scholarly journals NEXT-GENERATION ALZHEIMER’S THERAPEUTICS: LEVERAGING DEEP BIOLOGY

2020 ◽  
pp. 1-2
Author(s):  
F.M. Longo ◽  
S.M. Massa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Diversity ◽  
Task Force ◽  
Next Generation ◽  
Disease Modification ◽  
Task Force Report ◽  
Field Point

A recent EU/US CTAD Task Force Report focused on non-amyloid approaches to Alzheimer’s disease (AD) modification (1). While the broad range of targets and therapies highlighted is in some ways sobering, several themes and advances in the field point to principles and technologies that are encouraging and will likely accelerate progress. These themes include: the view that amyloid and non-amyloid approaches might ultimately be complementary or synergistic; the biological diversity of approaches; emerging -omics strategies that might help guide such options; and finally, the incorporation of aging biology into perspectives of target prioritization and disease modification.

scholarly journals NON-AMYLOID APPROACHES TO DISEASE MODIFICATION FOR ALZHEIMER’S DISEASE: AN EU/US CTAD TASK FORCE REPORT

2020 ◽  
pp. 1-6
Author(s):  
S. Gauthier ◽  
P.S. Aisen ◽  
J. Cummings ◽  
M.J. Detke ◽  
F.M. Longo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Neurotrophin Receptor ◽  
General Strategy ◽  
Disease Modification ◽  
Task Force Report ◽  
Receptor Modulation ◽  
Alternative Approaches ◽  
Therapy Strategies

While amyloid-targeting therapies continue to predominate in the Alzheimer’s disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of alternative treatment approaches, which would include increased partnerships and collaborations, improved trial designs, and further exploration of combination therapy strategies.

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.

scholarly journals PLASMA BIOMARKERS OF AD EMERGING AS ESSENTIAL TOOLS FOR DRUG DEVELOPMENT: AN EU/US CTAD TASK FORCE REPORT

2019 ◽  
pp. 1-5
Author(s):  
R.J. Bateman ◽  
K. Blennow ◽  
R. Doody ◽  
S. Hendrix ◽  
S. Lovestone ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Task Force ◽  
Accurate Estimate ◽  
Current Status ◽  
The European Union ◽  
Neurofilament Light ◽  
Stakeholder Collaboration ◽  
Task Force Report

There is an urgent need to develop reliable and sensitive blood-based biomarkers of Alzheimer’s disease (AD) that can be used for screening and to increase the efficiency of clinical trials. The European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) discussed the current status of blood-based AD biomarker development at its 2018 annual meeting in Barcelona, Spain. Recent improvements in technologies to assess plasma levels of amyloid beta indicate that a single sample of blood could provide an accurate estimate of brain amyloid positivity. Plasma neurofilament light protein appears to provide a good marker of neurodegeneration, although not specific for AD. Plasma tau shows some promising results but weak or no correlation with CSF tau levels, which may reflect rapid clearance of tau in the bloodstream. Blood samples analyzed using -omics and other approaches are also in development and may provide important insight into disease mechanisms as well as biomarker profiles for disease prediction. To advance these technologies, international multidisciplinary, multi-stakeholder collaboration is essential.

Alzheimer’s disease therapeutic trials: EU/US task force report on recruitment, retention, and methodology

2012 ◽  
Vol 16 (4) ◽  
pp. 339-345 ◽  
Author(s):  
B. Vellas ◽  
◽  
H. Hampel ◽  
M. E. Rouge-Bugat ◽  
M. Grundman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Task Force Report ◽  
Therapeutic Trials

scholarly journals EDITORIAL: BLOOD TESTS FOR ALZHEIMER’S DISEASE AND RELATED DISORDERS

2019 ◽  
pp. 1-2
Author(s):  
E.M. Reiman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Neurofibrillary Tangle ◽  
Neuritic Plaque ◽  
Plaque Burden ◽  
Neurofilament Light ◽  
Task Force Report ◽  
Blood Tests ◽  
Wide Range

This issue of the Journal of Prevention of Alzheimer’s Disease (AD) includes a timely Clinical Trials on AD Task Force Report on promising blood tests for AD and related disorders (1). It highlights the promise of recently developed plasma amyloid-β42/40 (Aβ42/40) measurements for the assessment of neuritic plaque burden (e.g., reference 2), ultrasensitive neurofilament light (NfL) measurements for the assessment of ongoing neuroaxonal injury in a wide range of neurological disorders (3), and their potential roles in evaluation of interventions to treat and prevent the clinical onset of AD. It also considers recently developed plasma total-tau measurements, an indicator of neuronal injury and/or Aβ-mediated tau secretion (4), plasma phospho-tau measurements, a potential indicator of neurofibrillary tangle burden, and the ongoing effort to develop high-dimensional plasma genomic, transcriptomic, metabolomic, lipidomic, and proteomic profiles.

Prevention trials in Alzheimer's disease: An EU-US task force report

2011 ◽  
Vol 95 (4) ◽  
pp. 594-600 ◽  
Author(s):  
Bruno Vellas ◽  
Paul S. Aisen ◽  
Cristina Sampaio ◽  
Maria Carrillo ◽  
Philip Scheltens ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Task Force Report ◽  
Prevention Trials

Measuring Disease Modification in Alzheimer's Disease

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S1) ◽  
pp. 11-14
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immunoglobulin A ◽  
Disease Process ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Modification ◽  
Amyloid Disease ◽  
Therapeutic Modalities ◽  
Disease Modifying

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

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