differences between cases and controls and for subgroups based on disease severity. Results: We identified metabolomics signatures with high accuracy for classifying patients vs controls as well as for classifying patients with medium to high disability (EDSS .3.0). Among them, sphingomyelin and lysophosphatidylethanolamine were the metabolites that showed a more robust pattern in the time series analysis for discriminating between patients and controls. Moreover, levels of hydrocortisone, glutamic acid, tryptophan, eicosapentaenoic acid, 13S-hydroxyoctadecadienoic acid, lysophosphatidylcholines, and lysophosphatidylethanolamines were associated with more severe disease (non-relapse-free or increase in EDSS). Conclusions: We identified metabolomic signatures composed of hormones, lipids, and amino acids associated with MS and with a more severe course. GLOSSARY ANOVA 5 analysis of variance; EDSS 5 Expanded Disability Status Scale; m/z 5 mass-to-charge; MRS 5 magnetic resonance spectroscopy; MS 5 multiple sclerosis; OPLS 5 orthogonal projection to latent structures; PCA 5 principal components analysis; Rt 5 retention time; SME 5 splines mixed effects; TOF 5 time of flight; UHPLC-MS 5 ultra-high-performance liquid chromatography coupled to mass spectrometry.
doi:10.1212/nxi.0000000000000321 pmid:28180139 pmcid:PMC5278923 fatcat:jjyl4fi5vjfl5dxi4hqn5spege
« Previous Showing results 1 — 15 out of 124 results