title: Challenges, solutions, and recommendations for Alzheimer's disease combination therapy.
abstract: Given the complex neuropathology Alzheimer's disease (AD), combination therapy may be necessary for effective treatment. However, scientific, pragmatic, regulatory, and business challenges need to be addressed before combination therapy for AD can become a reality. Leaders from academia and industry, along with a former member of the Food and Drug Administration and the Alzheimer's Association, have explored these challenges and here propose a strategy to facilitate proof-of-concept combination therapy trials in the near future. First, a more integrated understanding of the complex pathophysiology and progression of AD is needed to identify the appropriate pathways and the disease stage to target. Once drug candidates are identified, novel clinical trial designs and selection of appropriate outcome assessments will be needed to enable definition and evaluation of the appropriate dose and dosing regimen and determination of efficacy. Success in addressing this urgent problem will only be achieved through collaboration among multiple stakeholders.
authors.affiliation: Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA. Electronic address: jhendrix@alz.org.
authors.forename: James A
authors.initials: JA
authors.lastname: Hendrix
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Bateman
authors.affiliation: Janssen Research & Development, South San Francisco, CA, USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Duggan
authors.affiliation: Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.affiliation: Independent Science Writer, Elverson, PA, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Bain
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: DeMattos
authors.affiliation: Independent Consultant, San Diego, CA, USA.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Katz
authors.affiliation: F. Hoffmann-La Roche Ltd, Neuroscience, Basel, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ostrowitzki
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Siemers
authors.affiliation: Memory Disorders Unit, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors.forename: Reisa
authors.initials: R
authors.lastname: Sperling
authors.affiliation: Pfizer, Inc., Neuroscience Research Unit, Cambridge, MA.
authors.forename: Ottavio V
authors.initials: OV
authors.lastname: Vitolo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000008:administration & dosage; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans
chemical_list: D053829:Amyloid Precursor Protein Secretases