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A National Spinal Muscular Atrophy Registry for Real-World Evidence
- Victoria L. Hodgkinson, Maryam Oskoui, Joshua Lounsberry, Saïd M’Dahoma, Emily Butler, Craig Campbell, Alex MacKenzie, Hugh J. McMillan, Louise Simard, Jiri Vajsar, Bernard Brais, Kristine M. Chapman, Nicolas Chrestian, Meghan Crone, Peter Dobrowolski, Susan Dojeiji, James J. Dowling, Nicolas Dupré, Angela Genge, Hernan Gonorazky, Simona Hasal, Aaron Izenberg, Wendy Johnston, Edward Leung, Hanns Lochmüller, Jean K. Mah, Alier Marerro, Rami Massie, Laura McAdam, Anna McCormick, Michel Melanson, Michelle M. Mezei, Cam-Tu E. Nguyen, Colleen O’Connell, Erin K. O’Ferrall, Gerald Pfeffer, Cecile Phan, Stephanie Plamondon, Chantal Poulin, Xavier Rodrigue, Kerri L. Schellenberg, Kathy Selby, Jordan Sheriko, Christen Shoesmith, Garth Smith, Monique Taillon, Sean Taylor, Jodi Warman Chardon, Scott Worley, Lawrence Korngut
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 47 / Issue 6 / November 2020
- Published online by Cambridge University Press:
- 04 June 2020, pp. 810-815
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- Article
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Background:
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
Methods:The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
Results:The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Conclusion:Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Gene expression analysis of bovine embryonic disc, trophoblast and parietal hypoblast at the start of gastrulation
- Peter L. Pfeffer, Craig S. Smith, Paul Maclean, Debra K. Berg
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In cattle early gastrulation-stage embryos (Stage 5), four tissues can be discerned: (i) the top layer of the embryonic disc consisting of embryonic ectoderm (EmE); (ii) the bottom layer of the disc consisting of mesoderm, endoderm and visceral hypoblast (MEH); (iii) the trophoblast (TB); and (iv) the parietal hypoblast. We performed microsurgery followed by RNA-seq to analyse the transcriptome of these four tissues as well as a developmentally earlier pre-gastrulation embryonic disc. The cattle EmE transcriptome was similar at Stages 4 and 5, characterised by the OCT4/SOX2/NANOG pluripotency network. Expression of genes associated with primordial germ cells suggest their presence in the EmE tissue at these stages. Anterior visceral hypoblast genes were transcribed in the Stage 4 disc, but no longer by Stage 5. The Stage 5 MEH layer was equally similar to mouse embryonic and extraembryonic visceral endoderm. Our data suggest that the first mesoderm to invaginate in cattle embryos is fated to become extraembryonic. TGFβ, FGF, VEGF, PDGFA, IGF2, IHH and WNT signals and receptors were expressed, however the representative members of the FGF families differed from that seen in equivalent tissues of mouse embryos. The TB transcriptome was unique and differed significantly from that of mice. FGF signalling in the TB may be autocrine with both FGFR2 and FGF2 expressed. Our data revealed a range of potential inter-tissue interactions, highlighted significant differences in early development between mice and cattle and yielded insight into the developmental events occurring at the start of gastrulation.
Contributors
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- By Dag Aarsland, Adrià Arboix, Carlos Bazán, James T. Becker, Sylvie Belleville, Kevin M. Biglan, Sandra E. Black, Mariana Blanco, Rémi W. Bouchard, Bruce J. Brew, David J. Burn, Leonardo Caixeta, Richard Camicioli, Paulo Caramelli, Neil Cashman, Nicholas W. S. Davies, Yan Deschaintre, Rachel S. Doody, Bruno Dubois, Uwe Ehrt, Stephane Epelbaum, Ryan V. V. Evans, Joseph M. Ferrara, Bruno Franchi, Morris Freedman, Anders Gade, Serge Gauthier, Marta Grau-Olivares, Matthew E. Growdon, Will Guest, Marie Christie Guiot, Shahul Hameed, Mirna Lie Hosogi-Senaha, Ging-Yuek Robin Hsiung, Masamichi Ikawa, Rajive Jassal, Vesna Jelic, Peter Johannsen, Edward S. Johnson, Mary M. Kenan, Bert-Jan Kerklaan, Benjamin Lam, Gabriel C. Léger, Gabriel Leonard, Emilie Lepage, Irene Litvan, Oscar L. Lopez, Ian R. A. Mackenzie, Mario Masellis, Fodi Massoud, Paige Moorhouse, John C. Morris, Taim Muayqil, Yannick Nadeau, Inger Nennesmo, Jørgen E. Nielsen, Ricardo Nitrini, Sven-Eric Pålhagen, Robert Perry, Gerald Pfeffer, Machiel Pleizier, Steffen Plickert, Gil D. Rabinovici, Philippe H. Robert, Lothar Resch, Gustavo C. Román, Maxime Ros, Pedro Rosa-Neto, Aiman Sanosi, Philip Scheltens, Christian Schmidt, Eric Schmidt, Jean-Paul Soucy, Jette Stokholm, David Summers, Rawan Tarawneh, Louis Verret, Huali Wang, Bengt Winblad, Makoto Yoneda, Xin Yu, Inga Zerr
- Edited by Serge Gauthier, McGill University, Montréal, Pedro Rosa-Neto, McGill University, Montréal
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- Book:
- Case Studies in Dementia
- Published online:
- 16 May 2011
- Print publication:
- 21 April 2011, pp viii-xiv
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