Objective: Lunasin, a soy peptide that reportedly alters histone acetylation in vitro, was associated with a single ALS reversal in the media. Following an ALSUntangled report, we sought to determine whether Lunasin altered histone acetylation and improved progression in people with ALS, and whether patient-centric trial design features might improve enrollment and retention. Methods: This single-center, year-long trial (NCT02709330) featured broad inclusion criteria, historical controls, primarily virtual data collection, and real-time results. Participants measured their own ALSFRS-R score, weight and perceived efficacy, and recorded these monthly on PatientsLikeMe. Blood tests at screening and month 1 assessed alterations in histone H3 and H4 acetylation. The protocol was published online, empowering patients outside the study to self-experiment. Results: Fifty participants enrolled in 5.5 months. Although this population had more advanced disease compared to other trials, retention and adherence were very high. There was no significant effect of Lunasin treatment on histone acetylation or disease progression. A cohort following our protocol outside the trial reported similar side effects and perceived effectiveness; however, their compliance with data entry was markedly lower. Conclusions: While Lunasin's lack of efficacy is disappointing, our novel trial design had the highest ALS trial enrollment rate ever recorded, with excellent retention and adherence. Low data density from patients who are self-experimenting outside a formal protocol casts doubt on the possibility of gathering useful information from unsupervised expanded access programs or "right to try" initiatives.
Objective: Lunasin, a soy peptide that reportedly alters histone acetylation in vitro, was associated with a single ALS reversal in the media. Following an ALSUntangled report, we sought to determine whether Lunasin altered histone acetylation and improved progression in people with ALS, and whether patient-centric trial design features might improve enrollment and retention. Methods: This single-center, year-long trial (NCT02709330) featured broad inclusion criteria, historical controls, primarily virtual data collection, and real-time results. Participants measured their own ALSFRS-R score, weight and perceived efficacy, and recorded these monthly on PatientsLikeMe. Blood tests at screening and month 1 assessed alterations in histone H3 and H4 acetylation. The protocol was published online, empowering patients outside the study to self-experiment. Results: Fifty participants enrolled in 5.5 months. Although this population had more advanced disease compared to other trials, retention and adherence were very high. There was no significant effect of Lunasin treatment on histone acetylation or disease progression. A cohort following our protocol outside the trial reported similar side effects and perceived effectiveness; however, their compliance with data entry was markedly lower. Conclusions: While Lunasin's lack of efficacy is disappointing, our novel trial design had the highest ALS trial enrollment rate ever recorded, with excellent retention and adherence. Low data density from patients who are self-experimenting outside a formal protocol casts doubt on the possibility of gathering useful information from unsupervised expanded access programs or "right to try" initiatives.
Authors: Walter H Moos; Douglas V Faller; Ioannis P Glavas; David N Harpp; Iphigenia Kanara; Anastasios N Mavrakis; Julie Pernokas; Mark Pernokas; Carl A Pinkert; Whitney R Powers; Konstantina Sampani; Kosta Steliou; Demetrios G Vavvas; Robert J Zamboni; Krishna Kodukula; Xiaohong Chen Journal: Biores Open Access Date: 2020-03-31
Authors: Matthew C Kiernan; Steve Vucic; Kevin Talbot; Christopher J McDermott; Orla Hardiman; Jeremy M Shefner; Ammar Al-Chalabi; William Huynh; Merit Cudkowicz; Paul Talman; Leonard H Van den Berg; Thanuja Dharmadasa; Paul Wicks; Claire Reilly; Martin R Turner Journal: Nat Rev Neurol Date: 2020-12-18 Impact factor: 42.937
Authors: Charis Wong; Maria Stavrou; Elizabeth Elliott; Jenna M Gregory; Nigel Leigh; Ashwin A Pinto; Timothy L Williams; Jeremy Chataway; Robert Swingler; Mahesh K B Parmar; Nigel Stallard; Christopher J Weir; Richard A Parker; Amina Chaouch; Hisham Hamdalla; John Ealing; George Gorrie; Ian Morrison; Callum Duncan; Peter Connelly; Francisco Javier Carod-Artal; Richard Davenport; Pablo Garcia Reitboeck; Aleksandar Radunovic; Venkataramanan Srinivasan; Jenny Preston; Arpan R Mehta; Danielle Leighton; Stella Glasmacher; Emily Beswick; Jill Williamson; Amy Stenson; Christine Weaver; Judith Newton; Dawn Lyle; Rachel Dakin; Malcolm Macleod; Suvankar Pal; Siddharthan Chandran Journal: Brain Commun Date: 2021-10-23