Authors
Tania F Gendron, Jeannie Chew, Jeannette N Stankowski, Lindsey R Hayes, Yong-Jie Zhang, Mercedes Prudencio, Yari Carlomagno, Lillian M Daughrity, Karen Jansen-West, Emilie A Perkerson, Aliesha O’Raw, Casey Cook, Luc Pregent, Veronique Belzil, Marka Van Blitterswijk, Lilia J Tabassian, Chris W Lee, Mei Yue, Jimei Tong, Yuping Song, Monica Castanedes-Casey, Linda Rousseau, Virginia Phillips, Dennis W Dickson, Rosa Rademakers, John D Fryer, Beth K Rush, Otto Pedraza, Ana M Caputo, Pamela Desaro, Carla Palmucci, Amelia Robertson, Michael G Heckman, Nancy N Diehl, Edythe Wiggs, Michael Tierney, Laura Braun, Jennifer Farren, David Lacomis, Shafeeq Ladha, Christina N Fournier, Leo F McCluskey, Lauren B Elman, Jon B Toledo, Jennifer D McBride, Cinzia Tiloca, Claudia Morelli, Barbara Poletti, Federica Solca, Alessandro Prelle, Joanne Wuu, Jennifer Jockel-Balsarotti, Frank Rigo, Christine Ambrose, Abhishek Datta, Weixing Yang, Denitza Raitcheva, Giovanna Antognetti, Alexander McCampbell, John C Van Swieten, Bruce L Miller, Adam L Boxer, Robert H Brown, Robert Bowser, Timothy M Miller, John Q Trojanowski, Murray Grossman, James D Berry, William T Hu, Antonia Ratti, Bryan J Traynor, Matthew D Disney, Michael Benatar, Vincenzo Silani, Jonathan D Glass, Mary Kay Floeter, Jeffrey D Rothstein, Kevin B Boylan, Leonard Petrucelli
Publication date
2017/3/29
Journal
Science translational medicine
Volume
9
Issue
383
Pages
eaai7866
Publisher
American Association for the Advancement of Science
Description
There is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease. However, discovery of a G4C2 repeat expansion in the C9ORF72 gene as the most common genetic cause of ALS has opened up new avenues for therapeutic intervention for this form of ALS. G4C2 repeat expansion RNAs and proteins of repeating dipeptides synthesized from these transcripts are believed to play a key role in C9ORF72-associated ALS (c9ALS). Therapeutics that target G4C2 RNA, such as antisense oligonucleotides (ASOs) and small molecules, are thus being actively investigated. A limitation in moving such treatments from bench to bedside is a lack of pharmacodynamic markers for use in clinical trials. We explored whether poly(GP) proteins translated from G4C2 RNA could serve such a purpose. Poly(GP) proteins were detected in cerebrospinal fluid (CSF) and in peripheral blood …
Scholar articles
TF Gendron, J Chew, JN Stankowski, LR Hayes… - Science translational medicine, 2017