Striving for an Integrated drug-development Process for Neurodegeneration: the Coalition Against Major Diseases

Romero, Klaus; Corrigan, Brian; Neville, Jon; Kopko, Steve; Cantillon, Marc

doi:10.2217/nmt.11.51

Cited by 13 publications

(9 citation statements)

References 17 publications

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“…ADNI data have been combined with additional placebo data from clinical trials conducted in AD and are publicly available on the Coalition Against Major Disease Web site (http://www.c-path.org/CAMDcodr.cfm) for additional data mining [227]. Modeling efforts have highlighted the importance of age, baseline cognitive status, and APOE status on disease progression rates; a model is currently under qualification review through newly developed European Medicines Agency (EMA) and FDA qualification procedures.…”

Section: Development and Assessment Of Treatments For Ad: Perspectimentioning

confidence: 99%

The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

Weiner

Veitch

Aisen

et al. 2013

Alzheimer's & Dementia

656

428

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The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates for the detection of AD in its preclinical stages; (5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities, whereas MRI measures of change were shown to be the most efficient outcome measures; (6) the confirmation of the AD risk loci CLU, CR1, and PICALM and the identification of novel candidate risk loci; (7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia, and Australia; (8) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (9) the establishment of infrastructure to allow sharing of all raw and ...

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Section: Development and Assessment Of Treatments For Ad: Perspectimentioning

confidence: 99%

The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

Weiner

Veitch

Aisen

et al. 2013

Alzheimer's & Dementia

656

428

View full text Add to dashboard Cite

show abstract

“…Results from ADNI data have been combined with additional placebo data from clinical trials conducted in AD and are publicly available on the Coalition Against Major Diseases (CAMD) Web site for additional data mining [227]. Modeling efforts have highlighted the importance of age, baseline cognitive status, and APOE status on disease progression rates; a model is currently under qualification review through newly developed European Medicines Agency (EMA) and FDA qualification procedures.…”

Section: Development and Assessment Of Treatments For Ad: Perspectmentioning

confidence: 99%

2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

Weiner

Veitch

Aisen

et al. 2015

Alzheimer's & Dementia

273

224

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The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer’s Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; (6) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Multimodal methods incorporating APOE status and longitudinal MRI proved most highly predictive of future decline. Refinements of clinical tests used as outcome measures such as clinical dementia rating-sum of boxes further reduced sample sizes; (7) the pioneering of genome-wide association studies that leverage quantitative imaging and biomarker phenotypes, including longitudinal data, to confirm recently identified loci, CR1, CLU, and PICALM and to identify novel AD risk loci; (8) worldwide impact through the establishment of ADNI-like programs in Japan, Australia, Argentina, Taiwan, China, Korea, Europe, and Italy; (9) understanding ...

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“…How CAMD accelerates drug development CAMD has successfully facilitated collaborative efforts to develop tools aimed at expediting drug development and maximizing the potential for success in future drug trials [6][7][8]. Already, these efforts have led to the submission and acceptance of a qualification opinion by the EMA on the use of hippocampal volume as a biomarker for enriching predementia clinical trials with appropriate subjects [9], the establishment of a database incorporating placebo data from 6500 subjects, the development of the first AD CDISC clinical trial data standard that will facilitate data sharing and the first ever regulatory endorsement of a clinical trial simulation tool for AD.…”

Section: What's Holding Up Progress?mentioning

confidence: 99%

Alzheimer’s disease from researcher to caregiver: a personal journey and call to action

Stephenson

2014

Expert Review of Neurotherapeutics

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Striving for an Integrated drug-development Process for Neurodegeneration: the Coalition Against Major Diseases

Cited by 13 publications

References 17 publications

The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

Alzheimer’s disease from researcher to caregiver: a personal journey and call to action

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