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 Translating the biology of aging into novel therapeutics for Alzheimer disease

Neurology ◽  
2018 ◽  
Vol 92 (2) ◽  
pp. 84-93 ◽  
Author(s):  
Yuko Hara ◽  
Nicholas McKeehan ◽  
Howard M. Fillit
Keyword(s):  
Risk Factor ◽  
Alzheimer Disease ◽  
Neurodegenerative Disease ◽  
Old Age ◽  
Chronic Illnesses ◽  
Aging Brain ◽  
Novel Therapeutics ◽  
The Many ◽  
Biology Of Aging ◽  
New Generation

Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer disease (AD), a progressive neurodegenerative disease with currently no therapies that prevent, slow, or halt disease progression. Like other chronic diseases of old age, the progressive pathology of AD begins decades before the onset of symptoms. Many decades of research in biological gerontology have revealed common processes that are relevant to understanding why the aging brain is vulnerable to AD. In this review, we frame the development of novel therapeutics for AD in the context of biological gerontology. The many therapies currently in development based on biological gerontology principles provide promise for the development of a new generation of therapeutics to prevent and treat AD.

scholarly journals Risks and benefits of unapproved disease-modifying treatments for neurodegenerative disease

Neurology ◽  
2019 ◽  
Vol 94 (1) ◽  
pp. e1-e14 ◽  
Author(s):  
Aden C. Feustel ◽  
Amanda MacPherson ◽  
Dean A. Fergusson ◽  
Karl Kieburtz ◽  
Jonathan Kimmelman
Keyword(s):  
Alzheimer Disease ◽  
Adverse Events ◽  
Parkinson Disease ◽  
Neurodegenerative Disease ◽  
Active Treatment ◽  
Huntington Disease ◽  
Mean Difference ◽  
Serious Adverse Events ◽  
Disease Modifying ◽  
Standardized Mean Difference

ObjectiveTo determine whether patients randomized to unapproved, disease-modifying interventions in neurodegenerative disease trials have better outcomes than patients randomized to placebo by performing a systematic review and meta-analysis of risk and benefit experienced by patients in randomized placebo-controlled trials testing investigational treatments for Alzheimer disease, Parkinson disease, Huntington disease, or amyotrophic lateral sclerosis (ALS).MethodsWe searched MEDLINE, Embase, and ClinicalTrials.gov for results of randomized trials testing non–Food and Drug Administration–approved, putatively disease-modifying interventions from January 2005 to May 2018. Trial characteristics were double-extracted. Coprimary endpoints were the treatment advantage over placebo on efficacy (standardized mean difference in outcomes) and safety (risk ratios of serious adverse events and withdrawals due to adverse events), calculated with random effects meta-analyses. The study was registered on PROSPERO (CRD42018103798).ResultsWe included 113 trials (n = 39,875 patients). There was no significant efficacy advantage associated with assignment to putatively disease-modifying interventions compared to placebo for Alzheimer disease (standardized mean difference [SMD] −0.03, 95% confidence interval [CI] −0.07 to 0.01), Parkinson disease (SMD −0.09, 95% CI −0.32 to 0.15), ALS (SMD 0.02, 95% CI −0.25 to 0.30), or Huntington disease (0.02, 95% CI −0.27 to 0.31). Patients with Alzheimer disease assigned to active treatment were at higher risk of experiencing serious adverse events (risk ratio [RR] 1.15, 95% CI 1.04–1.27) and withdrawals due to adverse events (RR 1.44, 95% CI 1.21–1.70).ConclusionsAssignment to active treatment was not beneficial for any of the indications examined and may have been slightly disadvantageous for patients with Alzheimer disease. Our findings suggest that patients with neurodegenerative diseases are not, on the whole, harmed by assignment to placebo when participating in trials.

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 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.

scholarly journals Neurodegenerative Disease Phenotypes in Carriers of MAPT p.A152T, A Risk Factor for Frontotemporal Dementia Spectrum Disorders and Alzheimer Disease

2013 ◽  
Vol 27 (4) ◽  
pp. 302-309 ◽  
Author(s):  
Suzee E. Lee ◽  
Maria C. Tartaglia ◽  
Görsev Yener ◽  
Sermin Genç ◽  
William W. Seeley ◽  
...  
Keyword(s):  
Risk Factor ◽  
Alzheimer Disease ◽  
Neurodegenerative Disease ◽  
Frontotemporal Dementia ◽  
Disease Phenotypes ◽  
Spectrum Disorders

Do clinical trials for new disease modifying treatments include real world patients with multiple sclerosis?

2020 ◽  
Vol 39 ◽  
pp. 101931
Author(s):  
Juan Ignacio Rojas ◽  
Agustín Pappolla ◽  
Liliana Patrucco ◽  
Edgardo Cristiano ◽  
Francisco Sánchez
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Real World ◽  
New Disease ◽  
Disease Modifying

Phosphodiesterase 10 Inhibitors: New Disease Modifying Drugs for Parkinson’s Disease?

2014 ◽  
Vol 21 (10) ◽  
pp. 1171-1187 ◽  
Author(s):  
A.M. Garcia ◽  
M. Redondo ◽  
A. Martinez ◽  
C. Gil
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
New Disease ◽  
Disease Modifying Drugs ◽  
Disease Modifying

Eyelid Dermatitis and Contact Sensitization to Nickel: Results from an Italian Multi-Centric Observational Study

2019 ◽  
Vol 19 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Alessandro Borghi ◽  
Monica Corazza ◽  
Elisa Maietti ◽  
Cataldo Patruno ◽  
Maddalena Napolitano ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Contact Sensitization ◽  
Main Risk Factor ◽  
Nickel Allergy ◽  
Cross Sectional ◽  
Triggering Factor ◽  
Irritant Action ◽  
Allergic Contact

Background: Due to the sensitizing constituents of eye cosmetics, allergic contact dermatitis is considered a frequent cause of eyelid dermatitis. An association between eyelid dermatitis and nickel contained in make-ups remains controversial. Objective: The study aimed to assess the association between nickel allergy, the use of pigmented makeup products and self-reported eyelid dermatitis. Method: This multi-centric, cross-sectional study enrolled 165 women sensitized to nickel (patients) and 103 women without intolerance to metals (controls). We recorded: demographics, atopy, use of pigmented eye cosmetics (mascara, eyeshadow, eyeliner, eyebrow pencil), and previous eyelid dermatitis. Among the patients, any co-sensitization to cosmetics or metals was recorded. Results: 87.3% of the patients and 91.3% of the controls reported their use of eye make-up; 44.9% and 52.4%, respectively, reported previous episodes of eyelid dermatitis, without significant differences. The occurrence of eyelid dermatitis was significantly associated with the use of eye make-up products, both in general and considering each product separately. Age, atopy, or co-sensitization to other metals or cosmetics did not affect the occurrence of eyelid dermatitis. Conclusion: Nickel allergy should not be considered the main risk factor for eyelid dermatitis. The use of pigmented eye make-up may be a triggering factor for eyelid dermatitis, probably due to an irritant action.

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