In this issue:

Welcome to Issue 4 - February 2010
Appointment of Dr Marina Zvartau-Hind as a Director of MMI
MMI Technology Platform Web-Portal is now live
Molecular Medicine Ireland - Review of 2009 and Forward Look
MMI welcomes Government's Plan for Health Research
Record attendance at MMI Techniques & Strategies in Molecular Medicine course
ICRIN pilots Research Readiness Programme
MMI Guidelines for Standardised Biobanking - Consultation Phase
Pilot Common Ethics Form now available
Molecules to Medicines course and workshop gives insight into biopharmaceutical industry
MMI Clinician Scientist Fellow involved in ground-breaking breast cancer research
MMI Course - Human Disease Genomics: SNPs, GWAS and Next-Gen Sequencing
Irish involvement in BBMRI, one of the ESFRI Biomedical Sciences Infrastructures
News In Brief
Upcoming Events

Welcome to Issue 4 - February 2010

Dr Damian O’Connell, Vice President for Clinical Research with Pfizer and Chair of Molecular Medicine Ireland spoke at the IPPOSI Strategic Forum on Clinical Research in November 2009 about the changes in the way the pharmaceutical industry funds clinical research and what Ireland has to do to become a core site for clinical trials. This is what he had to say.

Why Pharma is changing the way it funds clinical research

The drug development process, from pre-clinical testing through phase III clinical trials, can take anywhere from nine to 12 years, with phase II and III clinical trials consuming half that time. Given those numbers, it is no surprise that pharmaceutical and biotechnology companies are looking for ways to conduct trials more quickly and inexpensively. Enrollment rates in trials are too slow and they seem to be lengthening. Trials are getting bigger and sites are delivering fewer patients. Perhaps no more than 6% of eligible patients actually enter clinical trials. Many clinical trial sites recruit only one or two, or in some cases, no subjects. Over the last several years, Pfizer and other companies have responded by over-recruiting the number of sites they think are needed to make up for sites that will not deliver patients. But that increases per-patient costs, and also makes trial logistics much more complicated. With site-qualification visits and confidentiality agreements, and contracts and budgets, and regulatory documents and investigator meetings, and drug supply and monitoring the sites, as well as data cleaning and other things, the more sites involved the more complicated that becomes. With many studies continuing to demand ever-larger numbers of patients, the cost of running trials has swollen to nearly 30% of companies' drug development budgets. Any delays on the path to regulatory approval and launch can only add to this burden, yet 75% of clinical studies still do not stick to their timetable. These logistical problems, along with financial pressures, have spurred companies to a strategy to reduce the number of countries in which they conduct trials as an imperative to increase study execution speed and reduce costs while maintaining quality.

Metrics used by Pfizer to select core countries for clinical trials

Key clinical trial metrics that have been used by Pfizer to decide on which countries to place studies have included the following:

Start up speed – median number of days from receipt of protocol package to letter of regulatory approval or ethics approval.
Cycle time – median number of days from regulatory approval to last subject first visit
Recruitment reliability – number of actual subjects randomised as percentage of number planned per study.
Why Ireland is not a core country for Pfizer studies

Analysis of this performance data, with consideration of cost and risk factors, has led Pfizer to a new core county foot print of 34 countries representing an approximately 50% reduction in countries previously used in clinical trials. Unfortunately Ireland was not deemed core as it fell short in terms of performance around these key metrics. Why is this? Some thoughts as to key contributory factors:

Fragmentation - research infrastructures are not connected and hard to find. The key opinion leaders and researchers are there and are performing at individual level with individual companies. This activity is not collated, communicated and connected to showcase Ireland’s capacity as a country level
People - Ireland is “person dependent” – you need to know individuals in order to get connected to the right chain of knowledge – it is not a “system”. As described above industry has been evaluating cost cutting and productivity enhancement for several years – this means decisions to involve countries are no longer made on the basis of “who the medical director knew”. It is now in the hands of procurement departments, operational departments whose bonuses are based on performance of countries chosen. Ireland has not evolved from the person based influencing strategy
Performance - not predictable – research approval processes – especially ethics, protracted negotiation process for trial cost negotiation as each facility has different costs for the same service, access to patient populations is quite diffused with lack of connectivity between the various points of care e.g. hospital, GP interface
Cost of patients – the cost of the number of patients Ireland can contribute is too high to justify the effort. Coupled with the fact that Ireland has a limited patient population and also a limited market for the sale of products – the cumulative effect of the investment risk is not a positive one
Compliance - For a number of companies there have been more findings (and of a more serious nature) in regulatory inspections in Irish sites compared to sites in the UK which colours views when it comes to allocating clinical research between sites in the UK and Ireland
Personnel – the recent hiring freeze on research nurses has impacted on Pharma and the perception of recruitment difficulties is very hard to shake
PR - Communication strategy for what Ireland has to offer is fragmented and does not have a strategic lead. Ireland is NOT the right country for EVERYTHING and an uncoordinated communication plan just adds to the perception of confusing, complicated and not joined up national thinking.

What makes a country competitive in clinical research?

Clinical Trial Research is not a commodity, but a sophisticated element of technology in a very competitive environment. Countries wishing to attract high-level clinical research must offer:

Sophisticated healthcare environment
Professional investigational environment - doctors need explicit incentives to conduct research (i.e. "good investigators are good doctors”)
Institutions should have explicit objectives to engage in clinical research; they often charge overheads, so this is a revenue stream, but may be poorly organized
Countries need to offer access to modern diagnostics and treatments, so that data generated will have relevance in a rapidly developing healthcare environment
Comprehensive, integrated information systems are very valuable – they enable effective review/follow up of patients on new treatments with critical evaluation of new treatments.

So where does Ireland go?

The development of a functioning clinical research system is fundamental to the evolution of life sciences in Ireland. Healthcare practitioners play a vital role in identifying unmet medical needs and giving direction and support to life sciences research. The Strategy for Science, Technology & Innovation, 2006 – 2013 (SSTI), highlighted the relatively low levels of translational and/or clinical research underway in Ireland and stated that “the introduction of an R&D culture within mainstream health service has been relatively slow (and) there is a need to strengthen considerably the health services research and policy research capacity nationally”. The reality today is that the resource pressures faced by the hospital system means that research has tended to take ‘second place.’ If Ireland is to become a core site for clinical trials everyone must be committed to making Ireland a beacon for clinical research and we are currently far from that. A shared vision would help us focus on what each part of the chain needs to deliver whilst maintaining their independence. All parts of the chain must be working in the same direction - hospitals, universities, ethics committees and the IMB.

Appointment of Dr Marina Zvartau-Hind as a Director of MMI

Dr Damian O’ Connell, Chair of Molecular Medicine Ireland, is delighted to announce the appointment of Marina Zvartau-Hind, MD, PhD, BC ABPN to the Board of Directors. She replaces Dr Jackie Hunter, Senior Vice-President of GlaxoSmithKline, who recently stepped down after serving more than 2 years on the Board. “We welcome GSK’s continued commitment to the mission of Molecular Medicine Ireland which is to build a sustainable national system to coordinate, support and promote translational and clinical research”, Dr O’ Connell said.

Dr Zvartau-Hind is the Director of GSK’s Neurosciences Medicines Development Centre and Clinical Leader of their Alzheimer disease projects. She is a neurologist by profession who specialises in neuroimmunology.

In 2002, Dr Zvartau-Hind was appointed Head of the Neurodegeneration Group at GSK, providing clinical leadership to multiple studies conducted in areas such as Multiple Sclerosis, Alzheimer disease, stroke, pain and translational medicine. Previously, she gained extensive experience as a clinical investigator on a number of clinical trials including Multiple Sclerosis, Devic’s disease, transverse myelitis, cognition and fatigue.

Dr Zvartau-Hind held the prestigious title of Sylvia Lawry Physician of the Multiple Sclerosis Society from 2001 to 2002 and is a member of both the Scientific Panel of Les Entreprises du Médicament (LEEM) Recherché/Inserm in France with involvement in translational research into Alzheimer disease, and of the International Alzheimer’s Disease Task Force. Furthermore, she is a reviewer for the Neurodegeneration Development Programmes of the Medical Research Council in the UK and is author of a variety of publications in the field of neurosciences.

MMI Technology Platform Web-Portal is now live

MMI is delighted to announce that the Technology Platform Web-Portal is now live. The Web-Portal has been developed, with the input of the research community, to promote and showcase the breadth of Technology Platforms and associated expertise that support clinical and translational research in molecular medicine in our partner institutions and collaborators. The Web-Portal also provides details on how these Technology Platforms can be accessed.

MMI’s Translational Research Strategy for 2009, identified the creation of a Web-Portal as an important contribution to mapping the state-of-the-art technologies and expertise that have been funded to support and advance biomedical research in Ireland. The MMI Technology Web-Portal includes Technology Platforms in molecular medicine for proteomics, genomics/transcriptomics, medical and pre-clinical imaging, mass spectrometry, flow cytometry, data management and IT support to name a few.

Dr Damian O’Connell, Chair of the Board of Molecular Medicine Ireland commented that ‘this Technology Platform Web-Portal makes it easy for all those interested in biomedical research, whether in academia or in industry, to find out what technologies are available to advance their research and how to access them’. He thanked all those who contributed to the development of the Web-Portal.

Dr Jan Guerin, who led the development of the Web-Portal, said that ‘the list of Technology Platforms currently uploaded onto the Web-Portal is by no means complete but is an important first step. We view this as a work in progress and are keen to learn of additional Technology Platforms and to upload these onto the Web-Portal in order to provide as complete a list as possible’.

The MMI Technology Platforms Web-Portal has also been designed to promote ‘news items’ and ‘events’ related to Technology Platforms. News items and/or events for inclusion on the Web-portal should be submitted to tp@molecularmedicineireland.ie

MMI will continue to work with our partner institutions and the funding agencies to ensure that the Technology Platform Web-Portal provides a comprehensive overview of the enabling technologies and associated expertise that is available to support clinical and translational research in Ireland.

To view the MMI Technology Platform Web-Portal, please click on the following link;
www.molecularmedicineireland.ie/tp_web_portal

If you have a Technology Platform that is not currently on the Web-Portal, please click on the link on the home page of Web-Portal which will allow you to upload your information electronically.

MMI welcomes your feedback on this important initiative and hopes that it will prove a useful information resource for the research community, industry, development agencies and funding bodies.

Molecular Medicine Ireland - Review of 2009 and Forward Look

By any standards, the year 2009 was a challenging one. The severity of the economic downturn and the crisis in the public finances reduced funding for research, for MMI’s academic partners and for health care.

MMI’s Unique Selling Point

MMI responded to this challenge by defining MMI’s strategy. The distillation of the input of many stakeholders and the stimulation of the recession, have resulted in greater coherence about MMI’s ‘unique selling point’. As a result of that process, it is much more obvious that the key challenge facing MMI is to use the strengths and resources of our five partner institutions and their associated hospitals to build that national system for clinical and translational research that everyone agrees is needed. While there is a mountain to climb and funding is required, the MMI Directors and staff are clearer today that building a national system for clinical and translational research is something unique that MMI can contribute to the national agenda for innovation and the smart economy. What did MMI and its partners do in 2009 to build the national system for clinical and translational research?

Dublin Centre for Clinical Research

It is particularly good news that the Wellcome Trust/HRB funded Dublin Centre for Clinical Research (DCCR) is open for business! The DCCR is a key part of the infrastructure for clinical and translational research, linking the clinical research centres associated with UCD (St Vincent’s /Mater), the RCSI CRC in Beaumont Hospital and a new CRC being built by TCD at St James’s Hospital. Four studies are underway across the network; five disease groups have been established or recognised and are conducting and/or planning studies to be conducted through the network. Work on an information system for the network is at an advanced stage. The agreement for the new CRC at St James’s has been signed by TCD, St James’s and Wellcome and the tender for the new CRC went to the selected bidders in December, with tenders to be submitted by end January 2010.

Building National Capacity for Clinical Research

The Irish Clinical Research Infrastructure Network (ICRIN) is putting the structures and processes in place to facilitate the conduct of investigator-led studies in multiple sites across the country and across a range of diseases. ICRIN is funded by the HRB and the HSE and operates as a business unit of MMI. The ICRIN Situation Analysis was published and the Clinical Research Roadmap was circulated for comment to key stakeholders. As a result of this initiative, the Department of Health and Children has invited MMI to publish the Roadmap as a contribution to the implementation of the Government’s Health Research Action Plan and to be a partner in building national clinical research capacity. A single application form for ethical approval of clinical studies, other than of medicinal products, has been agreed and is being piloted by five research ethics committees. As a result of a joint workshop with the State Claims Agency on indemnity of clinical research in April, MMI clarified for the research community many of the issues associated with indemnity and the role of the clinical indemnity scheme.

MMI secured funding from Enterprise Ireland to offer a service to SMEs, indigenous companies and start ups in biotechnology to assist them navigate access to the clinical expertise needed to bring their products to market. Thanks to this initiative, a number of firms have either begun or moved closer to clinical trials. As the year ended, ICRIN was making its expertise in clinical trial organisation, research readiness and sponsorship available to the clinical research community to build capacity and to move to a standardised and harmonised approach to research. ICRIN was actively involved during the year with our European colleagues in building the preparatory phase of the European Clinical Research Infrastructure (ECRIN) and benefiting from their approach to supporting multi-centre clinical studies across Europe.

Training in Clinical and Translational Research

Good work was also done in building the human capital for clinical and translational research. A major gap in GCP training has been filled and over 80 people were trained through the courses offered by ICRIN. MMI coordinated a very successful week long programme and organised the annual scientific meeting for the 22 MMI clinician scientist fellows (CSF) in July in NUI Galway. We commissioned an external review of the CSF programme which was very complementary of what has been achieved and provided useful recommendations for maximising the impact of the programme. The shared curriculum for the CSF programme is currently being mainstreamed as a programme to be available to all medical graduates undertaking PhDs in clinical and translational research. MMI staff worked closely with Professor Larry Egan to prepare a PRTLI 5 proposal for a Clinical and Translational Scholars Programme and a decision is awaited at the time of writing. MMI ran five courses on topics relevant to molecular medicine and translational research, including two new courses, on biostatistics and medical imaging for research. Feedback from all courses has been positive.

Supporting Translational Research in Molecular Medicine

Biobanking
MMI had a strong focus on biobanking in 2009. The design phase for GeneLibrary Ireland, an all-island control biobank, was completed and submitted to the funders – the HRB and the Northern Ireland R&D Office (For a copy of this report please go to: http://www.molecularmedicineireland.ie/page/g/t/4).Unfortunately, the funding agencies did not have the funding to move to the next phase. Responding to the need for a more strategic approach to biobanking, MMI has developed Guidelines for Standardised Biobanking to standardise the collection, processing and storage of biological specimens. The use of harmonised procedures will help to provide the proper safeguards and assurances required for sample quality, consistency and integrity among bio-collections at different sites. MMI is pleased to note that these guidelines have attracted great interest in Europe and are likely to be adopted by the emerging European biobanking infrastructure – BBMRI. MMI has also agreed a position paper on a strategic approach to the development of biobanking on the island of Ireland.

MMI Technology Platform Web-Portal

MMI has developed a Technology Platform Web-Portal with the input of the research community, to promote and showcase the breadth of Technology Platforms and associated expertise that support clinical and translational research in molecular medicine in our partner institutions and collaborators. The Web-Portal also provides details on how these Technology Platforms can be accessed. The MMI Technology Platform Web-Portal can be viewed at the following link: www.molecularmedicineireland.ie/tp_web_portal

Communications and Corporate Governance

MMI also improved its communications. The MMI electronic newsletter was an important initiative in bringing MMI’s messages to a wider audience and four issues were circulated in 2009. The website has been developed in a way that will support the wider engagement of the research community. MMI’s Annual Report 2008 was particularly informative and readable. For a copy of this report please go to: http://www.molecularmedicineireland.ie/page/g/s/81. From the point of view of corporate governance, MMI also had a good year. MMI lived within its budget, agreed a budget for 2009/10 and secured a ‘clean’ audit. All reports to funders were completed to a high standard.

Forward Look - What does 2010 hold?

So MMI faces a new year and the new decade in good shape. As mentioned above, MMI’s unique selling point is its potential to mobilise the strengths of the partner institutions and its associated hospitals, to build a national system for clinical and translational research. This national system is necessary to translate research in molecular medicine into innovative diagnostics, therapies and devices that will improve the health of the population and contribute to economic development. A national system for clinical and translational research can become a virtuous circle for innovation. The good news is that same system can serve the needs of academic researchers, industry-led research and those SMEs and start-ups that need access to clinical resources to bring their prototypes to market.

Over the next few years, MMI’s greatest contribution to the national agenda on innovation will be to integrate the capacity and expertise of the partner institutions and associated hospitals to complete this national system and make it accessible to all who need access to clinical resources. The Government’s Health Research Action Plan and the HRB’s Corporate Strategy emphasise the importance of building national capacity in clinical research, both to improve the health of the nation and to add value to the economy. MMI is committed to playing its part in this major national endeavour and all its activities in 2010 are directed to this end.

Damian O’Connell MD BSc PhD
Chair, Molecular Medicine Ireland

MMI welcomes Government's Plan for Health Research

Dr Damian O’Connell, Chair of Molecular Medicine Ireland has welcomed the publication by Mary Harney TD, Minister for Health and Children of the Government’s Health Research Action Plan. ‘The Health Research Action Plan recognises the contribution of research to better outcomes for patients and to creating the ‘Smart Economy’. It is most encouraging that the key Government agencies have signed up to play their part in strengthening our system of health research’, Dr O’Connell said.

In welcoming the Health Research Action Plan, MMI is mindful of the contribution that researchers in Ireland have already made to the global challenge of overcoming disease and protecting health and the added value that their research has brought to the Irish economy. The choreography between government agencies promised in the Health Research Action Plan will enhance the infrastructure and environment for clinical and translational research in Ireland and enable a greater impact on health and wealth

MMI has also welcomed the launch by Minister Harney of the Health Research Board’s Strategic Business Plan 2009-11. Dr Ruth Barrington, CEO of MMI said that it is encouraging to see the commitment of the HRB to driving the development of excellent clinical research, including applied biomedical research, within a coherent health research system.

‘MMI’s mission is to mobilise the strengths of our partner institutions to build a sustainable national system for translational and clinical research. We look forward to working with the HRB to realise our shared goals for clinical research’, Dr Barrington said. MMI is finalising the Clinical Research Roadmap, prepared by experts in every aspect of clinical research brought together through ICRIN – the Irish Clinical Research Infrastructure Network. The Roadmap will be an important contribution from the clinical research community to building a national system for clinical research.

The Health Research Action Plan, prepared by the Health Research Action Group chaired by Mr Jim Breslin, Assistant Secretary, Department of Health and Children, assigns responsibility for key actions in constructing a national health research system. Key responsibilities assigned include:
• Direct and lead the national health research system – Department of Health and Children
• Develop a research governance framework for research in the health services – Health Service Executive
• Streamline and consolidate ethical approval structures – Department of Health and Children
• Develop strategic research clusters of academics, clinicians and industry investigators in experimental and translational medicine - Science Foundation Ireland

The Health Research Action Plan is available at: http://www.dohc.ie/publications/health_research_action_plan.html
The HRB’s Strategic Business Plan is available at: http://www.hrb.ie/uploads/tx_hrbpublications/HRB_Strategy_2010-2014.pdf
A press release issued by the Department of Health and Children is available at: http://www.dohc.ie/press/releases/2009/20091104.html

Record attendance at MMI Techniques & Strategies in Molecular Medicine course

The seventh annual running of the MMI course ‘Techniques & Strategies in Molecular Medicine’ took place in the UCD Conway Institute on 8-9 December 2009. The 114 attendees from MMI partner institutions heard lectures from a total of 17 speakers from UCD, RSCI, TCD and NUI Galway over the two days. In addition to MMI partner institutions, attendees travelled from DCU, QUB, DIT, NUIM and UL.

The course is designed to give bioscientists and clinicians a broad overview of research techniques and their application and to give graduate students a basic knowledge of technologies outside their own project or lab that may be of current or future use.


	Dr Leonie Young (RCSI) during her talk on Immunodetection methods on cell and tissue extracts

The first day of the course covered techniques for analysis and manipulation of genes including RNA detection and quantitation, gene expression, RNA interference, polymorphism, transgenics and knockouts, and cloning strategies. A lecture on model organisms was also presented and a lecture on protein-protein interactions, the first of a series of protein techniques lectures.


A talk on Protein expression and purification was given by Dr Henry Windle (TCD)

The protein theme was continued on the second morning with lectures on protein expression, protein-protein interactions, biomedical applications of expression proteomics and an introduction to the technique of mass spectrometry. Cells & Tissues lectures featured flow cytometry, immunodetection methods, laser capture microdissection, stem cells, and high content screening and analysis platform technologies. A lecture on Imaging using Fluorescent/Confocal Microscopy was also added to the programme for the first time this year.


	At the wine reception: Dr Mark Watson (MMI), Prof Pierre De Meyts (Hagedorn Research Institute), Prof Boris Kholodenko (Systems Biology Ireland), Prof Walter Kolch (Systems Biology Ireland)

The course finished with a keynote lecture from Professor Pierre de Meyts, Hagedorn Research Institute, Denmark. Professor de Meyts gave the audience an account of his cutting-edge research with a lecture entitled ’Structure-based systems biology of insulin and IGF-I receptors signalling’. The keynote lecture and the wine reception which followed were sponsored by novo nordisk. The course also benefited from sponsorship from Applied Biosystems.

The course programme and lecture abstracts, and the list of course contributors are available here.

ICRIN pilots Research Readiness Programme

In January 2010, ICRIN began piloting a Research Readiness Programme with a selected number of research institutions, clinical research centres and their associated researcher teams in Ireland.

One of the catalysts for this exercise is a request from the European Clinical Research Infrastructure Network (ECRIN) to showcase Irish research capabilities on a web portal with the aim of promoting access and linkages between the research groups and clinical research centres (CRCs) and clinical trial units (CTUs) at European level.

The overall goals of the Research Readiness Programme are to evaluate the research systems which are already functioning well at a more granular level, identify the areas where more consistency of approach will be of benefit (sharing best practice) and gain information from the research teams on the research infrastructure elements which would be best addressed at a national level.

An additional goal of the review is the development of a report to inform the funders and agencies of the research infrastructure options which would best support Irish research. This report would address questions such as what skills and expertise might be systematically developed and supported locally in decentralised hubs and what infrastructural elements might be best contained in a national coordinating body. The research systems being evaluated are depicted in the diagram below:

The Research Readiness process is initiated on foot of the scoping visit and comprises four main parts:

Identification of a proportion of research protocols carried out by respective institutional research teams as vehicles to assess the systems noted in the diagram above
Completion of a report for each institution with recommendations to be delivered in the form of a face to face discussion and review
Development of a specific implementation plan for agreed recommendations
Review and feedback plan for any new processes and solutions deployed to ensure they are validated and are effective.

MMI Guidelines for Standardised Biobanking - Consultation Phase

As a contribution towards a more strategic national approach to biobanking, and building on the work undertaken in the Design Phase of GeneLibrary Ireland (funded by HRB and the R&D Office), MMI has developed guidelines to standardise the collection, processing and storage of biological materials donated for use in research. The aim of the Guidelines is to ensure sample quality, consistency and integrity of bio-collections at different clinical and research centres in Ireland. The use of standardised protocols for sample collection, processing and storage will help to ensure consistency and harmonisation across the different sites. These Guidelines have been drafted with reference to international best practice in biobanking.

The Guidelines have been approved by the Board of MMI. Prior to issuing them in final format, MMI would welcome the input of the stakeholders in health research with an interest in biobanking on the draft Guidelines and to their potential contribution to developing a more strategic approach to biobanking in Ireland. To this end MMI is conducting a consultation phase to invite comments on the draft Guidelines prior to publication

The consultation phase will close on Friday February 12th 2010. To get a copy of draft Guidelines please email research@molecularmedicineireland.ie.

MMI welcomes the views and comes from those engaged in biobanking within the timeline provided above.

Pilot Common Ethics Form now available

MMI has been supporting the development of a Common Ethics form for clinical research studies not covered by SI 190. Over the last six months a group of hospital Research Ethics Committees administrators have been meeting to develop the common form.

A pilot version of the form is available on the MMI web site and is currently being piloted by Research Ethics Committees associated with the Dublin Teaching Hospitals, HSE North East, HSE South East and the Irish College of General Practitioners. The pilot phase will take until May 2010 and the form will then be finalised and made available for general use by Research Ethics Committees across Ireland.

"A common form will offer a range of advantages to applicants and Research Ethic Committee members", says Jeremy Towns of the DCCR who Chaired the Group.

He added, "Educational programming can be developed to train researchers and research nurses on how the form should be completed and it saves time for those researchers wishing to conduct multisite clinical research. The form also incorporates smart form technology, which provides guidance to applicants as they complete the form."

To view the current version of the form please go to: http://www.molecularmedicineireland.ie/page/g/s/82

The Committee would welcome feedback on the form. This can be sent to jeremy.towns@molecularmedicineireland.ie

Molecules to Medicines course and workshop gives insight into biopharmaceutical industry

The fourth running of the MMI Molecules to Medicines course and workshop took place on 5-6 November 2009 at St James’s Hospital, with 27 attendees.

On Day 1, staff from Pfizer Grange Castle presented on discovery, development and manufacturing of biopharmaceuticals, with a clinical perspective provided by Professor Joe Keane (St. James’s Hospital & Institute of Molecular Medicine, TCD), whose lecture was entitled "Developing drugs – anticipating toxicity – and doing something about it".

The discovery lectures, given by Dr Jonny Finlay (Global Biologic Therapeutics, Pfizer), introduced the business of discovering biopharmaceuticals and discussed current biopharmaceutical product candidates and next generation technologies. Dr Patrick Gammell (Scientist, Pfizer Grange Castle) covered the next stage of the biopharma process in the development section of the programme, with lectures on cell line and process development. This was followed by lectures on manufacturing given by Dr Paul Dillon (Senior Scientist, Pfizer Grange Castle), introducing the science and technology of biopharmaceutical manufacturing and the application of molecular technologies in manufacturing environments.

A workshop was held on 6 November for a select group of course attendees. Here the three Pfizer speakers from the course led study groups involving discussion of key issues arising during biopharmaceutical discovery, development and manufacturing. Workshop participants broke up into small groups to discuss solutions to specifically designed problem sets. Feedback from this practical workshop was extremely positive.

As a follow-on from the Molecules to Medicines course, a trip to the Pfizer Grange Castle Wyeth campus will be organised for a limited group of course attendees on 7 December 2009. The tour will be hosted by Dr Patrick Gammell and will include a facility video presentation, a facility tour and a round-table discussion.

MMI Clinician Scientist Fellow involved in ground-breaking breast cancer research

Ground breaking research from the Breast Cancer Research Group in NUI Galway, demonstrating that microRNAs are measurable in the blood of breast cancer patients and suggesting that a particular microRNA can be used as a breast cancer specific tumour marker, was well received at the recent annual San Antonio Breast Cancer Symposium, and was reported on the front page of the Irish Times (see http://www.irishtimes.com/newspaper/health/2009/1222/1224261097798.html). The work was led by Professor Michael Kerin, presented by Dr Helen Heneghan and co-authored by Dr Nicola Miller and Dr John Newell. Research by MMI Clinician Scientist Fellow Dr Aoife Lowery formed much of the background to this study. Dr Miller describes the research below.

MicroRNAs and cancer
The incidence of breast cancer is increasing worldwide. In the context of increasing disease burden, translational research is of vital importance to clinical advancement. The evolution of high throughput technologies, such as microarray gene expression profiling, have facilitated breakthroughs that have altered traditional thinking regarding breast cancer as a disease entity. The discovery of mi(cro)RNAs as regulators of gene expression represents a paradigm changing event in biology and medicine. It is now recognised that miRNAs are profoundly important in carcinogenesis through their regulation of oncogenes and tumour suppressor genes. This knowledge, coupled with the fact that miRNA expression profiles have shown superior accuracy to messenger RNA at classification of human cancer according to developmental lineage and differentiation status, indicates that understanding miRNA biology will be integral to an improved understanding of breast cancer biology. It is likely that uncovering the miRNA layer of genetic regulation will be a crucial step in the development of accurate prognostication and targeted therapy in breast and other cancers.

Developing microRNA expression signatures to classify breast tumours
In order to comprehensively analyse miRNA expression in breast tumours, global miRNA profiling was undertaken in early stage matched breast tumour specimens in collaboration with Dr. Vladimir Beněs at EMBL, Heidelberg. Analysis of microarray expression data was performed in collaboration with Dr. Graham Ball at Nottingham Trent University. Artificial Neural Networks (ANN) were chosen as the bioinformatics tool due to their ability to cope with complex data, their potential for modelling data of high nonlinearity and their ability to identify patterns within a dataset that can discriminate between subgroups.

Using this approach miRNA signatures predictive of ER, PR and HER2/neu receptor status were generated, which was the first report of ANN analysis of miRNA expression data (Lowery et al, 2009). These clinical parameters were chosen as they remain the current prognostic markers used in breast cancer; clinical decisions regarding adjuvant therapy and the clinically relevant breast cancer sub-groupings are based broadly on ER, PR and HER2/neu receptor status. Our results highlight the potential for developing miRNA expression signatures as diagnostic and prognostic tools for breast cancer. The capacity of miRNA expression profiles to classify breast tumours according to the clinicopathological variables currently used to predict disease progression, indicates that these signatures may contribute to improved prognostication and selection of patients for adjuvant therapy, as has shown promise with mRNA signatures.

Assessing the potential for circulating microRNAs as breast cancer biomarkers
Inherent characteristics of miRNAs such as their lower complexity, tissue specific expression profiles and their stability make these molecules ideal candidates as biomarkers reflective of physiological and pathological states. Recent blood-based miRNA profiling studies have generated the concept that circulating miRNAs hold much potential as novel non-invasive biomarkers for cancer and other disease processes. These preliminary reports have suggested the clinical utility of systemic miRNA analysis for several cancers including prostate, colorectal, lung, and lymphomas, as well as in the management of non-malignant diseases such as diabetes mellitus and drug-induced hepatitis. To date there has been no report regarding their usefulness, if any, in breast cancer management. Our aim was to assess the potential for circulating miRNAs as novel minimally invasive breast cancer biomarkers.

Real-time PCR analysis was carried out to determine the quantities of a panel of candidate miRNAs in tissue and blood specimens from patients with breast cancer and in age-matched disease-free control individuals. We found that cancer specific miRNAs were detected and significantly altered in the circulation of breast cancer patients compared to healthy controls. In particular two systemic miRNAs were elevated in breast cancer patients and could discriminate breast cancer cases from controls with high specificity and sensitivity. Furthermore, blood miRNA levels were even elevated in patients with in-situ disease, the earliest form of breast cancer, suggesting a possible role for circulating miRNAs as cancer screening tools (Heneghan et al, 2010).

Additional evidence from our study that supports systemic miRNAs as ideal cancer biomarkers:
1. Tumour and blood miRNA levels reflected tumour burden with higher levels of miRNA found in patients with more advanced stage of disease.
2. Circulating levels of miRNAs decreased in cancer patients post-operatively, to levels comparable with control subjects, following curative tumour resection
3. Specific circulating miRNAs correlated with certain clinicopathological variables, namely nodal status and oestrogen receptor status.

While further prospective evaluation of blood-based miRNAs, in breast and other cancers is needed to validate these findings, our results suggest that there is a very real and imminent potential for circulating miRNAs to fill the void in clinical practice for a sensitive and specific minimally invasive biomarker, to aid in the diagnosis, prognostication and follow-up of breast cancer.
Dr Aoife Lowery holds an MMI Clinician Scientist Fellowship. The MMI Clinician Scientist Fellowship Programme is funded through PRTLI Cycle 4 administered by the Higher Education Authority.

References

1: Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, Benes V, Schmidt S, Blake J, Ball G, Kerin MJ. MicroRNA signatures predict Estrogen receptor, Progesterone receptor and HER2/neu receptor status in Breast Cancer. Breast Cancer Res. May 11(3):R27 2009. [Epub ahead of print] PMID: 19432961

2: Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. March 2010.

Dr Aoife Lowery was awarded the MMI CSFP gold medal following presentation of her work during the 2009 Annual Meeting of the MMI Clinician Scientist Fellowship Programme.

For further details on the MMI CSFP, please click here

MMI Course - Human Disease Genomics: SNPs, GWAS and Next-Gen Sequencing

The analysis of genetic determinants in human disease, particularly in multifactorial conditions such as cardiovascular disease, diabetes and schizophrenia, has advanced considerably in recent years due to the availability of high-density maps of Single Nucleotide Polymorphism (SNP) markers, new insights into human genome structure from the International HapMap Project and novel analytical methods.

This course, running over two days, aims to introduce researchers to key strategic considerations in designing and performing gene-mapping studies.

Date: 22-23 June 2010
Venue: Institute of Molecular Medicine
Trinity Centre for Health Sciences, St James's Hospital

For further information on this MMI course, please see here

Course Sponsors

Major Sponsor:

Irish involvement in BBMRI, one of the ESFRI Biomedical Sciences Infrastructures

The Biobanking and Biomolecular Resources Infrastructure (BBMRI) is one of the recommended ESFRI Biomedical and Life Sciences Infrastructures. The preparatory phase of BBMRI is currently underway and is funded by the European Commission, through Framework Programme 7 (FP7). BBMRI is being funded to establish a pan-European biobanking network through the coordination and harmonisation of the biomolecular resource infrastructure, including population-based cohorts, disease orientated cohorts, twin registries and clinical case/control studies. BBMRI will build on existing sample collections, resources, technologies, and expertise, which will be specifically complemented with innovative components and will be properly embedded into European scientific, ethical, legal and societal frameworks.

BBMRI’s preparatory phase aims to provide the basis for the operational biobanking infrastructure and plans to provide a strategy and structure for:

a pan-European inventory of major European biobanks
complementation of existing resources and technologies
establishment of clear access rules
facilitation of transnational combination and exchange of biological materials and data
ensuring coordinated development of resources and technologies
reducing the fragmentation of the scientific community
developing a sustained financial basis for years to come

For further information on BBMRI please click on the following link; www.bbmri.eu

Ireland is playing a leading role in BBMRI’s Stakeholder Forum, with Michael Griffith as Chair and Derick Mitchell as Executive Manager supported by the Irish Platform for Patient Organisations, Science and Industry (IPPOSI). The Stakeholder Forum is actively collating the input and requirements of its broad stakeholder community comprising patients, clinicians, funding organisations, associated project partners, industry, and users. In addition, the Stakeholder Forum provides an opportunity for patients and users to interact systematically with investigators in biobanking and industry. Further information, including the outcome reports from the BBMRI Stakeholders' Forum events is available on the IPPOSI website at www.ipposi.ie.

Ireland’s participation in BBMRI is coordinated through Molecular Medicine Ireland and the Health Research Board is the sponsoring agency.

BBMRI is putting together an inventory of all biobanks across Europe to identify what biobanks should be part of this pan-European network of biobanks. If you would like your biobank to be part of this inventory BBMRI is requesting that you complete an on-line core questionnaire which is available at www.bbmri.eu/index.php/catalog-of-european-biobanks. BBMRI has advised that completion of the ‘core questionnaire is mandatory for a biobank to be registered with BBMRI’. Currently Ireland has two biobanks registered with BBMRI. MMI will continue to engage actively with the research community in 2010 to increase the number of Irish biobanks registered on BBMRI’s web-based catalogue of European biobanks of high quality in order to reflect the breadth of bio-repositories available in Ireland that supports biomedical research.

Please contact research@molecularmedicineireland.ie if you could like additional information on participation in BBMRI.

News in Brief

High demand for GCP training in 2010

ICRIN are delighted to announce they will be continuing their successful Good Clinical Practice (GCP) training programme this year. Last year we trained a total of 86 people on clinical research and the principles of GCP. We will be holding an additional 7 courses around Ireland in 2010 and will be opening registration… More »

DCCR hosts networking event with Biomedical Diagnostics Institute

On 2nd December, the Dublin Centre for Clinical Research hosted a networking event with the Biomedical Diagnostic Institute (BDI). The DCCR is a clinical research network funded by the Wellcome Trust and HRB. The evening event featured an overview presentation by Professor Dermot Kelleher, Clinical Director and Principal Investigator of the DCCR Programme.

MMI/ICRIN hosts workshop on clinical studies for medical devices

On 29th October, the Irish Clinical Research Infrastructure Network (ICRIN) and Molecular Medicine Ireland (MMI) hosted a very successful workshop for the medical device industry entitled “Impacting healthcare through facilitating clinical studies of medical devices/diagnostics in Ireland”. It was held in the Old… More »

Certificate in Nursing (Clinical Research) 2010/2011

The Faculty of Nursing & Midwifery at the Royal College of Surgeons in Ireland in partnership with the Clinical Research Facilities at Beaumont Hospital (RCSI), the Mater Hospital and St Vincent’s Hospital (UCD), are offering the following 6 month educational programme commencing September 2010:

CERTIFICATE IN NURSING (CLINICAL RESEARCH)
(Minor Award: Level 9)

… More »

Patient leading vision research honoured by Trinity College Dublin

Michael Griffith, founding member and current Chairman of the Irish charity Fighting Blindness was honoured by the Senate of Trinity College, Dublin with the honorary degree of Doctor of Science (Honorius causa) during a conferral ceremony on Friday December 11, 2009.

Long a champion of research into genetic blinding disorders such as the genetically inherited Retinitis… More »

Visit to the TCD 3D Visualisation Suite for MMI Course Attendees

Course Poster Following the fourth running of the MMI Drug Design & Delivery course, which took place on 12-13 October 2009 in RCSI, a small group of attendees will visit the TCD 3D visualisation facility on Wednesday 10 February 2009.

The visit, led by Dr Amir Khan… More »

CSTAR - Centre for support and training in analysis and research

Irish Clinical Research Infrastructure Network (ICRIN) is pleased to announce a working relationship with the Centre for Support & Training in Analysis & Research (CSTAR). CSTAR specialises in the biostatistical and methodological areas of quantitative and qualitative research. It offers a support and advisory service to all health researchers working in biomedical, translational, clinical and… More »

Issue 4 - February 2010

Contents