Beyond immunotherapy: new approaches for disease modifying treatments for early Alzheimer's disease.
Current pharmacological recommendations for the treatment of Alzheimer's disease (AD) include the cholinesterase inhibitors and the N-methyl-D-aspartate antagonist, memantine. However, these medications only manage symptoms of AD, and do not target Aβ plaques and neurofibrillary tangles. As such, there is a need to develop effective and safe disease modifying treatments that directly target AD pathology and alter the course of AD progression. Areas covered: This review evaluates ongoing phase 2 and 3 clinical trials, as well as those completed or published over the past five years. Studies for this review were obtained from clinicaltrials.gov, alzforum.org/therapeutics, and PubMed. Keywords and search criteria included: phase 2, or 3 trials related to Alzheimer's disease, mild cognitive impairment, amyloid-beta and tau. Immunotherapies for AD have not been included as this is beyond the scope of this review. Expert opinion: A substantial number of trials investigating disease modifying drugs in AD target amyloid-beta and tau pathology. However, many of these trials have relatively short treatment duration and do not include combined assessment of biomarkers and clinical outcomes. Future investigations are recommended to include biomarker assessments and clinical outcomes over a minimum treatment duration of 18 months in order to establish disease-modifying effects.
a Hurvitz Brain Sciences Program , Sunnybrook Research Institute , Toronto , ON , Canada.|b Department of Pharmacology and Toxicology , University of Toronto , Toronto , ON , Canada.
Myuri
M
Ruthirakuhan
a Hurvitz Brain Sciences Program , Sunnybrook Research Institute , Toronto , ON , Canada.|c Department of Psychiatry , Sunnybrook Health Sciences Centre , Toronto , ON , Canada.
Nathan
N
Herrmann
a Hurvitz Brain Sciences Program , Sunnybrook Research Institute , Toronto , ON , Canada.
Ivonne
I
Suridjan
a Hurvitz Brain Sciences Program , Sunnybrook Research Institute , Toronto , ON , Canada.
Eleenor H
EH
Abraham
a Hurvitz Brain Sciences Program , Sunnybrook Research Institute , Toronto , ON , Canada.
Ilan
I
Farber
a Hurvitz Brain Sciences Program , Sunnybrook Research Institute , Toronto , ON , Canada.|b Department of Pharmacology and Toxicology , University of Toronto , Toronto , ON , Canada.|c Department of Psychiatry , Sunnybrook Health Sciences Centre , Toronto , ON , Canada.
Krista L
KL
Lanctôt
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D008559:Memantine
Alzheimer’s disease; Phase 2; amyloid-beta; disease modifying; phase 3; tau