alzheimer’s disease platforms for translational research
TRANSCRIPT
![Page 1: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/1.jpg)
Alzheimer’s disease
Platforms for translational research
![Page 2: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/2.jpg)
The Problem
• More than 36m people with dementia
• Consumes 1% global GDP
• Serial trials failure
![Page 3: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/3.jpg)
January 2014
Imprecision medicine !
![Page 4: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/4.jpg)
• Diversify target development
• Trials in prodromal or preclinical disease
• Rapid trials with early read-outs
The Solution
![Page 5: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/5.jpg)
Alzheimer’s Research UK Oxford
DrugDevelopment
Institute
Wellcome Neuroinflammation
consortium
Wellcome Target Enabling Packages
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
Pre-competitive data driven
drug development
Pre-competitive cohort repurposing for experimental medicine
Pre-competitive reutilisation of research
and real-world data
Pre-competitive data driven
PoC/PhII
Dementias Platform UK
Dementia Discovery cohorts (n=2m)
Dementia UK BioBank cohort (n=10k)
Deep and Frequent Phenotyping cohort
Collaboration for translational research in dementia
NIHR Translational Research Collaboration
in dementia (TRC-D)
![Page 6: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/6.jpg)
placebo
Rx
cognition outcomes
Trial cohort
![Page 7: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/7.jpg)
Cohort A
Cohort B
Cohort C
integration
placebo
Rx … n
Adaptation by change in interm
ediate phenotype
Rx 1
Rx 2
Adaptation on cognition outcom
es
Selection criteria
Trial cohort
Readiness cohort
EPAD Registry
![Page 8: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/8.jpg)
Alzheimer’s Research UK Oxford
DrugDevelopment
Institute
Wellcome Neuroinflammation
consortium
Wellcome Target Enabling Packages
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
Pre-competitive data driven
drug development
Pre-competitive cohort repurposing for experimental medicine
Pre-competitive reutilisation of research
and real-world data
Pre-competitive data driven
PoC/PhII
Dementias Platform UK
Dementia Discovery cohorts (n=2m)
Dementia UK BioBank cohort (n=10k)
Deep and Frequent Phenotyping cohort
Collaboration for translational research in dementia
NIHR Translational Research Collaboration
in dementia (TRC-D)
![Page 9: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/9.jpg)
http://www.dementiasplatform.uk/
Dementias Platform UK
![Page 10: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/10.jpg)
Adapted from Sperling et al (2011) Alzheimer’s and dementia 7 280-92
Biomarkers for secondary prevention
Stratification markers
Progression markers
![Page 11: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/11.jpg)
UK Biobank for Dementia Research
• 500,000 participants; baseline assessments 2005-8
• Web-based questionnaires for additional exposures and outcomes (cognition, mental health, occupation..)
• Multimodal imaging in 100,000 - brain, cardiac and body fat MRI; bone & joint DEXA; 3D carotid ultrasound
• Repeat Neuroimaging, cognition and sampling in 20,000
• Genotyping of all participants (820,000 SNPs)
• Connectivity to EMRs for mental health
![Page 12: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/12.jpg)
A biomarker funnel
55+
![Page 13: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/13.jpg)
Alzheimer’s Research UK Oxford
DrugDevelopment
Institute
Wellcome Neuroinflammation
consortium
Wellcome Target Enabling Packages
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
Pre-competitive data driven
drug development
Pre-competitive cohort repurposing for experimental medicine
Pre-competitive reutilisation of research
and real-world data
Pre-competitive data driven
PoC/PhII
Dementias Platform UK
Dementia Discovery cohorts (n=2m)
Dementia UK BioBank cohort (n=10k)
Deep and Frequent Phenotyping cohort
Collaboration for translational research in dementia
NIHR Translational Research Collaboration
in dementia (TRC-D)
![Page 14: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/14.jpg)
European Medical Information Framework
![Page 15: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/15.jpg)
Data available through consortium Large variety in “types” of data
Data is available from more than 53 million subjects from seven EU countries, including
Primary care data sets
Hospital data Administrative data
Regional record-linkage
systems
Registries and cohorts (broad
and disease specific)
Biobanks
>40,000subjects in AD cohorts
>90,000subjects in metabolic cohorts
![Page 16: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/16.jpg)
EMIF Catalogue
![Page 17: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/17.jpg)
Research cohorts on AD or aging
• Type of cohorts:– Population-based cohorts– Clinical cohorts– National multicenter studies – European multicenter studies– Clinical trial cohorts
![Page 18: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/18.jpg)
Data available through cohorts in catalogue
Number of subjects
Controls SCI MCI
All 31219 3173 11976
Plasma 3537 1764 3961
DNA 8763 3163 5731
RNA 1637 484 2128
CSF 846 1336 3757
Urine 2307 1116 2349
MRI 3449 1035 5586
FDG-PET 551 308 1942
Amyloid PET 335 143 492
EEG 301 773 1173Either access to results from analysis or access to samples/scans
![Page 19: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/19.jpg)
Alzheimer’s Research UK Oxford
DrugDevelopment
Institute
Wellcome Neuroinflammation
consortium
Wellcome Target Enabling Packages
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
IMI-EPAD
European Prevention of Alzheimer’s
disease
Readiness register, cohort
and Early Phase
Trials
Pre-competitive data driven
drug development
Pre-competitive cohort repurposing for experimental medicine
Pre-competitive reutilisation of research
and real-world data
Pre-competitive data driven
PoC/PhII
Dementias Platform UK
Dementia Discovery cohorts (n=2m)
Dementia UK BioBank cohort (n=10k)
Deep and Frequent Phenotyping cohort
Collaboration for translational research in dementia
NIHR Translational Research Collaboration
in dementia (TRC-D)
![Page 20: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/20.jpg)
Target Enabling and Development
• Oxford basic sciences and neurodegeneration research
• Building on SGC success - TEPs• O3DI collaborative group and beyond
• Target selection by Data and by Biomarkers• Open Innovation• Bringing to dementia research tools and pathways
from– Inflammation– Oncology– Metabolic disease
![Page 21: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/21.jpg)
The Drug Discovery Alliance
• Host Institution is a centre of
excellence in neurodegenerative
disease
• The Institute is integrated into the
host environment
• The DDI scientists are experts in
translating basic science into
therapies
• Provide clear mission
• Stable funding
• £30M over 5 years
• ~30 staff per institute
![Page 22: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/22.jpg)
Partners in the Oxford DDI
Lead Academic Scientist
Prof. Simon Lovestone
Prof. Chas Bountra
Co-applicant PIs
DPAG
NDCN
Dept Psychiatry
LICR
Kennedy Inst. Rheumatology
SGC
TDI / UK NPSC
StemBANCC
CSO John Davis
HoC to be appointed
HoB to be appointed
Chemistry team
Biology teamCollaborating
companies
CROs
Pharma
Research Expertise Drug Discovery Expertise
Portfolio
Project Teams
Robust Lead Series
with proof of principle
New drug discovery programmes
Collaborators
Eg.
Cardiff
KCL
Southampton
Dundee
Other DDIs
Under-exploited
Novel
Targets
![Page 23: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/23.jpg)
Global problems require global solutions
![Page 24: Alzheimer’s disease Platforms for translational research](https://reader035.vdocument.in/reader035/viewer/2022062519/56649e9d5503460f94b9d8ae/html5/thumbnails/24.jpg)
With thanks to….> 50 executive members> 150 principal investigators> 500 scientists>1500 collaborators> 50,000 volunteers> 50,000,000 individuals contributing data> 200,000,000 euros from funders