D: Wet biomarkers最新文献

{"title":"D03 Circular rnas as potential biomarkers in huntington’s disease pathogenesis","authors":"M. Pellegrini, J. Döring, G. Bergonzoni, F. Perrone, Giulia Cardamone, A. Monziani, F. Leva, Michele Arnoldi, Sabrina Maffi, S. Migliore, Ludovica C Busi, R. Asselta, E. Dassi, F. Squitieri, M. Biagioli","doi":"10.1136/jnnp-2021-ehdn.34","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.34","url":null,"abstract":"Background With the development of new therapies entering clinical trials for HD, there is an increasing need to develop and validate biomarkers in accessible biofluids, such as blood, to follow disease progression and predict treatment outcomes. Some biomarkers do exist; however, reliable and readily available additional ones will be crucial in assessing the pathogenic process and pharmacologic responses to therapeutic interventions. Aims For the first time in HD, we detect and characterize circRNAs in peripheral blood of a cohort of gender and age-matched controls and HD patients at various stages of the disease. We studied their potential as biomarkers by evaluating their correlation with disease progression and the size of the CAG repeat. Methods 50 blood samples were collected from both HD patients and a healthy cohort of individuals. Total RNA was used for RNA sequencing, and the obtained data were aligned with STAR. DCC program was used to quantify circRNAs and CircTest (R package) to identify differentially expressed circRNA between different disease stages and controls. CAG repeat size correlation was also tested. To validate our findings, candidate circRNAs were quantified via RT-qPCR in our samples. Results Our study led to the discovery of 7, stringently defined circRNAs that possess 3 characteristics: differentially expressed in HD patients (all up-regulated, p-value 0.3 and p-value Conclusions We identified for the first time circRNAs whose expression increases in the blood of HD patients. Currently, we aim to validate these circular molecules in independent blood cohorts as well as in cerebrospinal fluid and plasma samples to fully elucidate whether these highly stable RNA molecules could be used as disease biomarkers.","PeriodicalId":318593,"journal":{"name":"D: Wet biomarkers","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132122260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D01 Two independent validations of a mutant huntingtin protein (MHTT) assay to support the clinical development of mHTT-targeting therapies in HD","authors":"D. Hawellek, S. Vauléon, Katharina Schutz, Benoit Massonnet, Nanda Gruben, M. Manchester, L. Boak, S. Schobel","doi":"10.1136/jnnp-2021-ehdn.32","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.32","url":null,"abstract":"Background Huntington’s disease (HD) is caused by a CAG repeat expansion in the huntingtin gene, resulting in the production of toxic mutant huntingtin protein (mHTT). Quantification of mHTT in the cerebrospinal fluid (CSF) of patients with HD using a method validated as per international guidelines is critical to support the clinical development of mHTT-targeting therapies. Aims To validate a bioanalytical method for quantifying relative mHTT levels in human CSF in two independent laboratories. Methods The assay was optimised in a single laboratory before its transfer to a second independent laboratory. All results were generated in regulated bioanalytical environments (i.e. by Good Clinical Practice-trained personnel in Good Laboratory Practice-certified laboratories) using a bead-based sandwich ligand-binding assay with Single Molecule Counting detection on the SMCxPROTM (Merck). The ultra-sensitive assay employs the antibody pair 2B7/MW1 for capture and detection and artificial CSF as a surrogate matrix. Assay validation followed international guidelines adapted to the context of use. Results Full assay validation performed in two independent laboratories (Roche, PRA Health Sciences) confirmed robust inter- and intra-assay accuracy and precision and a high sensitivity (lower limit of quantification =1.63 pg-eq/mL [Roche], 1.64 pg-eq/mL [PRA Health Sciences]). Parallelism and specificity experiments involving CSF from patients with HD as well as artificial CSF matrices confirmed the selectivity and specificity of the assay, and the absence of a matrix effect. Stability of mHTT in artificial CSF was found to be sufficient to accommodate bioanalysis. Conclusions The independent method validations demonstrate that this ultra-sensitive assay can be replicated and transferred, making it a reliable and broadly relevant tool for generating biomarker data in registrational clinical trials for mHTT-lowering therapies. Study sponsored by F. Hoffmann-La Roche Ltd.","PeriodicalId":318593,"journal":{"name":"D: Wet biomarkers","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131200439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D02 Cerebrospinal fluid amyloid beta and glial fibrillary acidic protein concentrations in huntington’s disease","authors":"Sara Korpela, J. Sundblom, H. Zetterberg, R. Constantinescu, P. Svenningsson, Martin Paucar Arce, V. Niemelä","doi":"10.1136/jnnp-2021-ehdn.33","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.33","url":null,"abstract":"","PeriodicalId":318593,"journal":{"name":"D: Wet biomarkers","volume":"190 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127534218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}