CNM-Au8 in Amyotrophic Lateral Sclerosis

作者：Douglas Hayden, Po-Ying Lai, Rachel Donahue, H. Chen, Jianing Wang, N. M. Mathai, Gabriela Lopes, Alexandra McCaffrey, Jennifer Scalia, Sarah Luppino, Clotilde Lagier‐Tourenne, Ghazaleh Sadri‐Vakili, Stephen J. Kolb, Sarah Heintzman, Robert Sufit, April Szymanski, Liberty Jenkins, A. D. Martin, Ericka Greene, Jason R. Thonhoff, Bing Liao, Charles H. Whitaker, Lora Clawson, Alpa Uchil, Kristen M. Riley, JinAe Arneklev, James Grogan, Xiaowei Su, Mansoureh Mamarabadi, Amber Malcolm, Tracy Bazan, Nassim Rad, Leo H. Wang, Eva L. Feldman, Ezequiel Piccione, Pariwat Thaisetthawatkul, Constantine Farmakidis, Duaa Jabari, Jeffrey Statland, Mamatha Pasnoor, Mazen M. Dimachkie, Robert H. Brown, Mehdi Ghasemi, Hajar Houmani, Catherine Douthwright, Kate Daniello, Niraja Suresh, Jerrica Farias, I-Hweii A. Chen, Piera Pasinelli, Kara Steijlen, Ratna Bhavaraju‐Sanka, Bill Jacobsen, Jourdan Milliard, Robert Bowser, Anahita Deboo, Michael S. Cartwright, Christopher Nance, Ludwig Gutmann, Julia Yasek, Matthew Harms, Matthew Burford, Frank Diaz, David Shrilla, Goran Rakočević, Sarah Jones, Guillermo Solórzano, Xiaoyan Li, Zabeen Mahuwala, Vishakhadatta Mathur Kumaraswamy, Colin Quinn, Michael Baer, David Borg, Karthikeyan Bhuvaneswaran, Jasdeep Kaur, Sam Maiser, Seward B. Rutkove, Andrew Mundwiler, Jenny Meyer, Pooja Rao, Raymond P. Roos, Ali A. Habib, Tahseen Mozaffar, Manisha Kak Korb, Jeffrey D. Mullen, Nathaniel M. Robbins, Nathan Carberry, Volkan Granit, Raghav Govindarajan, Christina Fournier, Björn Oskarsson, Leila Darki, Rodrigo Rodriguez, Miguel Chuguilin, Whitney McNeely, Montserrat Diaz‐Abad, Peter H. Jin, Chandana Chauhan, James Bobenhouse, N. Staff, Ghazala Hayat, Luisa Arroyave, Abbey Bailey, Jesse Bailey, Victoria Barlow, Allison Bulat, Genevive Changkuon, Melissa Cirino, Cristina Deignan, Emma Deirmendjian, Annette De Mattos, Sofia DiStefano, Kristin Drake, M L Estes, Kenneth Faulconer, Precious Figueroa-Szostek, Tessa Garozzo, Meredith Gibbons Hasenoehrl, Jennifer Henrique, Natalie Henrique, Samuel Hurwitz, Courtney Igne, L. R. Irwin, Katie Jentoft, Boglarka Jordan, Igor Katsovskiy, Olga Kharakozova, Taylor Kolvek, Alexander Korin, Thuong La, Haining Li, Joey Nguyen, Ilya Novak, Ricardo Ortiz, Joe Ostrow, Jaclyn Pagliaro, Jack Palillo, Payal Patel, Janae Patterson, Minh Phan, Najla Popel, Serena Proueng, Jesse Rosenthal, Catherine B. Small, Natalia Tarasenko, Mirna Thomas, Prasha Vigneswaran, Yusra Wahab, Isaac Whitworth, Spencer Wright, Mariah Connolly, Diana De Santiago, Adrián Félix, Karly Garrett, Jenny Hamilton, Kamran Khan, Marlee Lovett, Linda S. Nelson, M. Vargas Pabón, Diana Rede, Patrick Bolger, Ahmed Fetouh, Joan Woodcook, Cornelia Kamp, Julie Kennedy, Andrew McGarry, Margherita Torti, James D. Berry, Nicholas J. Maragakis, Eric A. Macklin, Lori B. Chibnik, Melanie Quintana, Benjamin R. Saville, Michelle A. Detry, Matteo Vestrucci, Joseph Marion, Anna McGlothlin, Elijah W. Stommel, Marianne Chase, Lindsay Pothier, Brittney Harkey, Hong Yu, Alex Sherman, Jeremy M. Shefner, Meghan Hall, Gale Kittle, Suma Babu, Jinsy Andrews, Derek D’Agostino, Eric Tustison, Erica Scirocco, Elisa Giacomelli, Gustavo Alameda, Eduardo Locatelli, Doreen Ho, Adam Quick, Senda Ajroud‐Driss, Jonathan Katz, Daragh Heitzman, Stanley H. Appel, Sheetal Shroff, Kevin J. Felice, Zachary Simmons, Timothy M. Miller, Nicholas Olney, Michael D. Weiss, Stephen A. Goutman, Joseph Americo Fernandes, Omar Jawdat, Margaret Owegi, Laura A. Foster, Tuan Vu, Hristelina Ilieva, Daniel S. Newman, Ximena Arcila-Londono, Carlayne E. Jackson, Shafeeq Ladha, Terry Heiman‐Patterson, James B. Caress, Andrea Swenson, Amanda Peltier, Richard A. Lewis, Dominic Fee, Matthew Elliott, Richard Bedlack, Edward J. Kasarskis, Lauren Elman, Jeffrey V. Rosenfeld, David Walk, Courtney McIlduff, Paul Twydell, Eufrosina Young, Kristin Johnson, Kourosh Rezania, Namita Goyal, Jeffrey A. Cohen, Michael Benatar, Vovanti Jones, Jonathan D. Glass, Jaimin Shah, Said R. Beydoun, James Wymer, Lindsay Zilliox, Shakti Nayar, Gary L. Pattee, Jennifer M. Martinez‐Thompson, Austin Rynders, Jacob Evan, Jeremy Evan, Alan Hartford, Marjan Sepassi, Karen S. Ho, Robert Glanzman, Benjamin Greenberg, Michael T. Hotchkin, Sabrina Paganoni, Merit Cudkowicz, HEALEY ALS Platform Trial Study Group · 发表于：JAMA · 年份：2025 · DOI：10.1001/jama.2024.27643 · 被引用次数：14 · 研究领域：Amyotrophic Lateral Sclerosis Research、Neurogenetic and Muscular Disorders Research、Cervical and Thoracic Myelopathy

Importance: Bioenergetic failure has been proposed as a driver of amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of gold nanocrystals that catalyzes the conversion of nicotinamide adenine dinucleotide hydride into NAD+, resulting in an increase of cellular adenosine triphosphate production. Objective: To determine the effects of CNM-Au8 on ALS disease progression. Design, Setting, and Participants: CNM-Au8 was tested as a regimen of the HEALEY ALS Platform Trial, a phase 2/3, multicenter, randomized, double-blind platform trial. The study was conducted at 54 sites in the US from July 2020 to March 2022 (final follow-up, March 17, 2022). A total of 161 participants with ALS were randomized to receive CNM-Au8 (n = 120) or regimen-specific placebo (n = 41). Data from 123 concurrently randomized placebo participants in other regimens were combined for analyses. Interventions: Eligible participants were randomized in a 3:3:2 ratio to receive CNM-Au8 60 mg daily (n = 61), CNM-Au8 30 mg daily (n = 59), or matching placebo (n = 41) for 24 weeks. Main Outcomes and Measures: The primary efficacy outcome was change from baseline through week 24 in ALS disease severity measured by a bayesian shared parameter model of function (based on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) and survival, which provided an estimate of the rate of disease progression measured by the disease rate ratio (DRR), with a DRR of less than 1 indicating treatment benefit. S...