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.

Alzheimer’s Disease and other Tauopathies: Exploring Efficacy of Medicinal Plant-Derived Compounds in Alleviating Tau-Mediated Neurodegeneration

2021 ◽  
Vol 14 ◽  
Author(s):  
Siva Sundara Kumar Durairajan ◽  
Karthikeyan Selvarasu ◽  
Minu Rani Bera ◽  
Kaushik Rajaram ◽  
Ashok Iyaswamy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medicinal Plant ◽  
Tau Protein ◽  
Amyloid Β ◽  
Corticobasal Degeneration ◽  
Phase Iii ◽  
Disease Modifying Drugs ◽  
Stabilizing Agents ◽  
Phase Iii Clinical Trials

: Alzheimer’s disease (AD), a major form of dementia, has been reported to affect more than 50 million people worldwide. It is characterized by the presence of amyloid-β (Aβ) plaques and hyperphosphorylated Tau-associated neurofibrillary tangles in the brain. Apart from AD, microtubule (MT)-associated protein Tau is also involved in other neurodegenerative diseases called tauopathies, including Pick’s disease, frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration. The recently unsuccessful phase III clinical trials related to Aβ-targeted therapeutic drugs indicated that alternative targets, such as Tau, should be studied to discover more effective and safer drugs. Recent drug discovery approaches to reduce AD-related Tau pathologies are primarily based on blocking Tau aggregation, inhibiting Tau phosphorylation, compensating impaired Tau function with MT-stabilizing agents, and targeting the degradation pathways in neuronal cells to degrade Tau protein aggregates. Owing to several limitations of the currently-available Tau-directed drugs, further studies are required to generate further effective and safer Tau-based disease-modifying drugs. Here, we review the studies that focused on medicinal plant-derived compounds capable of modulating the Tau protein, which is significantly elevated and hyperphosphorylated in AD and other tauopathies. We mainly considered the studies that focused on Tau protein as a therapeutic target. We reviewed several pertinent papers retrieved from PubMed and ScienceDirect using relevant keywords, with a primary focus on the Tau-targeting compounds from medicinal plants. These compounds include indolines, phenolics, flavonoids, coumarins, alkaloids, and iridoids, which have been scientifically proven to be Tau-targeting candidates for the treatment of AD.

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

Alzheimer's Disease: Progress in the Development of Anti-amyloid Disease-Modifying Therapies

CNS Spectrums ◽  
2007 ◽  
Vol 12 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Daniel D. Christensen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Amyloid Β ◽  
Phase Iii ◽  
Peroxisome Proliferator ◽  
Serious Adverse Events ◽  
Amyloid Disease ◽  
Aβ Aggregation ◽  
Disease Modifying

ABSTRACTThe amyloid hypothesis—the leading mechanistic theory of Alzheimer's disease—states that an imbalance in production or clearance of amyloid β (Aβ) results in accumulation of Aβ and triggers a cascade of events leading to neurodegeneration and dementia. The number of persons with Alzheimer's disease is expected to triple by mid-century. If steps are not taken to delay the onset or slow the progression of Alzheimer's disease, the economic and personal tolls will be immense. Different classes of potentially disease-modifying treatments that interrupt early pathological events (ie, decreasing production or aggregation of Aβ or increasing its clearance) and potentially prevent downstream events are in phase II or III clinical studies. These include immunotherapies; secretase inhibitors; selective Aβ42-lowering agents; statins; anti-Aβ aggregation agents; peroxisome proliferator-activated receptor-gamma agonists; and others. Safety and serious adverse events have been a concern with immunotherapy and γ-secretase inhibitors, though both continue in clinical trials. Anti-amyloid disease-modifying drugs that seem promising and have reached phase III clinical trials include those that selectively target Aβ42 production (eg, tarenflurbil), enhance the activity of α-secretase (eg, statins), and block Aβ aggregation (eg, transiposate).

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 What We Learn from the CTAD 2018 (Clinical Trials Alzheimer’s Disease)

2018 ◽  
pp. 1-2
Author(s):  
B. Vellas ◽  
P. Aisen ◽  
M. Weiner ◽  
J. Touchon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Safety Data ◽  
Phase Iii ◽  
Drug Trials ◽  
New Developments ◽  
Fda Guidance ◽  
Clinical Biomarkers ◽  
Early Alzheimer’S Disease

We are happy to publish the CTAD 2018 abstracts in the present JPAD issue. As you can see many new interesting studies are presented in this issue of the journal: from new drug trials to biomarkers, imaging studies, as well as new clinical outcomes. More specifically, we will have several hot topics presentation on: 1. Major drug trials using bace inhibitors (verubecestat, lanabecestat, atabecestat, elenbecestat…) in the early phase of the disease (APECS early trials…). Both clinical, biomarkers (MRI, CSF, PET) and safety data will be presented. 2. New data on blood biomarkers including a keynote from R. Bateman, and presentations from Araclon and Roche biomarkers. 3. Results from phase III and IIB trials including a novel and multi-targeted oligosaccharide in patients with mild-moderate AD in China; the AMBAR (Alzheimer’s Management By Albumin Replacement) study, the TOMMORROW trial: a trial to delay the onset of MCI due to AD and qualify a genetic biomarker algorithm, the 18-month STEADFAST trial of azeliragon in participants with mild Alzheimer’s Disease; a longitudinal 148-week extension 4. Results 18 from F-AV-1451-A16: a clinicopathological study of the correspondence between flortaucipir PET imaging and post-mortem assessment of tau pathology. 5. Latest developments in anti-amyloid monoclonal antibodies including aducanumab nonnegligible, and new results and data analyses of the BAN2401 study 201 in early AD. 6. New developments with safety and efficacy of lemborexant for sleep-wake regulation in patients with irregular sleep-wake rhythm disorders and Alzheimer’s Disease dementia. 7. Advances with the ABBV-8E12, a humanized anti-tau monoclonal antibody, for the treatment of early Alzheimer’s Disease. 8. Endpoints for early Alzheimer’s Disease clinical trials: interpretation and application of the draft FDA guidance. And many others… It is important to underline that a not negligible number of abstracts concern non amyloid targets (eg: Tau-related targets but also targets outside the classical AD cascade).

scholarly journals Regulatory and Health Technology Assessment Considerations for Disease-Modifying Drugs in Alzheimer’s Disease

CNS Drugs ◽  
2018 ◽  
Vol 32 (12) ◽  
pp. 1085-1090 ◽  
Author(s):  
Jacoline C. Bouvy ◽  
Pall Jonsson ◽  
Diana O’Rourke ◽  
Antonella Santuccione Chadha ◽  
Niklas Hedberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Disease Modifying Drugs ◽  
Disease Modifying
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