Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial

Cadavid, Diego; Mellion, Michelle; Hupperts, Raymond; Edwards, Keith R.; Calabresi, Peter A.; Drulović, Jelena; Giovannoni, Gavin; Hartung, Hans‐Peter; Arnold, Douglas L.; Fisher, Elizabeth; Rudick, Richard A.; Mi, Sha; Chai, Yi; Li, Jie; Zhang, Yiwei; Cheng, Wenting; Xu, Lei; Zhu, Bing; Green, Susan M; Chang, Ih; Deykin, Aaron; Sheikh, Sarah; Morales, E.; Khedr, Abdullatif Al; Ampapa, Radek; Arroyo, Rafael; Belkin, Martin; Bonek, Robert; Boyko, A. N.; Capra, Ruggero; Centonze, Diego; Clavelou, Pierre; Debouverie, Marc; Evangelou, Nikos; Evdoshenko, Evgeniy; Fernández, Óscar; Sánchez, Victoria Fernández; Freedman, Mark S.; Freedman, S. O.; Fryze, Waldemar; García‐Merino, Antonio; Gavric-Kezic, M.; Ghezzi, A.; Gout, Olivier; Grimaldi, Luigi Maria Edoardo; Hendin, Barry; Hertmanowska, Hanka; Hintzen, Rogier Q.; Hradílek, Pavel; Ilkowski, Jan; Ivashinenkova, Evelina; Izquierdo, Guillermo; Jacques, François; Jakab, Gábor; Хабиров, Ф. А.; Kłodowska-Duda, Gabriela; Komoly, S.; Kostić, Smiljana; Kovářová, Ivana; Kremenchuzky, Marcelo; LaGanke, Christopher; Lapierre, Yves; Maciejowski, Maciej; Maison, Francois Grand’; Marfia, Girolama Alessandra; Yélamos, Sergio Martínez; Meluzínová, Eva; Montalbán, Xavier; Murray, Ronald S.; Naismith, Robert T.; Newsome, Scott D.; Nguyen, Viet A.; Oreja, Delia; Pardo, Gabriel; Pasechnik, Elena S.; Patti, Francesco; Potemkowski, Andrzej; Прокопенко, С. М.; Qian, Peiqing; Rodríguez‐Antigüedad, Alfredo; Rossman, Howard; Rózsa, Csilla; López, Fernando Sánchez; Selmaj, Krzysztof; Silber, Eli; Stępień, Adam; Stepniewska, Anna; Świat, Maciej; Tončev, Gordana; Tourbah, Ayman; Trushnikova, Tatyana; Uccelli, Antonio; Vachová, Marta; Vališ, Martin; Vécsei, László; Wiertlewski, Sandrine; Zaffaroni, Mauro; Zieliński, Tomasz

doi:10.1016/s1474-4422(19)30137-1

Cited by 137 publications

(100 citation statements)

References 29 publications

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“…OPCs have recently been shown to potentially play an active role in the pathology of MS and have been implicated in the progression of Alzheimer's disease 17,20,63 . Given these associations with Alzheimer's disease and MS, and the known role of clusterin in multiple CNS pathologies, interrogating the functions of this cluster of OPCs may be particularly important in revealing novel ways OPCs help maintain homeostasis and how they subsequently may be playing an active role in contributing to or protecting against CNS pathology [63][64][65][66] .…”

Section: Discussionmentioning

confidence: 99%

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner

Beiter

Fernández-Castañeda

Rivet-Noor

et al. 2020

Preprint

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Oligodendrocyte progenitor cells (OPCs) are a mitotically active population of glia that comprise approximately 5% of the adult brain. OPCs maintain their proliferative capacity and ability to differentiate in oligodendrocytes throughout adulthood, but relatively few mature oligodendrocytes are produced following developmental myelination. Recent work has begun to demonstrate that OPCs likely perform multiple functions in both homeostasis and disease, and can significantly impact behavioral phenotypes such as food intake and depressive symptoms. However, the exact mechanisms through which OPCs might influence brain function remains unclear. In this work, we demonstrate that OPCs are transcriptionally diverse and separate into three distinct populations in the homeostatic brain. These three groups show distinct transcriptional signatures and enrichment of biological processes unique to individual OPC populations. We have validated these OPC populations using multiple methods, including multiplex RNA in situ hybridization and RNA flow cytometry. This study provides an important resource that profiles the transcriptome of adult OPCs and will provide a significant foundation for further investigation into novel OPC functions.

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Section: Discussionmentioning

confidence: 99%

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner

Beiter

Fernández-Castañeda

Rivet-Noor

et al. 2020

Preprint

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“…However, Opicinumab did not lead to any improvement or slowdown in disability progression in MS patients. Interestingly, a more detailed analysis of the data based on magnetic resonance imaging and disease duration allowed to identify a subgroup of patients who may have an enhanced response to Opicinumab 16 …”

Section: Introductionmentioning

confidence: 99%

LINGO family receptors are differentially expressed in the mouse brain and form native multimeric complexes

et al. 2020

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Leucine‐rich repeat and immunoglobin‐domain containing (LRRIG) proteins that are commonly involved in protein‐protein interactions play important roles in nervous system development and maintenance. LINGO‐1, one of this family members, is characterized as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte precursor cell (OPC) differentiation into mature myelinating oligodendrocytes. Three LINGO‐1 homologs named LINGO‐2, LINGO‐3, and LINGO‐4 have been described. However, their relative expression and functions remain unexplored. Here, we show by in situ hybridization and quantitative polymerase chain reaction that the transcripts of LINGO homologs are differentially expressed in the central nervous system. The immunostaining of brain slices confirmed this observation and showed the co‐expression of LINGO‐1 with its homologs. Using BRET (bioluminescence resonance energy transfer) analysis, we demonstrate that LINGO proteins can physically interact with each of the other ones with comparable affinities and thus form the oligomeric states. Furthermore, co‐immunoprecipitation experiments indicate that LINGO proteins form heterocomplexes in both heterologous systems and cortical neurons. Since LINGO‐1 is a promising target for the treatment of demyelinating diseases, its ability to form heteromeric complexes reveals a new level of complexity in its functioning and opens the way for new strategies to achieve diverse and nuanced LINGO‐1 regulation.

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“…Tais variáveis podem, por vezes, ser controladas pelo pesquisador. Por exemplo, no estudo de Cadavid et al 1 , a variável dependente é o desfecho 'melhora confirmada da deficiência' e uma das variáveis independentes é o grupo ao qual o paciente é alocado (tratamento com opicinumab ou placebo).…”

Section: O Que São Medidas Dependentes E Independentes?unclassified

Modelagem estatística: Perguntas que você sempre quis fazer, mas nunca teve coragem

Leotti

Mancuso

Borges

et al. 2020

CBR

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356Modelagem estatística: perguntas que você sempre quis fazer, mas nunca teve coragem Statistical modeling: questions you have always wanted to ask but never had the courage to RESUMO Dando continuidade aos artigos da série "Perguntas que você sempre quis fazer, mas nunca teve coragem", que tem como objetivo responder e sugerir referências para o melhor entendimento das principais dúvidas dos pesquisadores do Hospital de Clínicas de Porto Alegre sobre estatística, este quarto artigo se propõe a responder às principais dúvidas levantadas sobre modelagem estatística. São discutidas questões referentes à classificação de variáveis em independentes e dependentes, diferenças entre correlação, associação e regressão, os principais tipos de regressão e quais etapas são necessárias na construção de modelos. Os conceitos são abordados numa linguagem acessível ao público leigo e diversas referências são sugeridas para os curiosos em relação ao tema. Palavras-chave: Modelo ABSTRACTContinuing the series of articles "Questions you have always wanted to ask but never had the courage to," which aims to answer the most common questions of researchers at Hospital de Clínicas de Porto Alegre regarding statistics and to suggest references for a better understanding, this forth article addresses the topic of statistical modeling. Questions about classification of variables as dependent or independent, differences between correlation, association and regression, types of regression and steps for statistical modeling are discussed. The concepts are explained in plain language for lay readers and several references are suggested for those curious about the topic.

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Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial

Cited by 137 publications

References 29 publications

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner

LINGO family receptors are differentially expressed in the mouse brain and form native multimeric complexes

Modelagem estatística: Perguntas que você sempre quis fazer, mas nunca teve coragem

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