Amyloid-directed monoclonal antibodies for the treatment of Alzheimer’s disease: the point of no return?

@article{Panza2014AmyloiddirectedMA,
  title={Amyloid-directed monoclonal antibodies for the treatment of Alzheimer’s disease: the point of no return?},
  author={F. Panza and V. Solfrizzi and B. Imbimbo and G. Logroscino},
  journal={Expert Opinion on Biological Therapy},
  year={2014},
  volume={14},
  pages={1465 - 1476}
}
Introduction: Two humanized monoclonal antibodies, bapineuzumab and solanezumab, directed against the N terminus and mid-region of β-amyloid (Aβ), respectively, were recently tested in large, long-term Phase III trials in patients with mild-to-moderate Alzheimer’s disease (AD). Areas covered: This review discusses current clinical data on solanezumab, bapineuzumab and their failure in Phase III trials to show significant clinical benefits, as well as other monoclonal antibodies under… Expand
Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer’s disease patients
TLDR
Current available drugs against Alzheimer’s disease (AD) target cholinergic and glutamatergic neurotransmissions without affecting the underlying disease process, but put the new drugs at substantial risk of failure. Expand
Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer's Disease
TLDR
Inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid. Expand
Tau-directed approaches for the treatment of Alzheimer’s disease: focus on leuco-methylthioninium
TLDR
Small molecular weight compounds able to inhibit formation of tau oligomers and fibrils have already been tested for Alzheimer’s disease treatment and in the behavioral variant of frontotemporal dementia are underway. Expand
Review of the advances in treatment for Alzheimer disease: Strategies for combating β-amyloid protein.
TLDR
Progress in identifying the molecular basis of AD may provide better models for understanding the causes of this neurodegenerative disease, and the lack of efficacy of solanezumab, demonstrated by 2 recent clinical trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs to be revised. Expand
Review of the advances in treatment for Alzheimer disease: Strategies for combating β-amyloid protein.
TLDR
Progress in identifying the molecular basis of AD may provide better models for understanding the causes of this neurodegenerative disease, and the lack of efficacy of solanezumab, demonstrated by 2 recent Phase III clinical trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs to be revised. Expand
Tau immunotherapies for Alzheimer’s disease
TLDR
The present review article evaluates active and passive immunotherapies in clinical development for AD to date and their potential to significantly improve the treatment of AD going forward. Expand
Tau aggregation inhibitors: the future of Alzheimer’s pharmacotherapy?
TLDR
Covalent mechanisms of tau-aggregation inhibition in AD are predicted to have low utility in vivo, but dimethylfumarate, an electrophile capable of reacting covalently with cysteine sulfhydryls, was approved for oral treatment of multiple sclerosis, suggesting that electrophilic compounds acting through covalent inhibitory mechanisms can be useful therapeutic agents. Expand
Tau-targeting therapies for Alzheimer disease
TLDR
Therapies for Alzheimer disease in clinical trials are gradually shifting from amyloid-β (Aβ)-targeting to tau-targeting approaches, and tau is likely to be a better target than Aβ once cognitive deficits manifest because the tau burden correlates better with clinical impairments than does the Aβ burden. Expand
Immunotherapy for Alzheimer’s Disease
TLDR
Investigation of the mechanisms by which antibodies directed against As aid in clearing the amyloid deposits, how the vaccines might be constructed to overcome self-tolerance without evoking autoimmune reactions, and testing various monoclonal antibody preparations for efficacy in clinical trials are focusing on. Expand
Drug candidates in clinical trials for Alzheimer’s disease
TLDR
The findings from recent clinical trials are systemically reviewed to provide a comprehensive review of novel therapeutic compounds in the treatment and prevention of AD. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 97 REFERENCES
Amyloid-based immunotherapy for Alzheimer's disease in the time of prevention trials: the way forward
TLDR
These primary and secondary prevention trials will definitely test the Aβ cascade hypothesis of AD, and new passive anti-Aβ immunotherapies have been developed and are under clinical testing. Expand
Anti-β-amyloid immunotherapy for Alzheimer's disease: focus on bapineuzumab.
TLDR
The most advanced of these immunological approaches, bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients, appears uncertain, and the results of four ongoing large Phase III trials will tell us if passive anti- Aβ immunization is able to alter the course if this devastating disease. Expand
Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets?
TLDR
Preliminary data from off-label treatment of a small cohort for 3 years with intravenous polyclonal immunoglobulins that appear to target different conformational epitopes indicate a cognitive stabilization, suggesting it might be the more promising strategy reducing the whole spectrum of Aβ-aggregates than to focus on a single aggregate species for immunization. Expand
Solanezumab for the treatment of mild-to-moderate Alzheimer’s disease
TLDR
There is a strong hope that solanezumab may represent the first effective passive vaccine for AD treatment, but skepticism still exists on the ability of the drug to slow the rate of deterioration in patients with fully established disease. Expand
Is there still any hope for amyloid-based immunotherapy for Alzheimer's disease?
TLDR
Both active and passive anti-A&bgr; immunotherapies were shown to clear brain A&b gr; deposits, and two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients with bapineuzumab and solanezumab were disappointing. Expand
Towards Disease-Modifying Treatment of Alzheimers Disease: Drugs Targeting β -Amyloid
TLDR
Several active and passive immunotherapy approaches are under investigation in clinical trials with the aim of accelerating Aβ clearance from the brain of the AD patients, including bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that is being tested in two large late-stage trials. Expand
Towards disease-modifying treatment of Alzheimer's disease: drugs targeting beta-amyloid.
TLDR
Several active and passive immunotherapy approaches are under investigation in clinical trials with the aim of accelerating Abeta clearance from the brain of the AD patients, including bapineuzumab, composed of humanized anti-Abeta monoclonal antibodies, that is being tested in two large late-stage trials. Expand
Immunotherapy for Alzheimer's disease: from anti-β-amyloid to tau-based immunization strategies.
TLDR
Clinical trials on potential disease-modifying drugs, including immunological approaches, should be performed in the early stages of AD based on the new diagnostic criteria of AD and on recent major failures of anti-Aβ drugs in mild-to-moderate AD patients. Expand
Bapineuzumab and solanezumab for Alzheimer's disease: is the ‘amyloid cascade hypothesis' still alive?
TLDR
The marginal benefits of solanezumab are encouraging to support continued evaluation in future studies, and offer small support in favor of the ongoing viability of the ‘amyloid cascade hypothesis' of AD. Expand
Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease.
TLDR
Bapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE ε4 carriers. Expand
...
1
2
3
4
5
...