A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Autor: Salloway S; Warren Alpert Medical School of Brown University, Providence, RI, USA., Farlow M; Indiana University School of Medicine, Indianapolis, IN, USA., McDade E; Washington University School of Medicine, St. Louis, MO, USA., Clifford DB; Washington University School of Medicine, St. Louis, MO, USA., Wang G; Washington University School of Medicine, St. Louis, MO, USA., Llibre-Guerra JJ; Washington University School of Medicine, St. Louis, MO, USA., Hitchcock JM; Hitchcock Regulatory Consulting, Inc, Fishers, IN, USA., Mills SL; Washington University School of Medicine, St. Louis, MO, USA., Santacruz AM; Washington University School of Medicine, St. Louis, MO, USA., Aschenbrenner AJ; Washington University School of Medicine, St. Louis, MO, USA., Hassenstab J; Washington University School of Medicine, St. Louis, MO, USA., Benzinger TLS; Washington University School of Medicine, St. Louis, MO, USA., Gordon BA; Washington University School of Medicine, St. Louis, MO, USA., Fagan AM; Washington University School of Medicine, St. Louis, MO, USA., Coalier KA; Washington University School of Medicine, St. Louis, MO, USA., Cruchaga C; Washington University School of Medicine, St. Louis, MO, USA., Goate AA; Icahn School of Medicine at Mount Sinai, New York, NY, USA., Perrin RJ; Washington University School of Medicine, St. Louis, MO, USA., Xiong C; Washington University School of Medicine, St. Louis, MO, USA., Li Y; Washington University School of Medicine, St. Louis, MO, USA., Morris JC; Washington University School of Medicine, St. Louis, MO, USA., Snider BJ; Washington University School of Medicine, St. Louis, MO, USA., Mummery C; University College London, London, UK., Surti GM; Warren Alpert Medical School of Brown University, Providence, RI, USA., Hannequin D; Centre Hospitalier Universitaire de Rouen, Rouen, France., Wallon D; Centre Hospitalier Universitaire de Rouen, Rouen, France., Berman SB; University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Lah JJ; Emory University Medical Center, Atlanta, GA, USA., Jimenez-Velazquez IZ; University of Puerto Rico School of Medicine, San Juan, Puerto Rico., Roberson ED; University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA., van Dyck CH; Yale University School of Medicine, New Haven, CT, USA., Honig LS; Columbia University Medical Center, New York, NY, USA., Sánchez-Valle R; Hospital Clínic i Provincial de Barcelona, August Pi i Sunyer Biomedical Research Institute-Universitat de Barcelona, Barcelona, Spain., Brooks WS; Neuroscience Research Australia, University of New South Wales Medicine, Randwick, New South Wales, Australia., Gauthier S; McGill Center for Studies in Aging, McGill University, Montreal, Quebec, Canada., Galasko DR; University of California San Diego, San Diego, CA, USA., Masters CL; University of Melbourne, Melbourne, Victoria, Australia., Brosch JR; Indiana University School of Medicine, Indianapolis, IN, USA., Hsiung GR; University of British Columbia, Vancouver, British Columbia, Canada., Jayadev S; University of Washington School of Medicine, Seattle, WA, USA., Formaglio M; Hospices Civils de Lyon, Lyons, France., Masellis M; Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada., Clarnette R; Australian Alzheimer's Research Foundation, University of Western Australia, Perth, Western Australia, Australia., Pariente J; Centre Hospitalier Universitaire de Toulouse, Toulouse, France., Dubois B; Neurological Institute, Salpetriere University Hospital, Paris, France., Pasquier F; Centre Hospitalier Régional Universitaire de Lille, Lille, France., Jack CR Jr; Mayo Clinic, Rochester, MN, USA., Koeppe R; University of Michigan, Ann Arbor, MI, USA., Snyder PJ; University of Rhode Island, Kingston, RI, USA., Aisen PS; Keck School of Medicine, University of Southern California, San Diego, CA, USA., Thomas RG; University of California San Diego, San Diego, CA, USA., Berry SM; Berry Consultants, LLC, Austin, TX, USA., Wendelberger BA; Berry Consultants, LLC, Austin, TX, USA., Andersen SW; Eli Lilly and Company, Indianapolis, IN, USA., Holdridge KC; Eli Lilly and Company, Indianapolis, IN, USA., Mintun MA; Eli Lilly and Company, Indianapolis, IN, USA., Yaari R; Eli Lilly and Company, Indianapolis, IN, USA., Sims JR; Eli Lilly and Company, Indianapolis, IN, USA., Baudler M; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Delmar P; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Doody RS; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Fontoura P; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Giacobino C; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Kerchner GA; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Bateman RJ; Washington University School of Medicine, St. Louis, MO, USA. batemanr@wustl.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2021 Jul; Vol. 27 (7), pp. 1187-1196. Date of Electronic Publication: 2021 Jun 21.
DOI: 10.1038/s41591-021-01369-8
Abstrakt: Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation were assigned to receive gantenerumab, 52 solanezumab and 40 placebo. Both drugs engaged their Aβ targets but neither demonstrated a beneficial effect on cognitive measures compared to controls. The solanezumab-treated group showed a greater cognitive decline on some measures and did not show benefits on downstream biomarkers. Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. Amyloid-related imaging abnormalities edema was observed in 19.2% (3 out of 11 were mildly symptomatic) of the gantenerumab group, 2.5% of the placebo group and 0% of the solanezumab group. Gantenerumab and solanezumab did not slow cognitive decline in symptomatic DIAD. The asymptomatic groups showed no cognitive decline; symptomatic participants had declined before reaching the target doses.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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