scholarly journals Do We Need Anti-Prion Compounds to Treat Alzheimer’s Disease?

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2237 ◽  
Author(s):  
Dieter Willbold ◽  
Janine Kutzsche
Keyword(s):  
Alzheimer’S Disease ◽  
Clinical Trials ◽  
Clinical Efficacy ◽  
Etiologic Agent ◽  
Phase Iii ◽  
Current Phase ◽  
Drug Candidate ◽  
Efficacy Data ◽  
Drug Candidates ◽  
Phase Iii Clinical Trials

Background: While phase III clinical trials for the treatment of Alzheimer’s disease (AD) keep failing regardless of the target, more and more data suggest that the toxic protein assemblies of amyloid-beta protein (Aβ) and tubulin binding protein (TAU) behave like prions. Irrespective of the question of whether AD is theoretically or practically contagious, the presence of a self-replicating toxic etiologic agent in the brains of AD patients must have decisive consequences for drug development programs and clinical trial designs. Objectives: We intend to challenge the hypothesis that the underlying etiologic agent of AD is behaving prion-like. We want to discuss whether the outcome of clinical trials could have been predicted based on this hypothesis, and whether compounds that directly disassemble the toxic prion could be more beneficial for AD treatment. Method: We collected publicly accessible pre-clinical efficacy data of Aβ targeting compounds that failed or still are in phase III clinical trials. We describe the desired properties of an anti-prion compound and compare it the properties of past and current phase III drug candidates. Results: We could not find convincing and reproducible pre-clinical efficacy data of past and current phase III drug candidates on cognition other than in preventive treatment settings. The desired properties of an anti-Aβ-prionic compound are fulfilled by the drug candidate RD2, which has been developed to directly disassemble toxic Aβ oligomers. Conclusion: RD2 is the first anti-prion drug candidate. It is able to enhance cognition and impede neurodegeneration in three different transgenic AD mouse models, even under truly non-preventive conditions and even when applied orally. In addition, it is safe in humans.

Novel approaches to incorporating pharmacoeconomic studies into phase III clinical trials for Alzheimer's disease

2010 ◽  
Vol 14 (8) ◽  
pp. 640-647 ◽  
Author(s):  
H. Fillit ◽  
J. Cummings ◽  
P. Neumann ◽  
T. Mclaughlin ◽  
P. Salavtore ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Novel Approaches

scholarly journals New Approacher in the Development of Alzheimer’s Disease Modifying Drugs

2021 ◽  
pp. 88
Author(s):  
◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Tau Protein ◽  
Phase Iii ◽  
Disease Modifying Drugs ◽  
Phase Iii Clinical Trials ◽  
Research Level ◽  
Disease Modifying ◽  
Pathological Stages

Introduction: Alzheimer’s disease is a more common neurodegenerative disease, affecting 25 million people worldwide, or accounting for about 60 to 70% of all dementia cases. There is currently no exact mechanism to explain the pathophysiology of Alzheimer’s disease, however, cascading metabolic amyloid and post-translational review of tau protein are used as major hypotheses. Objective: To demonstrate in the literature new approaches in the development of Alzheimer’s disease modifiers. Methodology: For the accomplishment of this study made in the bibliographical survey of scientific literature and respect to the approached subject, in the databases PUBMED, ScienceDirect, Scielo and Scopus. Results: Alzheimer’s disease-modifying drugs are not yet available, but many patients may, however, develop phase III clinical trials and are intended to modify as pathological stages leading to the disease. As disease-modifying therapies under study, these changes also affect Aβ and tau protein and also cause inflammation and oxidative damage. The results obtained in the clinical trials performed were positive and promising and are still under study. The results show that there is still a long way to go in the development of Alzheimer’s disease modifying drugs. Conclusion: The results demonstrated that there is still a long way to go in the development of Alzheimer’s disease modifying drugs, but nevertheless levels at the research level should be continued in order to improve the pathophysiology of the disease and find an effective treatment for this disease the same.

scholarly journals Toolbox: Current phase III clinical trials

2012 ◽  
Vol 2 (6) ◽  
pp. 138-138
Author(s):  
Tiffany-Jade Kreys
Keyword(s):  
Clinical Trials ◽  
Phase Iii ◽  
Current Phase ◽  
Phase Iii Clinical Trials

scholarly journals Ustekinumab in psoriatic arthritis and related phenotypes

2018 ◽  
Vol 9 (10) ◽  
pp. 191-198 ◽  
Author(s):  
Isobel Dobbin-Sears ◽  
Janet Roberts ◽  
Darren D. O’Rielly ◽  
Proton Rahman
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Clinical Efficacy ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Clinical Trials ◽  
Th 17 ◽  
Inflammatory Bowel ◽  
Inflammatory Drugs

Psoriatic arthritis (PsA) is an inflammatory arthritis that commonly occurs with psoriasis and is attributed to genetic, immunologic and environmental factors. The T-helper (Th)-17 pathway and the interleukin (IL)-23/IL-17 axis have become prominent players in PsA and considerably increased our understanding of disease pathogenesis. In this review article, we will focus on the emerging role of IL-12/23 and its blockade, in the pathogenesis and management of PsA as well as of psoriasis and inflammatory bowel disease. Ustekinumab, is a fully human monoclonal immunoglobulin (Ig)G1 antibody that binds specifically to the p40 subunit of IL-12 and IL-23, primarily inhibiting downstream Th-17 signalling pathways. Ustekinumab produced consistent and sustained clinical efficacy in two phase III clinical trials in PsA, PSUMMIT-1 and PSUMMIT-2, with data out to 52 weeks, and no new safety signals. PSUMMIT-1 included patients with active PsA despite conventional therapy who were all naïve to anti-tumour necrosis factor (TNF) agents, whereas PSUMMIT-2 also included anti-TNF experienced patients. Similarly, ustekinumab produced consistent clinical efficacy in two phase III clinical trials in psoriasis, PHOENIX-1 and PHOENIX-2, and in both induction and maintenance of moderate-to-severe Crohn’s disease, UNITI-1, UNITI-2 and IM-UNITI, without an increased safety signal. Currently, ustekinumab is used in the treatment of PsA following the failure of nonsteroidal anti-inflammatory drugs (NSAIDs) and conventional disease-modifying antirheumatic drugs (DMARDs), and as an alternative to, or after failure of an anti-TNF agent.

scholarly journals Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer’s Disease Patients

2017 ◽  
Vol 57 (2) ◽  
pp. 557-573 ◽  
Author(s):  
Nzeera Ketter ◽  
H. Robert Brashear ◽  
Jennifer Bogert ◽  
Jianing Di ◽  
Yves Miaux ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Clinical Trials

Amyloid Beta Hypothesis in Alzheimer's Disease: Major Culprits and Recent Therapeutic Strategies

2020 ◽  
Vol 21 (2) ◽  
pp. 148-166 ◽  
Author(s):  
Dileep Vijayan ◽  
Remya Chandra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Amyloid Beta ◽  
Phase Iii ◽  
Aβ Peptides ◽  
Amyloid Hypothesis ◽  
Phase Iii Clinical Trials ◽  
Functional Aspects

Alzheimer’s disease (AD) is one of the most common forms of dementia and has been a global concern for several years. Due to the multi-factorial nature of the disease, AD has become irreversible, fatal and imposes a tremendous socio-economic burden. Even though experimental medicines suggested moderate benefits, AD still lacks an effective treatment strategy for the management of symptoms or cure. Among the various hypotheses that describe development and progression of AD, the amyloid hypothesis has been a long-term adherent to the AD due to the involvement of various forms of Amyloid beta (Aβ) peptides in the impairment of neuronal and cognitive functions. Hence, majority of the drug discovery approaches in the past have focused on the prevention of the accumulation of Aβ peptides. Currently, there are several agents in the phase III clinical trials that target Aβ or the various macromolecules triggering Aβ deposition. In this review, we present the state of the art knowledge on the functional aspects of the key players involved in the amyloid hypothesis. Furthermore, we also discuss anti-amyloid agents present in the Phase III clinical trials.

scholarly journals Current Trends in the Development of Drugs for the Treatment of Alzheimer’s Disease and their Clinical Trials

2018 ◽  
Vol 1 (3) ◽  
pp. e00015 ◽  
Author(s):  
S.O. Bachurin ◽  
E.V. Bovina ◽  
A.A. Ustyugov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Neuronal Loss ◽  
Phase Iii ◽  
Molecular Pathways ◽  
Drug Candidates ◽  
Neurodegenerative Process ◽  
Thomson Reuters ◽  
Disease Modifying Agents

Intracellular and extracellular accumulation of fibrillary proteins, beta-amyloid and hyperphosphorylated Tau, in patients with Alzheimer’s disease (AD) leads to chronic and progressive neurodegenerative process. Overaccumulation of aggregates results in synaptic dysfunction and inevitable neuronal loss. Although the exact molecular pathways of the AD still require better understanding, it is clear this neuropathology is a multifactorial disorder where the advanced age is the main risk factor. Lately, several dozens of drug candidates have succeeded to phase II clinical trials; however, none has passed phase III. In this review we summarize existing data on anti-AD therapeutic agents currently undergoing clinical trials and included in the public websites www.clinicaltrials.gov and Alzforum.org as well as the Thomson Reuters «Integrity» database. We revealed three major trends in AD drug discovery. First, developing of “disease-modifying agents” could potentially slow the progression of structural and functional abnormalities in the central nervous system providing sustainable improvements of cognitive functions, which persist even after drug withdrawal. Secondly, the focused design of multitargeted drugs acting on multiple key molecular pathways. Finally, the repositioning of drugs that are already available on the market for the novel (anti-AD) application provides a promising strategy for finishing clinical trials and re-marketing.

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