Template for the submission of a proposal for a by ygq15756

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IRELAND

Resolving Disorders of Chronic Inflammation Across Europe: Detection,
Intervention and Prevention

1. Theme for the Joint Programming Initiative
Inflammation is a familiar ally in helping us fight infection. However, almost all ailments that afflict
people of developed countries, including those of the EU, are fundamentally disorders of
inflammation. Some are well known; the crippling inflammation that affects the joints of
rheumatoid arthritis sufferers, for example, results from persistent attack by the body’s own
immune defences. Similarly, inflammatory bowel disease (IBD) results from inappropriate and
severe responses of our immune systems to gut bacteria.

Inflammation is also at the core of many more prevalent conditions and across Europe,
atherosclerosis is perhaps most familiar. This is a complex disorder, exacerbated by environment,
lifestyle and genetic factors resulting in an inflammatory deposition on blood vessel walls and
ultimately in coronary artery disease. Obesity too has an underlying inflammatory component,
with adipose and fat tissue harbouring large numbers of inflammatory cells. With obesity now
reaching epidemic proportions in many countries, there is growing appreciation of the enormity of
its impact on metabolism and its multiple unwanted downstream consequences, including type-2
diabetes. Among the many other conditions with an underlying inflammatory component or
origins are neurodegenerative disorders, such as Alzheimer’s disease, a range of allergies,
pulmonary disorders and cancers.

        Major problems
       Significant increase in inflammatory disorders in the past 20 years across all
        member states (obesity reaching epidemic proportions)
       Many of the disorders if left unchecked have the potential to trigger major
        economical burden due to illness and premature death.
       Current research efforts are fragmented and don’t include a societal-clinical-
        scientific framework

As distinct as these diseases are, they share many of the same key mechanisms of inflammation.
The principal aim of this joint programming proposal is to achieve a cohesive European approach
to understanding the similarities and differences in inflammatory processes across broad sectors
of disease. In so doing, joint programming would to bring together the strands of research, clinical
expertise and therapeutic approaches and approaches of different healthcare systems.

When considered together, inflammation-based diseases continue to present a growing problem
of immeasurable socio-economic proportions. Research funding invested by individual nations
each year into the fundamental aspects of inflammation are considerable; Focus is intensive at
the molecular and cellular levels, as well as in how this applies to the broader pathophysiology of
a diverse array of diseases. Importantly, considerable research dollars and Euros are also spent
in untangling the complex risk factors and genetic associations that underpin many conditions and
diseases.


        PRIMARY GOALS
       A classification of key those factors (societal, environmental, genetic) that increase
        inflammatory disease onset
       Improved understanding of key inflammatory pathways across diseases, shared and
        distinct mechanisms.
       Development of diagnostics and medical devices that allow for early diagnosis
       The development of drugs and therapeutics that will promote recovery
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2.       Proposing GPC member/members

Ireland and

3.       Objectives
The proposal recognises three broad themes underpin the challenge posed by inflammatory
diseases collectively representing significant social, clinical and scientific challenges.

     1. Detection- Improved detection of common and distinct pathways of pathways will build on
        capacity in basic research in common mechanisms of inflammation, genetics of disease
        susceptibility, biosensors and population and individual level monitoring of disease and of
        inflammation.

     2. Intervention – Through a more comprehensive investigation of the inflammatory
        responses associated with the disease sectors at basic scientific and clinical levels, the
        mechanisms of the disease will be identified. Effective treatments and interventions for
        chronic inflammatory diseases remain a priority and outputs from basic and clinical work
        will help identify targets and new therapies developed. In addition, effective intervention
        will explore new modes of drug formulation and delivery.

     3. Prevention- Ultimately, the premise is that many of inflammatory diseases are
        preventable, with changes to lifestyles and improved understanding of risk factors making
        a significant difference. The prevention of disease in the first place must always be a
        chief goal, but realistically cannot be pursued in the absence of better understanding of
        disease mechanisms, risk factors, genetics, pathophysiology and diagnosis culminating
        from objectives 1 and 2.
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4.   Research Questions To Be Addressed
The programming research questions will focus on better detection across two broadly defined
disease sectors: gastrointestinal disorders and obesity and metabolic diseases. The overarching
concept is that with shared and distinct mechanisms of inflammation underlying each disease, a
comparative approach to understanding their genetics, distinct and common inflammatory
pathways and pathophysiology will ultimately lead to more accurate detection and early diagnosis.
Thus, uniting the two disease sectors are the common goals of detection, intervention and
prevention. The disease areas affect EU countries differently and variation will also exist in the
strengths and capacity between member states in the priorities of basic research, medical care
and initiatives aimed at improving lifestyle and environment. For this reason, it is anticipated that
a JPI in this area would have particular benefits in drawing the priorities and relative strengths of
different contributing members together in a productive and effective manner.




           Obesity                   Prevention
             and                      Detection                       Gastro-Intestinal
          Metabolic                                                      Disorders
          Disorders                  Intervention




4.1 Obesity and Metabolic Disorders
4.1.1 Chronic Inflammation and Obesity
In recent years it has become evident that inflammatory responses play a central role in obesity
and its associated disease states (type II diabetes, atherosclerosis). Our body’s adipose tissue
provides a flexible storage depot for excess nutrients, in addition the adipose tissue is also
responsible for the release of cytokines that regulate energy within the body. However, when the
adipose tissue’s ability to store lipid and regulate nutrient metabolism becomes imbalanced due to
the presence of excess nutrient inflammatory marker expression increase, initiating an
inflammatory response.

In the US a study on childhood obesity identified a dramatic rise in the prevalence of obesity in the
space of two decades, from about 5% in 1980 to 20% in 2000. What was also noted in this study
was that that during this same time period allergic response to skin tests has almost doubled in
children from 22% to 42% in children. Visness et al examined the results from the National Health
and Nutrition Examination Survey 2005-2006 in the US and identified that.
        Allergies were more prevalent among obese and overweight children.

        Obesity was associated with chronic inflammation.

        Allergy was also associated with inflammation.
Our understanding of complex relationship between inflammation, obesity and disease
progression is still very much in its infancy and the research in this area requires a coherent
structured approach considering the scale of the problem (see below).
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Why does Obesity require a Joint Programming Approach?
The prevalence of obesity is currently on the rise in almost all industrialized countries and has
become such a prominent problem that many countries have set up national taskforces (Ireland,
Australia, Greece, UK), in addition to the already established international obesity task force
(IOTF http://www.iotf.org/index.asp). The most worrying statistic is that childhood obesity has
reached epidemic proportions in Europe, with body weight now the most prevalent childhood
disease. In a 2005 EU platform paper on obesity, the Mediterranean islands of Malta, Sicily,
Gibraltar and Crete as well as the countries of Spain, Portugal and Italy reported overweight and
obesity levels exceeding 30% among children aged 7-11. In addition England, Ireland, Cyprus,
Sweden and Greece report levels above 20%, while France, Switzerland, Poland, the Czech
Republic, Hungary, Germany, Denmark, Netherlands and Bulgaria reported overweight levels of
10- 20% among this age group. In Ireland there is thought to be in the region of 300,000
overweight and obese children with this number rising by a rate of over 10,000 per year. In
Europe this rate of increase is thought to be in the region of 400,000 children per year.

Because obesity is associated with premature death, excessive morbidity and serious
psychosocial problems the damage it causes to the welfare of citizens is extremely serious and for
this reason a concerted intervention is necessary and warranted. In 2009 it is believed that 2,000
premature deaths in Ireland will be attributed to obesity with this number set to rise in future years.
In addition to the in care hospital costs, obesity results in many indirect costs such as days lost to
the workplace due to illness arising from obesity and output foregone as a result of premature
death and this is estimated to cost Ireland alone approximately €4 billion per year.

4.1.2 Type II Diabetes
Obesity is a major risk factor for the development of type II diabetes. Type II diabetes accounts for
approximately 90% of cases of diabetes and is characterised by insulin resistance in combination
with dysfunction of insulin producing cells. Insulin is a hormone produced by the pancreas that
plays an essential role in regulation of blood sugar levels. Individuals with diabetes fail to make
insulin (Type I diabetes) or to respond to it (type II diabetes) resulting in elevated blood glucose
levels. Long term complications of diabetes include damage to the blood vessels, eyes, kidneys,
and nerves. Early diagnosis and appropriate management, such as increased exercise and
dietary modification, is essential to reduce the occurrence of these complications.

Chronic low grade inflammation underlies the pathogenesis of type II diabetes and circulating
markers of inflammation, such as IL-6 and C-reactive protein (CRP), are strong predictors of
development of the disorder. Many of these inflammatory markers, such as CRP, are also shared
with CVD and it is now believed that activation of inflammation is a common antecedent to both
Type II diabetes and CVD. Patients with Type II diabetes are at an increased risk of developing
CVD. The exact effect of these inflammatory markers on glucose metabolism is still unclear but it
is clear that cytokines such as IL-6 and TNF can directly interfere with insulin signaling. Early
studies also indicate that anti-inflammatory drugs, such as salsalate, may help prevent type II
diabetes.

Why does Type II Diabetes require a Joint Programming Approach?
We are currently in the midst of a diabetes epidemic. The International Diabetes Foundation has
estimated that the number of people affected will increase by more than 50% in the period from
2003-2025, with a predicted 333 million people affected by 2025. Both industrialized and
developing countries will be affected. In the US prevalence rates have doubled between 1990 and
2005 and the Centre for Disease Control (CDC) has characterized the increase as an epidemic.
Within Europe an increase from 7.8% to 9.1% (58.1 million persons) is predicted. In a study by the
International Diabetes Federation-European Region (IDF-Europe) and the Federation of European
Nurses in Diabetes (FEND), the prevalence of diabetes is predicted to rise from 7.5% to 16% over
the next 20 years with an increasing prevalence of Type 2 diabetes being the main driving force
behind the increase. In the Republic of Ireland, the WHO estimated that in 2000 there were
86,000 cases of diabetes with the number of cases expected to rise to 157,000 by 2030. In 2005,
141,063 adults in the Republic of Ireland (4.7%) had diabetes (diagnosed or undiagnosed).
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Type II diabetes has traditionally been considered an adult disorder. However, the prevalence of
this disorder within children is particularly on the rise, in parallel to rising obesity rates and altered
dietary and life style factors during childhood. Genetic factors also interact with these
environmental factors to determine the overall individual risk of developing the illness. A greater
understanding of the causative genetic factors will reveal the mechanistic basis of this metabolic
disorder. This JPI is therefore timely and will build upon the recent large scale genomic studies to
develop new diagnostics and therapies.

4.1.3 Ireland’s Contribution to Research in the Area of Obesity and Metabolic Diseases
Ireland has set up a national task force to specifically address the issue of obesity and related
disorders and in doing so have identified the scale of the problem that the will face if the spread of
the disease is left unchecked. To this end an evaluation of the population, their diets, lifestyles
and social settings is beginning to identify communities, population clusters and individuals that
are at most risk of becoming obese and thus having the secondary development of type-II
diabetes and other secondary disease.

At a basic research level Ireland has invested approximately €10 million in this past ten years in
basic and clinical research in projects mainly focused on the characterization of specific problems
associated with diabetes (diabetic nephropathy, diabetic retinopathy, circulation) and the
development of diagnostics (Prof Holthofer DCU). From the economic burden described above
then it is readily apparent that as a nation there is a significant under spend in research within
these areas. Ireland does have specific expertise in certain areas, however, we do not have the
capacity to effectively combat a problem of an epidemic proportion.

4.2 Gastro-Intestinal Inflammatory Disorders
The mucosal immune system of the gastrointestinal tract (GI tract) plays a key role in preventing
pathogens from entering the body and maintaining the delicate balance with the gut micro-flora.
Inappropriate activation of the mucosal immune system contributes to the development of a
number of chronic inflammatory disorders, such Inflammatory Bowel Disease (IBD)

4.2.1 Inflammatory Bowel Disease
Crohn’s Disease (CD) and Ulcerative Colitis (UC), collectively known as Inflammatory Bowel
Disease (IBD), are chronic inflammatory disorders of the intestine resulting in symptoms such as
abdominal pain, diarrhea, vomiting or weight loss (CD) or constant diarrhea mixed with blood, of
gradual onset (UC). Treatment options are restricted to controlling symptoms, inducing remission
and preventing relapse although UC can be cured by surgical removal of the colon. Years can
elapse prior to accurate diagnosis of IBD and given increased risk of bowel obstruction,
malnutrition and cancer, early detection is crucial.

The underlying pathophysiology of IBD remains to be elucidated. However, it is likely to involve a
complex interplay between genetic, microbial, and environmental factors resulting in a sustained
activation of the mucosal immune system and chronic inflammation/tissue damage. Genetic
changes responsible for conferring susceptibility are currently under investigation. DNA variants in
the NOD2/CARD15 gene, which has known functions in bacterial recognition, apoptosis and
inflammatory signaling, look promising. Environmental triggers may include improved hygiene and
reduced exposure to intestinal pathogens in addition to cigarette smoking, all of which may affect
development of the humoral immune system. Indeed, it is believed that the fundamental defect in
IBD is an overactive mucosal immune system which, in genetically susceptible individuals,
inappropriately reacts to normal constituents of the mucosal microflora.

Why does IBD require a Joint Programming Approach?
IBD affects 15,000 people in Ireland, 130,000-140,000 people in the UK and millions worldwide.
The incidence (annual diagnosis rate) of CD varies from 0.5-24.5/100,000 inhabitants with
prevalence rates (estimated rate of population affected) as high as 396/100,000 inhabitants. IBD
is an important public health problem as it afflicts young people, typically females in their child
bearing years, and has a protracted and relapsing clinical course.
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The prevalence of IBD has been steadily increasing in the US and Europe over the past 20-50
years (Juillerat et al. 2008, Armitage et al. 2001, Jacobsen et al. 2006) with rises as much as 30%
reported. The rising prevalence of IBD may be a feature of developing nations or urbanisation and
a recent report suggests that eastern European countries are now experiencing increasing
incidence rates for both CD and UC (reviewed by Lakatos and Lakatos, 2009). In Europe, CD has
now become one of the commonest chronic diseases. Since it mainly affects young adults and
has a chronic and progressive course, this disease presents a significant social and economic
burden. In terms of health care costs, a recent German study estimated mean 4-week costs per
patient of €1425 and €1015 for CD and UC, respectively (Stark et al. 2006). The cost of IBD to the
NHS has been estimated at about £720 million per annum, based on the prevalence and an
average cost of £3,000 per year per patient. These lifelong healthcare costs are comparable to
those for major chronic disorders such as cancer and diabetes. There is currently no cure for CD
and early detection is critical to prevent further pathology, associated disorders, such as colorectal
cancer, and increased mortality.

4.2.2 Celiac Disease
Celiac disease in an inherited autoimmune disorder triggered by the digestion of gluten resulting
in an inappropriate immune response against the small intestine, resulting in chronic inflammation
and inhibition of absorption of important nutrients. Patients typically present with chronic
diarrhoea, weight loss and anaemia, in addition to extra-digestive symptoms, such as infertility
and skin lesions. However, many patients are actually asymptomatic. Such a variable
presentation has resulted in difficulties diagnosing this chronic disorder and it is estimated that
only 10-20% of cases in Europe and the US have been diagnosed. Early diagnosis is essential to
reduce patients’ risks of developing other autoimmune disorders, neurological problems,
osteoporosis and cancer in addition to increased mortality. A gluten-free diet is currently the only
form of treatment.

Celiac disease is a multi-organ inflammatory disorder of multi-factorial aetiology. Familial studies
have revealed a genetic basis for this disorder and the human leukocyte antigen (HLA) class II
DQA and DQB genes are the principal determinants of genetic susceptibility. These genes
encode products that are responsible for presenting gluten (environmental trigger) to immune
cells.

Why is celiac disease of significant concern?
An estimated 2.5 million Europeans suffer from celiac disease (approximate prevalence of 1%).
However, this figure is on the rise. For example, a recent population-based cohort study in Finland
reported a doubling in prevalence in the last two decades, which now stands at 2% (Lohi et al.
2007). This disorder is a major public health problem because of its high prevalence and long-
term complications. Patients can be affected at any age, including during childhood, resulting in a
considerable life long disease burden. Furthermore, patients are at an increased risk of
developing other autoimmune disorders, such as Type I Diabetes, systemic lupus erythmatosus,
and rheumatoid arthritis in addition to risk of seizures, short stature and cancer.

Accurate diagnosis is one of the major challenges facing patients and physicians. The disorder
can be very difficult to diagnose which has resulted in a low level of detection. Intestinal biopsy
remains the gold standard for diagnosis, although serological tests of varying sensitivity and
specificity are available. Adherence to a strict gluten-free diet, the only form of “treatment”
available to patients, is extremely difficult as gluten is present in many foods as an additive or
contaminant. The long-term consequences of a gluten-free diet are also unclear. Furthermore,
gluten-free foods have poor availability and are more expensive than their gluten-containing
counterparts. These issues significantly impact on dietary compliance and the quality of life for
sufferers of celiac disease.

CDEUSSA is a specific support action from FP6 that aims to identify the major issues in the areas
of treatment, prevention and public health in the area of celiac disease. A number of stakeholder
events have been held resulting in prioritization of the following areas: development of primary
prevention and new treatment strategies for celiac disease in addition to revised diagnostic criteria
(Troncone et al. 2008). This JPI can build upon the foundations laid by this EU initiative.
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4.2.3    Ireland’s Contribution to Research in the Area of Gastro-intestinal Inflammatory
         Disorders
This JPI will build upon existing strengths in Ireland in the areas of inflammation, GI disorders and
diagnostics. SFI has invested over €70 million in inflammation and GI disorders and approximately
€38 million in diagnostics and biosensors. This investment has resulted in the development of a
number of world class research centres in highly relevant areas, such as the Immunology
Research Cluster, Alimentary Glycoscience Cluster, Alimentary Pharmabiotic Centre in addition to
the Biomedical Diagnostics Institute and a number of nanotechnology research centres. Ireland
also has a number of indigenous companies in the medical diagnostics sector. Therefore, Ireland
is well placed to lead the development of diagnostics for early detection of chronic inflammatory
disorders and to maximize the impact of the investment in this area to date.

4.3      Overview of Ireland’s Contribution to Research in the Area of Chronic Inflammation
Immunology has emerged as an area of significant research strength in Ireland over the last ~10
years, partly due to funding from SFI and the HRB. SFI has awarded more than €70 million in
grants to world class Irish researchers investigating inflammatory disorders of the respiratory and
gastrointestinal tracts in addition to studies of host-microbe interactions, which as highlighted
earlier, play a crucial role in normal development of the immune system. In addition to a large
number of Principal Investigator awards, we have funded a number of highly relevant clusters of
academic and industrial researchers under our Centres for Science, Engineering and Technology
(CSET) and Strategic Research Cluster (SRC) programmes which would provide important
building blocks for this JPI.

The Immunology Research Cluster (IRC SRC) led by Prof. Kingston Mills and based in Trinity
College Dublin has been awarded €7.5 million to investigate and exploit the interface between the
innate and adaptive immune system. This cluster of researchers specifically aims to develop anti-
inflammatory agents to treat autoimmune disorders and has developed a number of collaborations
with industry to achieve its aims (e.g. Opsona Therapeutics, Scherring Plough).

The Alimentary Glycoscience Research Cluster was founded in 2009, under the lead of Prof.
Lokesh Joshi under the SFI SRC programme (€5.1 million award). The aim of this cluster is to
investigate the glycomic responses of gut cells to pathogenic and probiotic microorganisms and
milk oligosaccharides and is comprised of leading researchers from universities throughout the
republic of Ireland.

The Alimentary Pharmabiotic Centre (APC, CSET), led by Prof. Shanahan at University College
Cork, has received €38 million from SFI and aims to investigate the means by which intestinal
bacteria influence health and disease and develop new therapies for lifelong debilitating
gastrointestinal diseases such as gastroenteritis, ulcerative colitis, and Crohn’s disease. To help
achieve these aims, APC have developed industrial collaborations with Alimentary Health and
GlaxoSmithKline. Alimentary Health developed AlignTM, the only probiotic currently on the market
that demonstrates efficacy in the treatment of Inflammatory Bowel Syndrome.

Ireland has also developed significant research strengths in the area of medical
devices/diagnostics and SFI actively funds research in the area of biosensors and diagnostics (in
excess of €18.5 million to date) under many of our award programmes, including CSET. In
particular, the Biomedical Diagnostics Institute led by Prof. Brian McCraith was funded under our
CSET programme in 2005. The BDI is a multidisciplinary research institute focused on the
development of next generation point-of-care biomedical diagnostic devices.

Ireland has also made significant funds in regenerative medicine with obvious implications for
therapies in inflammatory disorders. In particular the Regenerative Medical Institute SFI funded
CSET based in the National University of Ireland Galway has interests in regenerative capacity of
adult stem cells to in diseases with strong inflammatory components, including cardiovascular
disease and osteoarthritis.
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Ireland has significant research strengths in the areas of immunology and biosensors/biomedical
diagnostics in both the academic and industrial sectors. SFI have funded two CSETs and 2 SRCs
and a large number of principal investigators in areas relevant to this JPI. Some examples are
listed below:

Principal Investigator          Research Focus
Cormac Taylor (UCD)             Intestinal models of drug uptake and delivery/Developed a drug
                                for IBD in collaboration with Sigmoid Biotechnologies
Lothar Steidler (APC/UCC)       Development of genetically engineered Lactococcus lactis that
                                secrete bioactive cytokines/Clinical trial for treatment of IBD
Christine Loscher (DCU)         The role of dietary fatty in modulating Th1-mediated disease
Jakki Cooney (UL)               Role of bacterial proteases in gut health and disease
Brendan Loftus (UCD)            Genomics of host-microbe interactions
Luke O’Neill    (TCD)           Innate immunity and inflammation

4.4     Overview of Ireland’s Contribution to Research in the Area of Diagnostics
Ireland has also developed significant research strengths in the area of medical
devices/diagnostics and SFI actively funds research in the area of biosensors and diagnostics (in
excess of under many of our award programmes, including CSET. Ireland has also recognized
strengths in nano-technology applications for the Life Sciences sector with possible uses in the
development of diagnostics and sensors (in excess of €20 million SFI investment).

Diagnostics
The Biomedical Diagnostics Institute (BDI: http://www.bdi.ie/) led by Prof. Brian McCraith was
funded under our CSET programme in 2005 (€16.5 million investment with €6.5 million investment
from industry partners). The BDI is a multidisciplinary research institute focused on the
development of next generation point-of-care biomedical diagnostic devices for monitoring
indicators of chronic diseases, including self-test, home use. There are 6 core industrial partners
involved with BDI including Becton Dickinson and Co., Analog Devices Inc. and Enfer
Technologies Inc. Ireland also has a number of home grown companies with a focus on
diagnostics, such as Biotrin and Trinity Biotech.

Biosensors
Expertise in the area of biosensors includes Prof. John Lowry (National University of Ireland at
Maynooth) who is developing sensors and biosensors to develop neurochemicals in the living
brain, technological developments which could be also applicable to chronic inflammatory
disorders. The Technology Research for Independent Living (TRIL: http://www.trilcentre.org/)
research centre, which aims to assist older people in living from home, is developing the
technology required for remote sensing. We also have significant expertise in the application of
nanotechnology/nanoscience to the development of biosensors (see below).

Nanotechnology
Ireland is noted for its significant strengths in nanotechnology and nanoscience. A number of
world class research centres devoted to research in these domains have been established, such
as the CRANN nanoscience research centre, Tyndall and the BioNanoInteract Strategic Research
Cluster. The CRANN centre has a research programme focused on development of bio-nano-
sensors of relevance to medical diagnostics and imaging devices and has built industry
partnerships with major multinationals, such as Intel and Hewlett Packard. Strengths in the nano-
technology development and characterization of nano-materials, with potential uses in medical
diagnostics, include the Tyndall research centre, and a cluster of researchers based at University
College Dublin (UCD). This cluster includes Prof. Suzi Jarvis (Nanoscale Function group), Prof.
Gill Lee (BioNanoTechnology research group with a focus on development of lap-on-a-chip
devices) and the Centre for BioNanoInteractions (http://www.cbni.eu/), one of the world's leading
Centres of Knowledge in bionanointeractions applied to the fields of nanosafety, nanobiology and
nanomedicine. This centre was funded through the SFI SRC programme.
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4.5     Timescales and Targets for JPI on Chronic Inflammatory Diseases

Detection 2013 onwards: A 3 – 4 year period would is envisaged for us to begin to generate
medical devices and diagnostics that could accurately detect the early development of many of
the disease states. A further 2 years may be required for the development of these into
commercially available, easy to use kits that can be widely used either at home or under the
supervision of medical practitioners.

Intervention 2014 onwards – The effective treatment of chronic inflammatory diseases will come
form a better understanding of disease mechanisms. Given that even if we identify drugs with
great potential at a very early stage these compounds therapeutic strategies will require a very
detailed characterization before they can be widely used.

Prevention 2011 onwards: Programmes and initiatives that tackle the prevention of diseases
might be envisaged begin almost immediately. It is hoped from the collaborating of large scale
epidemiological data from each of the participating states within this JPI that we would be able to
clearly establish those societal, environmental and genetic factors that are of greatest significance
for an increased prevalence of each of the disorders within various sub populations.


                                 Milestone Time line

          2011        2012        2013        2014       2015         2016        2017
                                       Detection
                      Markers, Mediators, Devices and Diagnostics
                         (e.g. prototype diagnostic kits for Type-II diabetes)
                                                           Intervention
                                                      Drugs and Therapeutics
                                                       (e.g. 1st phase clinical trials)
                     Prevention
             Risk factors and Education
 (e.g. structured education on health for school children)


5.      Added-Value, Benefits and Impact
Benefits and impact of a JPI under the proposed theme for European citizens and European
competitiveness as well as other benefits JP approach might bring to addressing the proposed theme.
The value added to overall current research financed from national and Community public funds and
its potential to increase the efficiency and impact of public R&D financing.

Inflammation research and immunology have emerged as areas of significant research strength in
Ireland over the last ~10 years. SFI has awarded more than €80 million Euro in grants to world
class Irish researchers investigating inflammatory mechanisms of relevance to obesity, metabolic
and GI disorders, in addition to studies of host-microbe interactions, which play a crucial role in
normal development of the immune system. As well as a large number of Principal Investigator
awards, we have funded many highly relevant clusters of academic and industrial researchers
under our Centres for Science, Engineering and Technology (CSET) and Strategic Research
Cluster (SRC) programmes. This substantial investment by national agencies has created a group
of world class research immunology researchers in Ireland. The proposed JPI would maximize the
current investment by coordination of Irish researchers towards a common grand EU challenge.
This would not only result in a more focused and aligned research strategy, but would also allow
Irish researchers even greater access to areas of expertise that are not particular strengths in
Ireland. Equally, the capacity of Ireland in this area would represent an important contribution to
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inflammation-based research in other countries in the EU. Ultimately, this will result in more
efficient and productive research programmes, with a greater potential impact from public R&D
spend.

Is this a problem that really requires a long-term sustained effort/investment with political
buy-in to effectively tackle it?
If the inflammatory disorders detailed above (obesity, type-II diabetes, Crohn’s disease, and celiac
disease) were specific to a single nation then a more specialized approach may be required. The
fact that the majority of these disorders are increasing across the EU and in much of the
industrialised world is itself indicative of the requirement for a JP in this area. When the term
epidemic is used in relation to childhood obesity, and the figures considered across the EU , the
percentage of the young population that are considered obese reveal themselves in frightening
proportions. The broader socio-economic burden to broader society including the workforce is
equally disturbing.

Currently, many of the major questions addressed above cannot be effectively answered at a
national level due to fragmented scientific and clinical research activities. Therefore, a clear
cohesive and international approach is required. This would allow specialised scientists, clinicians
and epidemiologists within each of the disease areas to combine their efforts to effectively reduce
the incidence of the disease, provide effective diagnostics and more effectively treat the disorders,

Is this a problem that really requires a long-term sustained effort/investment with political
buy-in to effectively tackle it?
Strong evidence shows that many of the inflammatory disorders and especially those discussed in
this proposal are on the increase, with the most striking rise occurring in the female population.
The area of obesity has received a major political buy-in already, with many countries setting up
national task forces to deal with the problem. Therefore, there is an apparent realisation at a
political level that the societal and economic burden of these disorders in the future is on a
dangerous trajectory. This can only serve to strengthen the argument for a sustained
effort/investment to effectively tackle the problem at an EU level is required.

6. Preliminary suggestions concerning the governance and implementation
State the level of the envisaged involvement of the participating countries. Provide preliminary
suggestions on the common vision, governance structure and the implementation of the proposed JPI.
Such information could include, among others:

Envisaged participation
Recognising the investments already being undertaken members states in research related to
these disease areas, participation would aim to most effectively link national research
programmes in basic inflammation research and those related to the specific disease areas. It is
recognized that the states will have different priorities in disease areas, and different levels of in
terms of programmes for diagnosis and treatment as well as potential national programmes in
disease prevention.

Governance and management
Ireland has taken an active role in the pilot JPI on Alzheimer’s disease and we would support a
similar structure (outlined below) being adopted for the current JP. The management structure
would be composed of: the Management Board, an Executive Board, a Scientific Advisory Board
and a Secretariat.
The Management Board will from the primary decision making body and will seek advice from the
Scientific Advisory Board on the Strategic Research Agenda and related matters. The Executive
Board will support the Management Board in all aspects concerning the preparation and
implementation of decisions. The Secretariat will organize the day to day management of the
management structure and implement those tasks assigned to it by the Management Board and
the Executive Board. Any Member State of the EU (MS) or any State associated to the European
Framework Programme (AS) willing to participate in the JPI can be represented with all
participating States represented in the Management Board. The membership of those States
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joining the Initiative later than the constitutive meeting shall be approved by the Management
Board.

If more than 10 countries wish to participate in the JP, an Executive Board shall be established
among the members of the Management Board and its mission will be to assist

  -   To assist the Management Board by preparing meetings, proposals for actions and
      strategy, allowing the Management Board to focus on strategic decisions.
  -   To ensure proper implementation of the Management Board decisions and to monitor
      follow-up of the action lists established by the Management Board
  -   To oversee the work of the Secretariat and specify the tasks to be carried out by it

The tasks of the Executive Board will be specified by the Management Board and the Executive
Board will report on a regular basis to the Management Board.

The Scientific Advisory Board shall assist the Management Board in establishing the Strategic
Research Agenda (SRA), and propose scientific priorities based on societal needs and scientific
evidence. It shall support the management board activities to implement the SRA according to a
realistic timeline.

In consensus with the Executive Board and with the help of the Secretariat, the Scientific Advisory
Board may invite collaborative ad-hoc working groups of experts and/or relevant stakeholders
were necessary to support them in their tasks.

How might this JPI work?
To ensure success, a JP on chronic inflammation would require a transparent and open
agreement between all member states to allow for the rapid transfer of knowledge between
sectors. In particular, to effectively reduce the prevalence of these diseases, any large scale
epidemiological studies covering societal, environmental and genetic factors will be coordinated.
Identify those sub population of individuals and educate/treat them effectively.

Approximate duration of the research activities;
In order for the JPI to be effective an initial extensive 5 year programme will be required to target
many of the inflammatory disorder outlined above. Following this initial 5 year period it would be
hoped that a significant proportion of the research studies could be significantly reduced as it
would be hoped that many of our major goals would be achieved in that time period. However, in
order to see an effective return on the initial investment a continuation of the JP would be
envisaged for a further 10 -15 years in order to establish if the measures taken are effectively
reducing the prevalence of many of the disorders

Openness to additional participant countries at a later stage, taking into account the
principle of open access as referred to in paragraph 7 of the Council conclusions
Openness and inclusion is a necessity for the success of this JP and as many member states as
possible would actively be encouraged to participate in this JPI. Chronic inflammation and the
associated disorders is a serious problem in all the EU member states as highlighted above.
Therefore a coherent and concerted effort is required to address the many issues relating to the
increased prevalence of inflammatory diseases and their mechanism’s of action. In taking action
now we can reduce the significant health and economic burdens that will undoubtedly affect the
EU member states in the not very distant future if no action is taken.

								
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