scholarly journals A IS FOR AMYLOID

2020 ◽  
pp. 1-2
Author(s):  
D.J. Selkoe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Infectious Diseases ◽  
Task Force ◽  
Modern Medicine ◽  
Disease Modifying ◽  
The Brain ◽  
The Eu

In the age of COVID-19, we are reminded that despite the enormous strides modern medicine has made against acute infectious pathogens, we can still be overwhelmed. And in the field of chronic non-infectious diseases of the brain, we, too, have been traveling a long and unpredictable road. For years, there has been a sense of pessimism about the halting march toward disease-modifying treatments for Alzheimer’s disease. But recent events may have begun to part the clouds. In this issue of JPAD, Aisen et al. (1), representing the EU/US CTAD 2019 Task Force, provide a thoughtful perspective on progress in certain anti-amyloid trials and the resultant lessons for our next steps toward success.

scholarly journals BIOMARKER AND CLINICAL TRIAL DESIGN SUPPORT FOR DISEASE-MODIFYING THERAPIES: REPORT OF A SURVEY OF THE EU/US: ALZHEIMER’S DISEASE TASK FORCE

2018 ◽  
pp. 1-7
Author(s):  
J. Cummings ◽  
N. Fox ◽  
B. Vellas ◽  
P. Aisen ◽  
G. Shan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Trial Design ◽  
Task Force ◽  
Clinical Trial Design ◽  
Disease Modification ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
The Eu

BACKGROUND: Disease-modifying therapies are urgently needed for the treatment of Alzheimer’s disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. OBJECTIVES: The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. DESIGN/SETTING/PARTICIANTS: A survey of members of the EU/US Alzheimer’s Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification. MEASUREMENTS/RESULTS/CONCLUSIONS: Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations. CONCLUSION: The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design and biomarkers in support of disease modification. Results of this survey can assist in designing clinical trials of DMTs.

ANTI-TAU TRIALS FOR ALZHEIMER’S DISEASE: A REPORT FROM THE EU/US/CTAD TASK FORCE

2019 ◽  
pp. 1-7
Author(s):  
J. Cummings ◽  
K. Blennow ◽  
K. Johnson ◽  
M. Keeley ◽  
R.J. Bateman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecules ◽  
Task Force ◽  
Phase 1 ◽  
Amyloid Β ◽  
Imaging Studies ◽  
And Function ◽  
The Brain ◽  
The Eu

Efforts to develop effective disease-modifying treatments for Alzheimer’s disease (AD) have mostly targeted the amyloid β (Aβ) protein; however, there has recently been increased interest in other targets including phosphorylated tau and other forms of tau. Aggregated tau appears to spread in a characteristic pattern throughout the brain and is thought to drive neurodegeneration. Both neuropathological and imaging studies indicate that tau first appears in the entorhinal cortex and then spreads to the neocortex. Anti-tau therapies currently in Phase 1 or 2 trials include passive and active immunotherapies designed to prevent aggregation, seeding, and spreading, as well as small molecules that modulate tau metabolism and function. EU/US/CTAD Task Force members support advancing the development of anti-tau therapies, which will require novel imaging agents and biomarkers, a deeper understanding of tau biology and the dynamic interaction of tau and Aβ protein, and development of multiple targets and candidate agents addressing the tauopathy of AD. Incorporating tau biomarkers in AD clinical trials will provide additional knowledge about the potential to treat AD by targeting tau.

Designing drug trials for Alzheimer's disease: What we have learned from the release of the phase III antibody trials: A report from the EU/US/CTAD Task Force

2013 ◽  
Vol 9 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Bruno Vellas ◽  
Maria C. Carrillo ◽  
Cristina Sampaio ◽  
H. Robert Brashear ◽  
Eric Siemers ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Phase Iii ◽  
Drug Trials ◽  
The Eu

scholarly journals Platform Trials to Expedite Drug Development in Alzheimer’s Disease: A Report from the EU/US CTAD Task Force

2021 ◽  
pp. 1-7
Author(s):  
P.S. Aisen ◽  
R.J. Bateman ◽  
M. Carrillo ◽  
R. Doody ◽  
K. Johnson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Lessons Learned ◽  
Combination Therapies ◽  
Diverse Range ◽  
Interim Analyses ◽  
Treatment Regimens ◽  
Experimental Therapies ◽  
The Eu

A diverse range of platforms has been established to increase the efficiency and speed of clinical trials for Alzheimer’s disease (AD). These platforms enable parallel assessment of multiple therapeutics, treatment regimens, or participant groups; use uniform protocols and outcome measures; and may allow treatment arms to be added or dropped based on interim analyses of outcomes. The EU/US CTAD Task Force discussed the lessons learned from the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) platform trial and the challenges addressed by other platform trials that have launched or are in the planning stages. The landscape of clinical trial platforms in the AD space includes those testing experimental therapies such as DIAN-TU, platforms designed to test multidomain interventions, and those designed to streamline trial recruitment by building trial-ready cohorts. The heterogeneity of the AD patient population, AD drugs, treatment regimens, and analytical methods complicates the design and execution of platform trials, yet Task Force members concluded that platform trials are essential to advance the search for effective AD treatments, including combination therapies.

COMMENTARY: COMBINATION THERAPY FOR ALZHEIMER’S DISEASE: PERSPECTIVES OF THE EU/US CTAD TASK FORCE

2019 ◽  
pp. 1-2
Author(s):  
E. Siemers
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
European Union ◽  
Clinical Trials ◽  
Task Force ◽  
Pharmaceutical Companies ◽  
The European Union ◽  
Combination Therapies ◽  
Regulatory Pathways ◽  
The Eu

In October 2018, the European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) met to discuss an increasingly important topic, the scientific, regulatory, and logistical challenges to the development of combination therapies for AD. Challenges related to ever-changing scientific knowledge, challenges related to complex regulatory pathways and challenges related to the necessity for pharmaceutical companies to collaborate must all be addressed. These challenges must be met since task Force members unanimously agreed that successful treatment of AD will likely require combination therapies targeting multiple mechanisms and pathways.

scholarly journals Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer’s disease

2020 ◽  
Vol 52 (8) ◽  
pp. 1275-1287
Author(s):  
Seong Su Kang ◽  
Eun Hee Ahn ◽  
Keqiang Ye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Strategy ◽  
Senile Plaques ◽  
Tau Pathology ◽  
Disease Modifying ◽  
Tau Aggregation ◽  
The Brain ◽  
Insight Into

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease with age as a major risk factor. AD is the most common dementia with abnormal structures, including extracellular senile plaques and intraneuronal neurofibrillary tangles, as key neuropathologic hallmarks. The early feature of AD pathology is degeneration of the locus coeruleus (LC), which is the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The spread of Tau deposits is first initiated in the LC and is transported in a stepwise manner from the entorhinal cortex to the hippocampus and then to associative regions of the neocortex as the disease progresses. Most recently, we reported that the NE metabolite DOPEGAL activates delta-secretase (AEP, asparagine endopeptidase) and triggers pathological Tau aggregation in the LC, providing molecular insight into why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in the disease and how δ-secretase mediates the spread of Tau pathology to the rest of the brain. This review summarizes our current understanding of the crucial role of δ-secretase in driving and spreading AD pathologies by cleaving multiple critical players, including APP and Tau, supporting that blockade of δ-secretase may provide an innovative disease-modifying therapeutic strategy for treating AD.

Disease-modifying trials in Alzheimer's disease: a European task force consensus

2007 ◽  
Vol 6 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Bruno Vellas ◽  
Sandrine Andrieu ◽  
Cristina Sampaio ◽  
Gordon Wilcock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Disease Modifying ◽  
European Task

scholarly journals Tau Based Therapeutics: Alternative Approaches in the War on Alzheimer’s Disease

2019 ◽  
pp. 1-2
Author(s):  
M. Grundman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Task Force ◽  
Meeting Report ◽  
Distant Future ◽  
Alternative Approaches ◽  
The Eu

This issue of The Journal of Prevention of Alzheimer’s Disease highlights EU/US/CTAD TASK FORCE discussions on the topic of tau-based therapeutics that were held in association with the 2018 CTAD meeting. The EU/US/CTAD TASK FORCE meeting report (1) is particularly timely given that a number of tau-based therapies are currently being evaluated in clinical trials and will report their results in the not-too-distant future.

scholarly journals Don’t Forget the Brain: Lifestyle Medicine in the Century of Neurodegeneration

2016 ◽  
Vol 11 (4) ◽  
pp. 361-363
Author(s):  
Bruce Thompson ◽  
Darren Morton ◽  
Lillian Kent
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lifestyle Factors ◽  
Lifestyle Medicine ◽  
Disease Modifying Therapy ◽  
The Future ◽  
Disease Modifying ◽  
The Brain

Neurology is often not discussed in lifestyle medicine circles, but it might be an area that will propel the cause of lifestyle medicine in the future. This is especially relevant in increasingly common neurodegenerative conditions such as Alzheimer’s disease, which have no known disease modifying therapy but lifestyle factors are implicated in causation.

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