Imaging-Based Measures of Disease Progression in Clinical Trials of Disease-Modifying Drugs for Alzheimer Disease

2003 ◽  
Vol 11 (2) ◽  
pp. 146-159 ◽  
Author(s):  
Brandy Matthews ◽  
Eric R. Siemers ◽  
P. David Mozley
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
Disease Progression ◽  
Disease Modifying Drugs ◽  
Disease Modifying

Clinical symptoms, underlying pathogenesis, and the prospect of tailored therapies have all benefited from genetic discoveries in Parkinson's disease

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Clinical Trials ◽  
Clinical Symptoms ◽  
The Other ◽  
Patient Classification ◽  
Medium Term ◽  
Disease Modifying Drugs ◽  
Disease Biology ◽  
Targeted Treatments ◽  
Disease Modifying ◽  
Underlying Pathogenesis

Clinical symptoms, underlying pathogenesis, and the prospect of tailored therapies have all benefited from genetic discoveries in Parkinson's disease.Even as our understanding of disease biology improves, there are still knowledge gaps that must be filled in the future. Reliable biomarkers that uniquely recapitulate pathophysiological aspects are necessary for patient classification and medication response tracking. Genetic testing is essential in 'idiopathic' or 'sporadic' PD patients to identify those who would benefit from genotype-driven treatment. Genotype-dependent segmentation of research participants will broaden the possible usefulness of targeted treatments. Biomarker-assisted clinical trials will benefit tremendously from new adaptable designs. Recent breakthroughs in genotype-driven therapy, on the other hand, should deliver considerable benefits for Parkinson's patients in the medium term and lead to the development of the first disease-modifying drugs.

Disease progression among multiple sclerosis patients before and during a disease-modifying drug program: a longitudinal population-based evaluation

2009 ◽  
Vol 15 (11) ◽  
pp. 1286-1294 ◽  
Author(s):  
PJ Veugelers ◽  
JD Fisk ◽  
MG Brown ◽  
K. Stadnyk ◽  
IS Sketris ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Program Effectiveness ◽  
Population Based ◽  
Eligibility Criteria ◽  
Disease Modifying Drugs ◽  
Regression Methods ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Randomized controlled trials have demonstrated the efficacy of disease-modifying drugs (DMDs) in persons with relapsing—remitting multiple sclerosis (MS) and secondary progressive MS with superimposed relapses. However, these brief studies of selected patients have focused mainly on reducing attacks and must be complemented by evaluations in ‘realworld’ clinical settings to establish the effectiveness of DMD programs in slowing disease progression and to inform health policy and program decision-making. We assessed the effectiveness of DMDs as administered in a comprehensive publicly funded drug insurance program that provides DMDs to a geographically defined population of MS patients who meet specific eligibility criteria. Data from 1752 MS patients (10,312 assessments) seen between 1980 and 2004 at a regional MS Clinic serving the entire population of Nova Scotia, Canada were analysed. Using survival methods we observed a statistically significant reduction in disease progression to specific Expanded Disability Status Scale endpoints following the introduction of this program. Subgroup analyses of patients eligible for treatment using hierarchical linear regression methods also suggested that disease progression was slowed in patients treated with the first DMD prescribed. These findings provide evidence supporting DMD program effectiveness that can be used to inform the broader implementation of such programs.

scholarly journals Reasons for Failed trials of Disease-modifying Treatments for Alzheimer Disease and their Contribution in Recent Research

2019 ◽  
Author(s):  
Konstantina G. Yiannopoulou ◽  
Aikaterini I. Anastasiou ◽  
Venetia Zachariou ◽  
SH Pelidou
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Alzheimer Disease ◽  
Drug Development ◽  
Inappropriate Drug ◽  
Trial Methodology ◽  
Prodromal Ad ◽  
Csf Biomarker ◽  
Disease Modifying ◽  
Drug Development Research

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

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 DIAN-TU ARGENTINA

2021 ◽  
Vol 2 (1) ◽  
pp. e00173805
Author(s):  
Patricio Chrem-Mendez ◽  
Pablo Bagnati
Keyword(s):  
Clinical Trials ◽  
Risk Factor ◽  
Alzheimer Disease ◽  
Neurodegenerative Disease ◽  
New Disease ◽  
Main Risk Factor ◽  
Classical Form ◽  
Novel Therapeutics ◽  
Disease Modifying ◽  
Global Aging

Alzheimer’s disease is, by far the first, cause of dementia and the more frequent neurodegenerative disease. Considered as a result of multifactorial causes, aging is the main risk factor for the classical form of the disease and because of global aging, a very significant increase in the prevalence is expected in the upcoming decades, especially in countries in development. Several drugs with different targets have been tried so far and, still with no success. Frenzied efforts seeking a new disease-modifying drug are constantly being pursued and innovative models of the clinical trials have emerged. The DIAN initiative studies individuals with known mutations in the deterministic genes of the disease. Autosomal Dominantly Alzheimer Disease (ADAD) showed to be a more predictable model in terms of whom and when will get the disease. This allows testing novel therapeutics agents by choosing the drug according to the biological moment of the disease. But ADAD is also a uniquely human story full of courage and hope. The DIAN trial has started in Argentina and a new anti-tau age has begun as well.

scholarly journals Thinking Outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke

2021 ◽  
Vol 10 (4) ◽  
pp. 630
Author(s):  
Athina-Maria Aloizou ◽  
Vasileios Siokas ◽  
Georgia Pateraki ◽  
Ioannis Liampas ◽  
Christos Bakirtzis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Early Intervention ◽  
Cause Of Death ◽  
Nervous Tissue ◽  
Inflammatory Process ◽  
Disease Modifying Drugs ◽  
Disease Modifying ◽  
Positive Results

Ischemic stroke (IS) is a major cause of death and disability, despite early intervention. Thrombo-inflammation, the inflammatory process triggered by ischemia, is a concept that ties IS with multiple sclerosis (MS), under the wider ‘umbrella’ of neuroinflammation, i.e., the inflammation of the nervous tissue. Drawing from this, numerous studies have explored the potential of MS disease-modifying drugs in the setting of IS. In this review, we present the available studies and discuss their potential in ameliorating IS outcomes. Based on our search, the vast majority of the studies have been conducted on animals, yielding mostly positive results. Two clinical trials involving natalizumab showed that it does not confer any benefits, but four human studies regarding fingolimod have showcased its potential in improving recovery prospects. However, concerns on safety and other issues are raised, and basic questions still need to be answered.

scholarly journals Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 97 ◽  
Author(s):  
Konstantina G. Yiannopoulou ◽  
Aikaterini I. Anastasiou ◽  
Venetia Zachariou ◽  
Sygkliti-Henrietta Pelidou
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Alzheimer Disease ◽  
Drug Development ◽  
Inappropriate Drug ◽  
Trial Methodology ◽  
Prodromal Ad ◽  
Csf Biomarker ◽  
Disease Modifying ◽  
Drug Development Research

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and Cerebrospinal fluid (CSF) biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are assessed in clinical trials. The above-mentioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are relevant to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

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