Have there been improvements in Alzheimer's disease drug discovery over the past 5 years?

被引:53
作者
Cacabelos, Ramon [1 ,2 ]
机构
[1] EuroEspes Biomed Res Ctr, Inst Med Sci & Genom Med, Corunna, Spain
[2] Continental Univ, Chair Genom Med, Med Sch, Huancayo, Peru
关键词
Alzheimer's disease; treatment; pharmacological categories; anti-A beta treatments; anti-tau treatments; immunotherapy; natural products; novel targets; pharmacogenetics; A-BETA; GENE-THERAPY; CLINICAL-TRIALS; DOUBLE-BLIND; PHARMACOGENOMICS; SEMAGACESTAT; MEDICATIONS; SOLANEZUMAB; STRATEGIES; MODULATORS;
D O I
10.1080/17460441.2018.1457645
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Alzheimer's disease (AD) is the most important neurodegenerative disorder with a global cost worldwide of over $700 billion. Pharmacological treatment accounts for 10-20% of direct costs; no new drugs have been approved during the past 15 years; and the available medications are not cost-effective. Areas covered: A massive scrutiny of AD-related PubMed publications (ps)(2013-2017) identified 42,053ps of which 8,380 (19.60%) were associated with AD treatments. The most prevalent pharmacological categories included neurotransmitter enhancers (11.38%), multi-target drugs (2.45%), anti-Amyloid agents (13.30%), anti-Tau agents (2.03%), natural products and derivatives (25.58%), novel drugs (8.13%), novel targets (5.66%), other (old) drugs (11.77%), anti-inflammatory drugs (1.20%), neuroprotective peptides (1.25%), stem cell therapy (1.85%), nanocarriers/nanotherapeutics (1.52%), and others (<1% each). Expert opinion: Unsuccessful outcomes in AD therapeutics are attributed to pathogenic misconceptions, erratic procedures in drug development and inappropriate regulations. Recommendations for the future are as follows: (i) the reconsideration of dominant pathogenic theories, (ii) the identification of reliable biomarkers, (iii) the redefinition of diagnostic criteria, (iv) new guidelines for disease management, (v) the reorientation of drug discovery programs, (vi) the updating of regulatory requirements, (vii) the introduction of pharmacogenomics in drug development and personalized treatments, and (viii) the implementation of preventive programs.
引用
收藏
页码:523 / 538
页数:16
相关论文
共 80 条
[1]   Bapineuzumab for mild to moderate Alzheimer's disease: a meta-analysis of randomized controlled trials [J].
Abushouk, Abdelrahman Ibrahim ;
Elmaraezy, Ahmed ;
Aglan, Amro ;
Salama, Reham ;
Fouda, Samar ;
Fouda, Rana ;
AlSafadi, Ammar M. .
BMC NEUROLOGY, 2017, 17
[2]   Stem cell models of Alzheimer's disease: progress and challenges [J].
Arber, Charles ;
Lovejoy, Christopher ;
Wray, Selina .
ALZHEIMERS RESEARCH & THERAPY, 2017, 9
[3]   Peptides Acting as Cognitive Enhancers [J].
Asua, Diego ;
Bougamra, Ghassen ;
Calleja-Felipe, Maria ;
Morales, Miguel ;
Knafo, Shira .
NEUROSCIENCE, 2018, 370 :81-87
[4]   Brain-derived neurotrophic factor and its clinical implications [J].
Bathina, Siresha ;
Das, Undurti N. .
ARCHIVES OF MEDICAL SCIENCE, 2015, 11 (06) :1164-1178
[5]  
Britt Daniel M I, 2016, Mo Med, V113, P207
[6]   Utilizing Structures of CYP2D6 and BACE1 Complexes To Reduce Risk of Drug-Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors [J].
Brodney, Michael A. ;
Beck, Elizabeth M. ;
Butler, Christopher R. ;
Barreiro, Gabriela ;
Johnson, Eric F. ;
Riddell, David ;
Parris, Kevin ;
Nolan, Charles E. ;
Fan, Ying ;
Atchison, Kevin ;
Gonzales, Cathleen ;
Robshaw, Ashley E. ;
Doran, Shawn D. ;
Bundesmann, Mark W. ;
Buzon, Leanne ;
Dutra, Jason ;
Henegar, Kevin ;
LaChapelle, Erik ;
Hou, Xinjun ;
Rogers, Bruce N. ;
Pandit, Jayvardhan ;
Lira, Ricardo ;
Martinez-Alsina, Luis ;
Mikochik, Peter ;
Murray, John C. ;
Ogilvie, Kevin ;
Price, Loren ;
Sakya, Subas M. ;
Yu, Aijia ;
Zhang, Yong ;
O'Neill, Brian T. .
JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (07) :3223-3252
[7]  
Cacabelos R, 2016, J GENOMIC MED PHARMA, V1, P151
[8]   Pleiotropy and promiscuity in pharmacogenomics for the treatment of Alzheimer's disease and related risk factors [J].
Cacabelos, Ramon .
FUTURE NEUROLOGY, 2018, 13 (02) :71-86
[9]   Pharmacogenetics of Vascular Risk Factors in Alzheimer's Disease [J].
Cacabelos, Ramon ;
Meyyazhagan, Arun ;
Carril, Juan C. ;
Cacabelos, Pablo ;
Teijido, Oscar .
JOURNAL OF PERSONALIZED MEDICINE, 2018, 8 (01)
[10]   Pharmacogenetic considerations in the treatment of Alzheimer's disease [J].
Cacabelos, Ramon ;
Torrellas, Clara ;
Teijido, Oscar ;
Carlos Carril, Juan .
PHARMACOGENOMICS, 2016, 17 (09) :1041-1074