Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer's disease patients.
Currently available drugs against Alzheimer's disease (AD) target cholinergic and glutamatergic neurotransmissions without affecting the underlying disease process. Putative disease-modifying drugs are in development and target β-amyloid (Aβ) peptide and tau protein, the principal neurophatological hallmarks of the disease. Areas covered: Phase III clinical studies of emerging anti-Aβ drugs for the treatment of AD were searched in US and EU clinical trial registries and in the medical literature until May 2016. Expert opinion: Drugs in Phase III clinical development for AD include one inhibitor of the β-secretase cleaving enzyme (BACE) (verubecestat), three anti-Aβ monoclonal antibodies (solanezumab, gantenerumab, and aducanumab), an inhibitor of receptor for advanced glycation end products (RAGE) (azeliragon) and the combination of cromolyn sodium and ibuprofen (ALZT-OP1). These drugs are mainly being tested in subjects during early phases of AD or in subjects at preclinical stage of familial AD or even in asymptomatic subjects at high risk of developing AD. The hope is to intervene in the disease process when it is not too late. However, previous clinical failures with anti-Aβ drugs and the lack of fully understanding of the pathophysiological role of Aβ in the development of AD, put the new drugs at substantial risk of failure.
a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.|b Unit of Neurodegenerative Disease, Department of Clinical Research in Neurology , University of Bari 'Aldo Moro' at 'Pia Fondazione Card. G. Panico' , Lecce , Italy.|c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo , Foggia , Italy.
Francesco
F
Panza
c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo , Foggia , Italy.
Davide
D
Seripa
d Geriatric Medicine-Memory Unit and Rare Disease Centre , University of Bari 'Aldo Moro' , Bari , Italy.
Vincenzo
V
Solfrizzi
e Research & Development Department , Chiesi Farmaceutici , Parma , Italy.
Bruno P
BP
Imbimbo
a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.
Madia
M
Lozupone
a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.
Antonio
A
Leo
f Biomedical Engineering Unit, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.
Rodolfo
R
Sardone
a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.
Gaetano
G
Gagliardi
g Psychiatric Unit, Department of Basic Medical Science, Neuroscience and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.
Lucia
L
Lofano
h Institute of Biochemistry and Clinical Biochemistry , Catholic University of Sacred Heart , Rome , Italy.
Bianca C
BC
Creanza
c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo , Foggia , Italy.
Paola
P
Bisceglia
i Institute of Neurology , Catholic University of Sacred Heart , Rome , Italy.
Antonio
A
Daniele
j Department of Clinical and Experimental Medicine , University of Foggia , Foggia , Italy.
Antonello
A
Bellomo
c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo , Foggia , Italy.
Antonio
A
Greco
a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.|b Unit of Neurodegenerative Disease, Department of Clinical Research in Neurology , University of Bari 'Aldo Moro' at 'Pia Fondazione Card. G. Panico' , Lecce , Italy.
Giancarlo
G
Logroscino
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D003499:Cyclic S-Oxides / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors; D013829:Thiadiazines / Q000494:pharmacology / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D003499:Cyclic S-Oxides; D004791:Enzyme Inhibitors; D000067759:Receptor for Advanced Glycation End Products; D013829:Thiadiazines; C000613570:verubecestat
ALZT-OP1; Alzheimer’s disease; BACE inhibitors; Monoclonal antibodies; aducanumab; azeliragon; cognitive disorders; dementia; gantenerumab; solanezumab; verubecestat