التفاصيل البيبلوغرافية
| العنوان: |
Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. |
| المؤلفون: |
Wilson, Katherine M, Katona, Eszter, Knowles, Kathryn, Lebouvier, Thibaud, Leitão, Maria João, Levin, Johannes, Lladó, Albert, Lombardi, Gemma, Lombardi, Jolina, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Miltenberger, Gabriel, Patil, Saurabh, Minkelen, Rick van, Mitchell, Sara, Moreno, Fermin, Nacmias, Benedetta, Nelson, Annabel, Nicholas, Jennifer, Öijerstedt, Linn, Papma, Janne M, Pasquier, Florence, Peakman, Georgia, Mohapatra, Susovan, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Liu, Yuanjing, Rossi, Giacomina, Rossor, Martin, Santana, Isabel, Santiago, Beatriz, Saracino, Dario, Scarpini, Elio, Schönecker, Sonja, Shafei, Rachelle, Shoesmith, Christen, Sorbi, Sandro, Goyal, Jaya, Tábuas-Pereira, Miguel, Tagliavini, Fabrizio, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Sanchez-Valle, Raquel, Damme, Philip Van, Vandenbulcke, Mathieu, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Wlasich, Elisabeth, Zulaica, Miren, Laforce, Robert Jr, Synofzik, Matthis, Rowe, James B, Finger, Elizabeth, Glaria, Idoia, Vandenberghe, Rik, Butler, Christopher R, Gerhard, Alexander, Van Swieten, John C, Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, de Mendonça, Alexandre, Masellis, Mario, Tartaglia, M Carmela, Carcolé, Mireia, Otto, Markus, Graff, Caroline, Ducharme, Simon, Schott, Jonathan M, Malaspina, Andrea, Zetterberg, Henrik, Boyanapalli, Ramakrishna, Rohrer, Jonathan D, Isaacs, Adrian M, Initiative, Genetic FTD, Swift, Imogen J, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Sogorb-Esteve, Aitana, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Heller, Carolin, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Convery, Rhian, Bouzigues, Arabella, Cope, Thomas, Danek, Adrian, Deramecourt, Vincent, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Heslegrave, Amanda J, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Graf, Lisa, Keshavan, Ashvini, Greaves, Caroline, Guerreiro, Rita, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Ber, Isabelle Le |
| المصدر: |
Journal of neurology, neurosurgery, and psychiatry 93(7), 761-771 (2022). doi:10.1136/jnnp-2021-328710 |
| بيانات النشر: |
BMJ Publishing Group |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
info:eu-repo/classification/ddc/610, Amyotrophic Lateral Sclerosis: cerebrospinal fluid, Amyotrophic Lateral Sclerosis: diagnosis, Amyotrophic Lateral Sclerosis: genetics, Biomarkers: cerebrospinal fluid, C9orf72 Protein: genetics, DNA Repeat Expansion: genetics, Frontotemporal Dementia: diagnosis, Frontotemporal Dementia: genetics, Frontotemporal Dementia: metabolism, Humans, FRONTOTEMPORAL DEMENTIA, MOTOR NEURON DISEASE |
| جغرافية الموضوع: |
DE |
| الوصف: |
A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay.We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS.We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
info:eu-repo/semantics/altIdentifier/issn/2753-0485; info:eu-repo/semantics/altIdentifier/issn/2753-0477; info:eu-repo/semantics/altIdentifier/issn/0368-329X; info:eu-repo/semantics/altIdentifier/issn/0266-8637; info:eu-repo/semantics/altIdentifier/pmid/pmid:35379698; info:eu-repo/semantics/altIdentifier/issn/1468-330X; info:eu-repo/semantics/altIdentifier/issn/0022-3050; https://pub.dzne.de/record/163953Test; https://pub.dzne.de/search?p=id:%22DZNE-2022-00627%22Test |
| الإتاحة: |
https://doi.org/10.1136/jnnp-2021-328710Test
https://pub.dzne.de/record/163953Test
https://pub.dzne.de/search?p=id:%22DZNE-2022-00627%22Test |
| حقوق: |
info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.7C9ACD4C |
| قاعدة البيانات: |
BASE |
