Joint Programming in

Neurodegenerative Disease Research (JPND)

Coordinating approaches to research across Europe

Adriana Maggi, JPND Vice-chair

IMI2 SGG Meeting

Brussels 22/1/2015

JPND brings together

• Researchers (Basic, Clinical, Healthcare/Social)

• National Funding Bodies

• National Research Strategies and Investments

We cannot tackle neurodegenerative

diseases by acting as single countries

Albania

Austria

Belgium

CanadaCroatia

Czech Republic

Denmark

Finland

France

Germany

Greece

Hungary

Ireland

Israel

Italy

Luxembourg

NetherlandsNorway

Poland

Portugal

Romania

Slovakia

Slovenia

Spain

Sweden

Switzerland

Turkey

United Kingdom

JPND is the largest global ND research initiative

led by EU countries, with 28 participating

EU member states

Associated countries

Third countries

Increasing coordination of national

research programmes to improve

impact and effectiveness

Management Board• 28 countries represented

• Members mandated to act

Executive Board• Philippe Amouyel, Chair - France

• Adriana Maggi, Vice-Chair - Italy

• Robin Buckle - UK

• Mogens Horder - Denmark

• Marlies Dorlochter - Germany

Scientific Advisory Board• 18 Members, chosen for scientific excellence

• Industry and Patient Organisations represented

Organisation

Steering CommitteeExecutive Board +

• Rainer Girgenrath - Germany

• Edvard Beem - Netherlands

Martin Rossor

•Thomas Gasser

JPND Scientific Board

Jesús

de Pedro Cuesta

Philip Scheltens

•Bengt Winblad

Thomas Rooney Myrra

Vernooij-Dassen

•Stefano F. Cappa

•Leszek

•Kaczmarek

•John Hardy

•Bruno Dubois

•Brian Fiske

•Eric Karran

•Charles Scerri

Martin Knapp

Scope of JPND Research

Scientific Medical

Social

Defragmentation

– what JPND is all about…

STRATEGIC RESEARCH AGENDA

ALIGNMENT OF EU COUNTRIES

ON COMMON RESEARCH GOALS

SRA Implementation

JPND Action Groups

Action Group Recommendations

“Rapid Action” Call for working groups

Coordination and development of best practice

Ten JPND working groups to address methodological challenges

for longitudinal cohort studies such as:

• Cognition / Functional assessment

• Biomarkers

• Biobanking

• Imaging

• Health and social outcomes

• Presymptomatic ND

What are the conditions that create a

ripe environment for innovation?

Joint Transnational Calls

One in 2011 for €16 M

Two in 2012-2013 for €29 M

Two in 2013-2014 for about € 30 M

Centres of Excellence in

Neurodegeneration (CoEN) program

2011 for € 6M ; in 2012-13 for € 8M

cold, orderly logic of “day science” and “night science” that wanders blind ...

hesitates, stumbles, recoils, sweats, wakes with a start. […] There is no way to

predict whether night science will ever become day science; whether the

prisoner will emerge from the darkness

«Of flies, mice and man» Francois Jacob

SRA Implementation (2012-2014)

Annual Calls for Proposals

Centres of Excellence in Neurodegeneration (CoEN)

Year Total fund

available

Research Area No. of Projects

2011(pilot)

€16M Optimization of biomarkers

+ harmonization of their use

4

2012 €18M Risk and Protective Factors 5

2012 €11M Evaluation of Healthcare 6

2013 €12M Cross-Disease Analysis 10

2013 €11M Pilot Preventive Strategies 5

2011 €6MPhase I : common resources and methodological

approaches8

2012-13 €8M Phase II : “Pathfinder” projects 5

Annual Call statistics

Year Call area of interest

No. of

proposals

submitted

Budget

requested

(million €)

No. of proposals

recommended for

funding

No. of

proposals

supported

Budget

supported

(million €)

Success

rate (%)

2011 Harmonization of Biomarkers 14 €31 5 4 €14 29%

2012 Risk and Protective Factors 52 €97 18 5 €17 10%

2012 Healthcare Evaluation 22 €29 9 6 €9 27%

2013 Cross-Disease Analysis 90* €112 23 10 €12.5 11%

2013 Pilot Preventive Strategies 35* €36 5 5 €7 14%

Total 213 €157m 60 30 €59.5m 18%

* pre-proposals

2015 Call for proposals

• January 2015 - Cofunded Call with the European Commission

• Three topics

• Longitudinal Cohort Approaches

• Advanced Experimental Models

• Risk/Protective Factors

• €30 million from Member States

• top-up of €10 million from European Commission

JPND-supported projects:

Risk and Protective Factors

• APGeM:

Pre-clinical genotype-phenotype predictors of Alzheimer’s disease and other dementia

Coordinator: Tormod Fladby, Akershus University Hospital and University of Oslo, Norway

• COURAGE-PD:

COmprehensive Unbiased Risk factor Assessment for Genetics and Environment in Parkinson‘s Disease

Coordinator: Thomas Gasser, University of Tübingen, Germany

• PERADES:

Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease using multiple powerful

cohorts, focussed Epigenetics and Stem cell metabolomics

Coordinator: Julie Williams, Cardiff University, United Kingdom

• RiMod-FTD:

Risk and Modifying factors in Fronto Temporal Dementia

Coordinator: Peter Heutink, German Center for Neurodegenerative Diseases – Tübingen, Germany

• STRENGTH:

Survival, Trigger and Risk, Epigenetic, eNvironmental and Genetic Targets for motor neuron Health

Coordinator: Ammar Al-Chalabi, King’s College London, United Kingdom

JPND-supported projects:

Pilot Preventive Strategies

• EURO-SCD:

Subjective cognitive decline in preclinical Alzheimer’s Disease: European initiative on harmonization and on a

lifestyle-based prevention strategy Coordinator: Frank Jessen, Germany

• MIND-AD:

Multimodal preventive trials for Alzheimer’s Disease: towards multinational strategies

Coordinator: Mia Kivipelto, Finland

• NEUROEXERCISE:

The effects of an extensive exercise program on the progression of mild cognitive impairment (MCI)

Coordinator: Stefan Schneider, Germany

• ONWebDUALS:

ONTology-based Web Database for Understanding Amyotrophic Lateral Sclerosis

Coordinator: Mamede de Carvalho, Portugal

• PreFrontAls:

Searching for therapeutic interventions in frontotemporal dementia with C9ORF72 repeat expansions in the

presymptomatic stage Coordinator: John C van Swieten, The Netherlands

JPND-supported projects:

Cross Disease Analysis

• CeBioN:

Cellular Bioenergetics in Neurodegenerative Diseases: A system-based pathway and target analysis

Coordinator: Maria Ankarcrona, Sweden

• CrossSeeds:

Mechanisms of pathogenic protein cross-seeding in neurodegenerative disorders

Coordinator:Hans-Ulrich Demuth, Germany

• DAMNDPATHS:

Elucidation of common transcriptional targets in vulnerable DopAmine, MotorNeuron and

frontotemporal Dementia disease PATHwayS Coordinator:Eva Hedlund, Sweden

• Fly-SMALS:

Common RNA-dependent pathways for motor-neuron degeneration in spinocerebellar muscular

atrophy and amyotrophic lateral sclerosis Coordinator:Jörg B. Schulz, Germany

• InCure:

Innate Immune Activation in Neurodegenerative Disease Coordinator: Michael T. Heneka, Germany

JPND-supported projects:

Cross Disease Analysis (cont’d)

• MisingLink:

Identification and structural characterization of the primordial cytotoxic conformers of the amyloidogenic

cascade: Ideal prevention/diagnostic/therapeutic targets in neurodegeneration

Coordinator: Mariano Carrión-Vázquez, Spain

• NeuroGeM:

Identification of genes that modulate the severity of all neurodegenerative diseases

Coordinator: Jörg Gsponer, Canada

• NeuTARGETs:

Targeting the propagation of pathogenic protein assemblies in neurodegenerative disease

Coordinator: Chiara Zurzolo, France

• PrPC&PDK1: The PrPC / PDK1 / TACE signaling axis at the cross-road of several aggregate-prone

protein-associated neurodegenerative diseases Coordinator: Benoit Schneider, France

• SynSpread:

Role and mechanism of alpha-synuclein and ataxin-3 spreading in Parkinson and Machado-Joseph

diseases. Coordinator: Luis Pereira de Almeida, Portugal

COEN

Funding Collaborations among Centers of

Neuroscience in:

Belgium, Germany, Ireland, Italy, Slovak Republic,

Spain, UK and CANADA

http://www.coen.org/projects.html

COEN Phase I (8 projects funded)

• Standards for determining the vascular contribution to neurodegeneration Joanna Wardlaw (MRC), Martin Dichgans

(DZNE), Dr Eric Smith (CIHR)

• Integrated approach to identify novel genes for frontotemporal lobar degeneration Marc Cruts (VIB), Christine Van

Broeckhoven (VIB), Christian Haass (DZNE), Dieter Edbauer (DZNE)

• Mitochondrial dysfunction and susceptibility to Parkinson’s disease: New models of pathogenetic interactions Donato A.

Di Monte (DZNE), David S. Park (CIHR), Fabio Blandini (MDS), Anthony H.V. Schapira (MRC)

• Early synaptic plasticity and network dysfunction in transgenic (tg) rat models of Alzheimer’s disease (AD) Michael

Rowan (HRB/SFI), Claudio Cuello (CIHR), Martin Fuhrmann (DZNE),Michel Goedert (MRC) and Stefan Remy (DZNE)

• Immune subtype in Parkinson disease Thomas Gasser (DZNE), Antonio P. Strafella (CIHR)

• C. elegans models of mitochondrial deficiency in the nervous system Daniele Bano (DZNE), Siegfried Hekimi (CIHR), Mario

de Bono (MRC)

• The GENetic Frontotemporal Dementia Initiative (GENFI): a new multi-centre platform for the study of frontotemporal

lobar degeneration Martin Rossor (MRC), Giovanni B. Frisoni (MDS), Mario Masellis (CIHR)

• Identification of generic supressors of proteinopathies David Rubinsztein (MRC), Joerg Gsponer (CIHR)

COEN - Phase II (5 projects funded)

• Targeting glucocerebrosidase for disease-modifying treatments in Parkinson’s disease Anthony H.V.

Schapira (UK), David Park (Canada), Donato Di Monte (Germany) and Fabio Blandini (Italy)

• WNT signaling: biomarker and target evaluation in Alzheimer’s disease Antonio Cuadrado (Spain),

James Woodgett (Canada) and Simon Lovestone (UK)

• Mechanisms of amyloid-β clearance in models of vascular cognitive impairment and mixed

dementiaGabor Petzold (Germany) and Danica Stanimirovic (Canada)

• In vivo neuronal cell reprogramming for a new regenerative approach in Parkinson’s diseaseVania

Broccoli (Italy), Alexander Dityatev (Germany) and Josè Luis Lanciego (Spain)

• microRNA as novel therapeutic targets and disease biomarkers in Alzheimer's Disease,

Frontotemporal dementia and Amyotrophic lateral sclerosis (NEURO-MIR)Jochen Prehn (Ireland),

Andre Fischer (Germany), Pierre Lau (Flanders), Jose Lucas (Spain)

Partnership with the EC

• Establish programme of co-investment to leverage the value of investments

and resources at both national and EC level, to the benefit of Europe

• Synergy between JPND actions and H2020 programme

• First call of Horizon 2020 (Dec. 2013)

• ERA-NET cofund: Implementing a transnational call with EU co-funding

• Three Call Topics in preparation for the end 2014/beginning 2015:

• Identification of genetic, epigenetic and environmental risk + protective factors

• Longitudinal cohorts in ND research

• Advanced experimental models of ND

Partnering with Industry

• Substantive participation in development of JPND Research Strategy

• Now Members of Scientific Advisory Board

• Ongoing discussions with EFPIA-IMI

• Enlarge the contacts (pharma, device, IT, diagnosis, imaging, welfare

technologies, AAL, …)

• JPND Industry Action Group to develop new public-private-partnerships

Keep up to date

• Visit the JPND website:

• http://www.jpnd.eu

• Sign up to the JPND News Feeds

• E-mail us: secretariat@jpnd.eu

• Follow us on Twitter:

@JPNDEurope

JPcofuND

Topic 1: Genetic, epigenetic and

environmental risk and protective factors

of neurodegenerative diseases (1/3)

It is important to better understand the genetic,

epigenetic and environmental factors that underlie

an individual’s risk and resilience, the triggering

events leading to illness, the relationship and

interplay between these factors and their relative

importance, and the role of potential environmental

and behavioural modulators.

Genetic, epigenetic and environmental

risk and protective factors of ND (2/3)

• identification of underlying genetic variability in neurodegenerative diseases,

using cutting edge technologies, e.g., exome and genome sequencing,

• regional and temporal mapping of the transcriptome, proteome and epigenome

of the human brain as it relates to aging and neurodegeneration,

• studies to explain phenotypic variability of the neurodegenerative process

including the role of gender and the reasons for and the impact of the variable

age of onset,

• unravelling the mechanisms by which (recently identified) risk genes contribute

to the development of neurodegenerative diseases,

• understanding the interplay between genetic and environmental factors, for

instance by developing new tools and approaches to identify and quantify

environmental risk for neurodegenerative disease, and the effective integration

of new genetic and molecular assessments e.g., within existing cohorts,

• identification of environmental and behavioural modulators of ageing and

neurodegeneration in order to ultimately determine protective and resilience

factors. Such modulators may include, but are not limited to, nutrition, diet,

caloric intake, physical activity, anthropometric and adiposity parameters,

sleep habits, social activities and social networks or interactions, intellectual

activities, educational and professional attainments, leisure activities and

other lifestyle factors,

• identification of genetic factors that protect against the development of

neurodegenerative diseases.

Genetic, epigenetic and environmental

risk and protective factors of ND (3/3)

Topic 2: Longitudinal cohort approaches

in neurodegenerative diseases (1/2)

Current population and disease-focused human cohorts offer

significant opportunities for advancing our understanding of the

risks of developing neurodegenerative conditions and the

influences on disease progression. Such cohorts also offer the

prospect of providing platforms for prevention and intervention

studies in the longer term.

Longitudinal cohort approaches in

neurodegenerative diseases (2/2)

Successful proposals are expected to have one or more of the following

characteristics :

• brings together well-characterised relevant cohort groups to harmonize, or

make accessible, data to promote secondary analysis,

• adds new measurements, sample collections or data sweeps that add

significant value or provide linkage to other studies,

• establishes novel assessment measures, taking advantage of new

technologies, extending beyond the cognitive domain (i.e. motor and

perceptual function) that can be applied to the broad spectrum of

neurodegenerative diseases, or

• delivers methodological developments or enhancements to establish cohorts

as intervention platforms.

Topic 3: Advanced animal or cell

experimental models of ND (1/3)

Supporting the creation of novel experimental models that are more

predictive of disease

A number of elements of complexity must be taken into account when

modelling a human neurodegenerative disease:

Genetics: causative mutations and common variants increasing the risk for

sporadic forms of neurodegenerative diseases,

Environment: environmental toxins, stress, social interactions, infections,

nutrition,

Aging: dysmetabolism, hormonal factors, accumulation of damaging insults,

genomic instability, immune derangement.

Advanced animal or cell experimental

models of ND (2/3)

• investigation of phenotypic heterogeneity by analysing cell death processes, cell

physiology and pathology,

• development, testing and validation of models mimicking specific symptoms that

do not respond to current treatments,

• development, testing and validation of standardized phenotypic readouts,

• monitor disease onset and progression using novel or established biomarkers

relevant to the human diseases and clinical settings,

• characterization of progressive neurodegeneration and protein aggregate

deposition/propagation,

• thorough investigation of the relationship between risk and protective factors

and genetic determinants,

Advanced animal or cell experimental

models of ND (3/3)

• establishing high-throughput screening of factors influencing

disease risk and innovative drugs,

• implementation of innovative imaging techniques,

• gaining a deeper understanding of proteotoxicity mechanisms,

• further understanding the role of neuroinflammation,

• developing standards for harmonizing functional tests, phenotypic

readouts or the use of models in different centres.