15 July 2005 print
Task Force Update
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Rare diseases in Europe : tomorrow's vision, a common vision
This year's European Conference on Rare Diseases, held in Luxembourg on 21 and 22 June was, above all, an occasion for reinforcing the importance of partnerships and of sharing experiences at all levels.

Over two days of stimulating presentations, combining personal stories with updates on European initiatives, a wide spectrum of stakeholders answered the key question asked by Terkel Andersen, president of Eurordis, at the beginning of the conference: 'How do we make the most of Europe by combining resources?'.

Fernard Sauer, Director for Public Health at the European Commission, talked of the importance of a global approach to rare diseases in research, information and training, social benefits, hospitalisation and outpatient treatment, and the need for special combined efforts to prevent morbidity, early mortality and the reduction of individuals' quality of life.

Other speakers highlighted many of the existing bottlenecks to progress: lack of epidemiological data, difficulties in coding rare diseases, national legislation, lack of national funding for research, lack of funding continuity, 'postal code lottery' diagnosis... But solutions to these problems were also presented with many local experiences proving that, through partnership, it is possible to improve the quality of life of patients.

Yann Le Cam, Chief Executive of Eurordis, joined many speakers in applauding the success of the EU orphan drugs regulation, this year celebrating its fifth anniversary. But looking beyond this success he highlighted five key tasks for the future :

  • To develop more orphan drugs for unmet medical needs
  • To increase the number of authorised medicines for rare diseases by improving the clinical development success rate
  • To promote patient access to orphan drugs in each member state
  • To settle the debate on orphan drug pricing
  • To adopt a more international approach to designation, protocol assistance, marketing authorisation assessment and availability to patients

  • The take-home messages for professionals in the field, as perceived by Segolene Ayme, leader of the Rare Diseases Task Force, included the following requests:
  • To produce information better adapted to families and to non-specialist social and health workers
  • To offer expert care close to where people live
  • To develop tele-medicine and expert advice from reference centres
  • To lobby at national level for measures that have proved their worth in other countries
  • For DG Research to support rare diseases research in all fields, not just in genomics
  • For DG Sanco to consider supporting networks for the longer-term development of resources for the rare diseases community

  • For those of you who were unable to attend, the presentations from the conference will be accessible on the conference website.

    This month's newsletter highlights many of the initiatives already in place, or being planned, to increase collaboration between countries and between stakeholders in Europe: from European clinical trials networks to the efforts of the primary immunodeficiencies community to bring patients together with doctors and researchers. Europe is moving in the right direction.

    The next rendez-vous for the rare diseases community in Europe will be in London in October when EPPOSI - the European Platform for Patients' Organisations, Science and Industry - organises its annual workshop on Partnering for Rare Disease Therapy Development, this year in collaboration with US colleagues from NORD and NIH. The workshop theme 'People with Rare Diseases - No Longer Alone in the World' reflects the feelings expressed by many present at the Luxembourg event. Rare diseases are firmly on the public agenda and now we must work together - nationally, internationally - to ensure that they stay there.

    Deadline for submissions

    We welcome your contributions to OrphaNews Europe.
    Please send your ideas for articles by contacting the editor here.

    OrphaNews Europe is taking a summer break.
    The next edition will appear in mid-September.
    Deadline for the next issue is
    1 September 2005.


    Task Force Update
    Third meeting of the Rare Diseases Task Force
    The third meeting of the Rare Diseases Task Force was held on 20 June in Luxembourg. Members approved a final version of the Task Force mandate and discussed future plans for the Task Force work programme which will mainly take place through expert working groups.

    Juliette Bloch from the French national institute for health surveillance (INVS) in Paris presented a model for public health indicators for rare diseases which she is setting up in France, in the context of the National Plan for Rare Diseases. The INVS will be collecting epidemiological data on a limited number of rare diseases from national centres of reference, registers, administrative databases, death certificates, hospital records, inscriptions on long-term illness lists and from institutions managing disability allowances. Currently the INVS is using a process of expert consensus to elaborate a list of criteria on which to determine which diseases should be given priority for public health monitoring. This work will feed into a Task Force Working Group on public health indicators which will identify strategies allowing comparisons to be made between health indicators for rare diseases in different European countries. This Working Group, led by Juliette Bloch, will start work in the autumn.

    Ségolène Aymé, the Task Force leader, presented the work plan of a second Task Force Working Group, on coding and classification, which is in the process of being set up. This Working Group will work in close collaboration with the WHO to propose an extension of the ICD-10 classification incorporating rare diseases. The group will identify the rare disease community’s needs in coding and classification and collect existing expert classifications serving a specific purpose but which may have wider applicability. In the early stages of this Working Group there will be close collaboration with the working group on public health indicators.

    Dr Aymé also presented the Working Group on standards of healthcare which met on 3 June in Paris to discuss the concept of European centres of reference for rare diseases. A full report of the meeting is available here, along with presentations given by representatives from Denmark, France, Italy, Spain and the UK. The work of this group is being fed into a High Level Group set up by the Commission to debate the issue of centres of reference more widely and for which rare diseases is being taken as a model. This high level group met on 16 June in Brussels where the Task Force Working Group was officially mandated to continue investigating this theme on behalf of the High Level group.

    The Task Force members also agreed to tackle the subject of genetic testing for rare diseases in Europe in response to a request from DG Research, and data confidentiality, which is relevant to many of the issues already being studied by the Task Force.

    Any readers who feel that they could usefully contribute as experts to any of these Task Force Working Groups should contact the RDTF secretariat.

    A full report of the 3rd Task Force meeting will soon be available on the RDTF website.


    Let us know what you think...
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    Spotlight on...
    Clinical research in rare diseases: big challenges for small numbers
    Translating academic research into safe and effective innovative treatments for patients is a particular challenge where the treatment of rare diseases is concerned. By definition the patients affected are small in number and geographically dispersed and whilst an effort has been made, through the EU orphan drugs regulation, to encourage pharmaceutical companies to develop specific drugs for these disorders, clinicians are still faced with enormous challenges in mounting clinical trials to test their safety and efficacy. As in many other areas of rare disease research one of the solutions lies in networking.

    This spotlight features two recent European initiatives which aim to promote increased networking between stakeholders in the field and an interview with Dr Bruce Morland, a practicing clinician in the UK whose research is centred on clinical trials for rare childhood cancers.

    The OrphanXchange project: strengthening co-operation between Academia and Industry

    Culturally, researchers have little experience of technology transfer and although multiple opportunities exist they generally suffer from a lack of visibility. With this in mind, the European portal of rare diseases and orphan drugs, Orphanet, set up the OrphanXchange project one year ago to highlight opportunities and facilitate collaboration and partnership between academia and industry in the field of rare diseases.

    With support from Orphanplatform, a European Union project (FP6, DG Research, contract LSSM-CT-2004-503246), this dedicated service is a tool to boost the development of diagnostics and therapeutic products. The website www.orphanxchange.org is a market place of innovative research projects and potential orphan designations that are of interest to pharmaceutical and biotech companies. Registered users can search the database for specific projects and directly contact investigators wishing to turn their research into a marketed product.

    Currently, registered users come from 25 different countries (Europe, USA, Japan, Brazil, India…) with half representing the private sector: big Pharma as well as SMEs, biotech, venture capitalists and consultants.

    OrphanXchange is playing a pivotal role in facilitating co-operation between industrial companies and researchers for the rapid setting up of clinical developments.

    European Clinical Research Infrastructures Network (ECRIN)

    Differences in health and legislative systems in Europe have led to a fragmented clinical research effort which reduces the capacity to enrol patients in clinical studies, increases the costs of clinical research, and hampers scientific productivity. For academic infrastructures of clinical research and investigators doing multinational studies in Europe, fragmentation raises obstacles - such as informed consent, ethical review, data monitoring, adverse events, insurance - creating bottlenecks along the way.

    The ECRIN project launched in 2004 and funded through the EC’s Sixth Framework Programme (contract LSHM-CT-2004-511963), was designed to bridge such fragmented organisation and to improve the quality and efficiency of clinical research in Europe. The project aims to provide an infrastructure allowing for bottom-up harmonisation of support, training, and practice of clinical research in Europe, based on the interconnection of national networks of clinical research centres and trial units. A major objective of ECRIN consists of stimulating and facilitating the creation of new centres and national networks, especially in the new member states, for their subsequent connection to the European network and building the necessary critical mass at the European level.

    ECRIN also plans to provide support for public sponsors of clinical trials whose role as a single sponsor in multinational studies is made increasingly complex through the implementation of the EU Directive 2001/20/EC on clinical trials. This support is particularly important in the field of rare diseases and orphan drugs where transnational co-operation is essential and where trials are often beyond the scope of industry investment.

    ECRIN currently covers six European countries (Denmark, France, Germany, Italy, Spain, Sweden) and Canada, in association with the European Forum for Good Clinical Practice, with plans to extend to other EU member states.

    ...with Dr Bruce Morland, Birmingham Children's Hospital
    Dr Bruce Morland is a paediatric oncologist and Clinical Director at Birmingham Children's Hospital in the UK. His major research interest is the development of Phase I and II clinical trials for new drugs in the treatment of childhood cancer. He chairs the New Agents Group of the United Kingdom Children's Cancer Study Group (UKCCSG) and the clinical trials committee of the European consortium for drug discovery, Innovative Therapies for Childhood Cancer (ITCC). Dr Morland is also an academic representative on the EMEA's Committee for Orphan Medicinal Products Working Group of Interested Parties.

    OrphaNews Europe asked Dr Morland about the challenges that academics face when setting up clinical trials for rare diseases:

    What are the main problems encountered by clinicians wishing to conduct clinical trials in rare diseases?

    BM - By definition because of the rarity of these conditions it is essential to build up networks of clinicians in order to have sufficiently large numbers of patients to conduct trials. Clinical trials need numbers. To date we've not been very good at looking at new methodologies for conducting trials with small numbers and this needs to change. Many of us though have a traditional grounding in large trials and lack the knowledge to undertake small trials. There also needs to be a wider recognition within peer groups and regulatory bodies that small trials in rare diseases can be powerful and informative. The world of academia is competitive e.g. the push to publish first on a topic. This "culture" is somewhat counterintuitive when it comes to collaborative links necessary to run trials. We struggle to organise collaborative clinical trials in major disease groups e.g. adult cancer, where numbers are never an issue, why is this?

    Are academics reticent to develop collaborations with industry in this field?

    BM - Absolutely not! It is impossible for academic groups to develop drugs for humans without the input from industry. The regulations around medicinal product manufacture means it's a very expensive process which academic groups simply can not afford. Long gone are the days when you could squirt something into patients you cooked up in your lab earlier that day! (Thank goodness!). However are industry really interested in rare diseases? Many would say no, they're after big bucks, and whilst orphan designation addresses this to some degree it's interesting big Pharma companies haven't engaged with rare diseases to a great extent....why? Putting industry in contact with the right clinical research teams and visa versa is not easy. It usually relies on ad hoc individual person-person contact and is too unstructured to be efficient. Networks clearly help but even where they exist linking to industry is haphazard.

    Full interview with Dr Bruce Morland

    Joint position on the disclosure of clinical trial information via clinical trial registries and databases

    EU clinical trials directive 2001/20/EC


    EU Policy News
    New EU health data published
    The first set of EU-wide health data from the European Community Health Indicators (ECHI) project has been published on the Commission's Public Health website. The aim of ECHI is to produce better and more comparable data that will enable policy makers to track developments in the health status of EU populations. The ECHI indicators aim to cover the 25 MS, the EU Candidate Countries (Romania, Bulgaria, Turkey), the West Balkan Countries, the USA, Canada and Japan and the data they contain is available in English, French, German and Spanish. The ECHI pages on the Public Health website will be developed over the coming months and updated on a regular basis .
    DG Research
    Researchers' wish-list for rare disease research in Europe
    Representatives of the European rare diseases research community made the most of an opportunity offered by a workshop organised by the European Commission’s DG Research Health Directorate in April to formulate their wishes for future funding in the field.

    Participants included coordinators and participants in projects of Fifth and Sixth Framework Programmes for Research, patients’ representatives, biopharmaceutical industry representatives, the European Medicines Agency (EMEA), and the European Commission.

    The aim of the workshop was to provide the European Commission with specific recommendations and other suggestions for optimising Rare Disease research in the EU programmes.

    Two days of presentations and fruitful discussion led participants to come up with a list of recommendations relating to the size and type of projects, infrastructure needs and scientific priorities.

    Given the importance of rare diseases as models for more common disorders, and the high burden they represent for society, the participants also recommended that research on rare diseases be given a separate bullet point within the Health theme of the Seventh Framework Programme for research (FP7) which will run from 2007-2013.

    At the European Conference on Rare Diseases held in Luxembourg last month, where these recommendations were made public, the European Commission representative from DG Research, Alan Vanvossel, confirmed that the Commission aims to implement the priorities identified by the workshop participants to the extent possible in the next Framework Programme, taking the EU financial possibilities into consideration.

    The research community will therefore have to wait to see whether this wish-list translates into more euros for rare diseases in FP7. The next step will depend on budgetary negotiations which cannot go forward until Member States agree on an overall budget for the EU.

    Speaking at the Luxembourg conference, Ketty Schwartz of the Institut de Myologie in Paris and co-chair of the April workshop, warmly encouraged stakeholders in the field to lobby their governments and the European Parliament in the meantime to ensure that rare diseases remain high on the European research agenda.

    Simplifying the Seventh Framework Programme
    Any of you that have participated in EU research framework programme applications may well have been frustrated by the complexity of the process. DG Research commissioner, Janez Potočnik, aware of these frustrations, has made a commitment to simplifying all levels of EU research support and is using the opportunity and challenge of the Seventh Framework Programme (FP7) to further simplify and rationalise the process.

    In this context the European Commission is offering all researchers the opportunity to offer their views on the ten proposed measures for simplification contained in the staff working document on simplification that accompanied the Commission proposal on FP7. Comments from all participants concerning other issues that would be addressed by the Rules for Participation such as intellectual property provisions, evaluation criteria, financial collective responsibility and other participation principles are also welcome.

    The closing date for comments is 31 August 2005.

    New procedure for EU pharmaceutical guidelines
    Following a consultation exercise on transparency, the European Medicines Agency has finalised a new procedure aimed at putting in place a transparent process for the development, consultation, finalisation and implementation of pharmaceutical guidelines.

    Pharmaceutical guidelines are a key part of the Agency’s work within the European Union pharmaceutical regulatory system and provide essential information to be taken into account in the research and development of new medicines.

    The new procedure will come into effect for all draft and final guidelines published by the EMEA after 1 September 2005.


    National & International Policy Developments
    Policy developments in EU member states
    Franco-German collaboration on rare disease research planned
    At a workshop in Potsdam, Germany on 6 - 7 July, representatives of the French and German academic community and research ministries met together to discuss how the two countries could collaborate on joint research projects in rare diseases. Both countries have national funding initiatives for rare disease research and are keen to propose a common call for proposals.

    Participants discussed which common problems in rare disease research could be adressed by a joint call and whether there should be a thematic focus. Whilst it is not envisaged to select specific disease groups for the call, the possibility of focussing on specific types of investigations was discussed.

    In addition, participants also discussed the most realistic structure for the projects to be funded (minimal number of partners, amount of funding, duration of projects) and whether there is a need for easier access to, and better coordination of research infrastructures for rare diseases.

    A full report of the meeting and details of the joint call will be published in a future edition of the newsletter.

    UK: Nowgen - bringing genetics research to the community
    Launched in January 2005, Nowgen, the North West Genetics Knowledge Park based in Manchester, is one of six similar Parks in the UK funded by the Departments of Health and of Trade and Industry to ensure that the outcomes of human genetics research are successfully applied. Nowgen has an active programme of work in health services and new genetics research, bioethics and public engagement, and provides education in genetics to the health professional and business sectors.

    A partnership between Central Manchester & Manchester Children's University Hospitals NHS Trust, Lancaster University and the Universities of Liverpool and Manchester, Nowgen is led by Executive Director, Dian Donnai, professor of medical genetics at the University of Manchester and Dr Helen Middleton-Price, as Director. A further 22 staff are housed within the purpose-built centre.

    Nowgen is also actively involved at the European level through a European projects office and is currently a partner in three European networks: the European Skeletal Dysplasia Network (ESDN), a research and diagnostic network; Orphanet/Orphan Platform, a European database of rare diseases; and Eurogentest, a network to structure, harmonise and improve the overall quality of genetic services across Europe.

    Last month, Nowgen announced the start of a new service - the Nowgen Network - to support collaboration and information sharing between public bodies, voluntary groups and commercial organisations working in the diverse field of genetics. The Nowgen Network uses a web-based portal called esymbio. The portal facilitates information retrieval by providing users with personalised access to knowledge and access to networks of experts.

    Within the Nowgen Network, virtual communities of interest are being formed to support inter-institutional and interdisciplinary initiatives. Initially, a number of pilot communities are being established to focus on clinical, ethical, legal, scientific and educational issues associated with genetics.

    International policy
    US report recommends 29 conditions for mandatory newborn screening
    An expert panel convened by the American College of Medical Genetics (ACMG) has identified 29 conditions for which newborn screening should be mandatory in the USA. The experts have released their recommendations for public consultation. The ACMG report was commissioned by the US Maternal and Child Health Bureau (MCHB) with the aim of introducing uniformity in newborn screening programmes across different US states and assisting the development and implementation of nationally recognised newborn screening system standards and policies. The ACMG was specifically asked to develop recommendations to address:
  • A uniform condition panel (including implementation methodology);
  • Model policies and procedures for state newborn screening programs (with consideration of a national model);
  • Model minimum standards for state newborn screening programs (with consideration of national oversight);
  • A model decision matrix for consideration of state newborn screening program expansion; and
  • Consideration of the value of a national process for quality assurance and oversight.


    Research in Action
    EU project focus
    ENERCA: Helping doctors to help patients with rare anaemias
    Rare anaemias can take many different forms from congenital red blood disorders such as thalassaemias, to congenital defects of erythropoiesis such as sideroblastic anaemias and very rare congenital disorders of iron metabolism. Like many rare diseases, these disorders are characterised by only partially documented diagnosis, treatment that is not always evidence-based, a fragmentary research effort and a lack of sharing of results.

    ENERCA, the European information network on Rare Anaemias, funded under the European Commission’s DG SANCO public health programme, was set up to tackle these problems. Under the motto “a help for the doctor = a help for the patient”, its aim is to update and improve the diagnosis of rare congenital anaemias in the EU through trans-national collaboration between experts, epidemiological monitoring and surveillance, and early warning for clusters of rare anaemias.

    The ENERCA network, which has the support of more than 100 partners spread across 13 EU countries, centres around a website aimed specifically at patients and their families, with information on specialist centres and patients associations available in nine languages, and a database aimed at experts. The secure-access database provides experts with epidemiological data and details of current treatments, genetic counselling and preventative measures. In the future it will also contain a specialised registry.

    The initial project ran for 18 months from 2002 – 2004. A second phase of the project – ENERCA II - is about to be launched. Through the implementation of nine work packages it will build on the progress made in the first stages of the project by:

  • improving cooperation between member states in the diagnosis and treatment of rare anaemias;
  • promoting epidemiological surveillance of emerging congenital rare anaemias by promoting the exchange of information on sickle-cell anaemia and thalassaemia obtained from existing databases or from local neonatal screenings undertaken by each partner, when necessary;
  • promoting the exchange of information using existing European information networks on rare diseases with the aim of creating a European register for rare anaemias;
  • producing guidelines for prevention, diagnosis and clinical management of rare anaemias, accessible through the ENERCA website;
  • developing training courses and e-meetings on rare anaemias;
  • developing an External Quality Assessment for quality assurance and improvement of laboratory diagnostic procedures.

  • Contact ENERCA’s project leader, Dr Joan-Luis Vives Corrons, of the Hospital Clínic i Provincial de Barcelona, for further information.

    New diseases & syndromes
    New diseases and syndromes published on PubMed in June 2005
    3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome
    Am J Hum Genet ; 77(1):154-60 ; July 2005
    Characterisation of a new syndrome that associates Craniosynostosis, Delayed Fontanel Closure, Parietal Foramina, Imperforate A
    Am J Hum Genet ; 77(1):161-8 ; July 2005
    New genes
    New rare disease genes published on PubMed in June 2005
    Mutations in Col4a1 cause perinatal cerebral haemorrhage and porencephaly
    To read more about "Porencephaly, familial"

    Science ; 308(5725):1167-71 ; 20 May 2005
    Heterozygous mutations of OTX2 cause severe ocular malformations
    To read more about "Anophthalmia, clinical"
    To read more about "Microphthalmia"

    Am J Hum Genet. ; 76(6):1008-22 ; June 2005
    Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion
    To read more about "Mitochondrial DNA depletion syndrome"

    Am J Hum Genet ; 76(6):1081-6 ; June 2005
    Mutation analysis of COL9A3, a gene highly expressed in the cochlea, in hearing loss patients
    To read more about "Deafness, nonsyndromic sensorineural recessive, DFNB"

    Auris Nasus Larynx ; 32(2):113-7 ; June 2005
    Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype
    To read more about "Progeria"
    To read more about "Mandibuloacral dysplasia"
    To read more about "Dermopathy restrictive lethal"

    J Med Genet ; 42(6):e36 ; June 2005
    Low expression VEGF haplotype increases the risk for tetralogy of Fallot: a family based association study
    To read more about "Tetralogy of Fallot"

    J Med Genet ; 42(6):519-22 ; June 2005
    Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in Nail-Patella syndrome
    To read more about "Nail-patella syndrome"

    Eur J Hum Genet ; 13(6):789-92 ; June 2005
    Mutations in PIP5K3 Are Associated with Francois-Neetens Mouchetee Fleck Corneal Dystrophy
    Am J Hum Genet ; 77(1):54-63 ; July 2005
    Homozygous Nonsense Mutations in KIAA1279 Are Associated with Malformations of the Central and Enteric Nervous Systems
    Am J Hum Genet ; 77(1):120-6 ; July 2005
    Biotin-Responsive Basal Ganglia Disease Maps to 2q36.3 and Is Due to Mutations in SLC19A3
    Am J Hum Genet ; 77(1):16-26 ; July 2005
    Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations
    Proc Natl Acad Sci U S A ; 102(23):8089-96; discussion 8086-8 ; June 2005
    Identification of a Major Recombination Hotspot in Patients with Short Stature and SHOX Deficiency
    To read more about "Dyschondrosteosis"
    To read more about "Mesomelic dwarfism langer type"
    To read more about "Turner syndrome"

    Am J Hum Genet ; 77(1):89-96 ; July 2005
    New clinical research
    New clinical trials in the Orphanet database
    Phase II study of patients suffering from chronic idiopathic thrombocytopenic purpura

    A multicentric international trial

    An evaluation of efficacy and safety of posterior justascleral administration of Anercortave Acetate for depot suspension (15 mg or 30 mg) versus Sham administration in patients with a risk of developing a choroidal neovascularisation ...

    A multicentric international trial

    To register your interest in participating in a clinical trial visit Orphanet.

    New clinical research published on PubMed in June 2005
    Prediction of survival for patients with bullous pemphigoid: a prospective study
    To read more about "Bullous pemphigoid"

    Arch Dermatol ; 141(6):691-8 ; June 2005
    Childhood overgrowth in patients with common NF1 microdeletions
    To read more about "Neurofibromatosis type 1"

    Eur J Hum Genet. ; 13(7):883-8 ; July 2005
    Clinical and magnetic resonance imaging characteristics of sporadic cerebellar ataxia
    To read more about "Multiple system atrophy"

    Arch Neurol. ; 62(6):981-5 ; June 2005
    Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin
    To read more about "Ulcerative colitis"

    N Engl J Med. ; 16;352(24):2499-507 ; June 2005
    Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy
    To read more about "Gestationis pemphigoid"

    Arch Dermatol. ; 141(6):705-10 ; June 2005
    New therapeutic & diagnostic approaches
    Therapeutic and diagnostic research in rare diseases published on PubMed in June 2005
    Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia
    To read more about "Congenital adrenal hyperplasia"

    Eur J Endocrinol ; 152(6):869-874 ; June 2005
    Quality of life determinants in young women with turner's syndrome after growth hormone treatment: results of the StaTur population-based cohort study
    To read more about "Turner syndrome"

    J Clin Endocrinol Metab ; 90(4):1992-7 ; April 2005
    Cockayne Syndrome : much-cited paper withdrawn from 'Science'
    A 1997 paper by Cooper et al., featuring research on a genetic disorder called Cockayne syndrome, has been withdrawn from the journal 'Science' after three of the paper's authors said that two figures contained invalid data and that the paper's conclusions could no longer be supported. Tony Leadon, the fourth author, a former professor at the University of North Carolina at Chapel Hill, who has previously been found guilty of fabricating findings in his research on DNA repair, refused to sign the retraction. Researchers have so far been unable to replicate the paper's results which linked Cockayne syndrome to defective repair of oxidative damage.
    Science ; 275, 5302, 990-993 ; 14 February 1997

    Prevalence and Surveillance
    Rare Diseases in Numbers
    Eurordis, in partnership with Orphanet, is currently undertaking a bibliographic study on the epidemiology of rare diseases. The study aims to evaluate the prevalence of a number of rare diseases in Europe and, for each of these diseases, to document the age of onset, life expectancy and mode of inheritance.

    Preliminary results from the study were presented at the European Conference on Rare Diseases in June.


    The more the merrier...
    Use OrphaNews Europe’s PartnerSearch if you are looking for partners for your research project, your patients association, or any other form of collaboration relevant to rare diseases and orphan drugs.

    Simply contact OrphaNews Europe and we will publish your request in the next monthly edition.


    Funding opportunities
    DG Research calls for proposals
    Final call for life sciences under FP6
    The European Commission's DG Research has released its updated Work Programme for the Sixth Framework Programme under Priority One on 'Life Sciences, Genomics and Biotechnology for Health'. This Work Programme will provide the basis for the final call for proposals under this priority in the current framework programme, with a deadline for 9 November 2005. The Work Programme includes many research topics relevant to rare diseases, notably under the following headings:

    i) Advanced Genomics and its Applications for Health:

    Multidisciplinary functional genomics approaches to basic biological processes:
  • Functional genomics of autosomal aneuploid syndromes (INTEGRATED PROJECT)

  • Development of new diagnostics:
  • High throughput molecular diagnostics for hereditary diseases (INTEGRATED PROJECT)

  • Development of innovative methods for diagnosis of nervous system disorders (STREP)

  • Development and testing of new preventive and therapeutic tools, such as somatic gene and cell therapies (in particular stem cell therapies, for example those on neurological and neuromuscular disorders) and immunotherapies:
  • Tissue engineering approaches to treating children with birth defects (INTEGRATED PROJECT)

  • Understanding monogenic rare diseases using insight from stem cell lines (STREP)

  • ii) Combating Major Diseases

  • Genetic control of the pathogenesis of diseases based on iron metabolism (STREP)

  • Combating cardiovascular disease, diabetes and rare diseases:
  • Rare inherited neuromuscular disorders: from molecular basis to cutting edge therapies (NETWORK OF EXCELLENCE)

  • Rare disorders of protein folding (STREP)
    (Neurodegenerative disorders, cancers and cystic fibrosis will not be considered for funding)

  • Rare diseases of connective tissues affecting bone and/or cartilage (STREP)

  • Combating cancer:
  • Innovative diagnostic approaches and novel therapies of childhood cancers (STREP)
    (Childhood tumours, such as leukaemia, brain tumours, neuroblastoma, Wilms’ tumor, lymphoma, Rhabdomyosarcoma, retinoblastoma, osteosarcoma and Ewing’s sarcoma will be considered. Proposals should not be restricted to one malignancy only but include several of the above)

  • SME-specific call
    There will also be a specific call for SMEs in which research consortia should aim to have 30-50 % of the requested EC contribution budget going to SMEs.

    Topics relevant to rare diseases under this call include:
  • Development and testing of new preventive and therapeutic tools, such as somatic gene and cell therapies (in particular stem cell therapies, for example those on neurological and neuromuscular disorders) and immunotherapies ( STREPs dedicated to SMEs)

  • Development of in vitro and/or animal models for rare diseases (STREPs dedicated to SMEs).
    Models for rare cancers will not be considered for funding.

  • Budget
    The total budget available for this work programme is 555.6 million euros of which 171 million euros is earmarked for the SME-specific projects

    Deadline for the call for proposals will be 9 November 2005 at 17.00 (Brussels local time).


    Orphan Drugs
    New designations & authorisations in Europe
    June 2005
    At its meeting on 14 and 15 June, the Agency’s Committee for Orphan Medicinal Products (COMP) adopted 5 positive opinions on orphan designation for medicinal products for the following indications:
    - treatment of Duchenne muscular dystrophy
    - treatment of pancreatic cancer
    - treatment of congenital adrenal hyperplasia
    - treatment of Cushing's syndrome secondary to ectopic ACTH secretion
    - treatment of hepatocellular carcinoma

    EMEA COMP opinions in June

    Details of all orphan designations and authorisations granted to date by the European Commission are entered in the Community Register of Orphan Medicinal Products

    21st orphan medicinal product authorised in EU
    In June, a treatment for cataplexy in patients with narcolepsy - Xyrem (sodium oxybate), from UCB Pharma Ltd – became the twenty-first orphan medicinal product to receive a positive opinion on initial marketing authorisation from the EMEA’s Committee for Medicinal Products for Human Use (CHMP).
    New designations & authorisations in USA
    June 2005
    A full list of all US designations and marketing approvals can be found here
    Adopting an orphan. Incentives to develop drugs for rare disorders raise hopes and controversy
    An overview of international initiatives to encourage orphan drug development and discussion of the key problems highlighted by stakeholders.
    EMBO Reports ; 6(6):507-10 ; June 2005

    Ethical, Legal & Social Issues
    European Parliament seminar on human egg trade raises concern amongst scientists
    A seminar entitled 'Human Egg Trading and the Exploitation of Women' held at the European Parliament on 30 June has raised questions in the scientific community about the dangers of treating emotive subjects in the absence of scientific debate.

    Organised by CORE - a public interest group focusing on ethical dilemmas surrounding human reproduction, particularly the new technologies of assisted conception - and hosted by German MEP Hiltrud Breyer, the seminar centred on the problems experienced by women involved in IVF treatment, either as donors or patients.

    However, one of the outcomes of the meeting was a decision to focus further discussion on the endorsement of the subsidiarity principle throughout Member States, with reiteration that no EU funding be directed to embryo research, embryonic stem cell research or human cloning.

    Scientists present at the meeting commented afterwards that they felt excluded from the debate and were concerned that such meetings may lead to political decisions being made based on incomplete information.

    A draft report on assisted reproductive techniques (ART) and genetics has recently been published by the European Society of Human Genetics’ Public and Professional Policy Committee, in collaboration with the European Society of Human Reproduction and Embryology and the Institute for Prospective Technological Studies, one of the seven scientific institutes of the European Commission's Joint Research Centre.

    The draft report entitled 'The interface between medically assisted reproduction and genetics: technical, social, ethical and legal issue' is based on the recommendations formulated by a group of 50 experts including gynaecologists, geneticists, representatives of patients’organisations for infertile couples and hereditary diseases, psychologists, ethicists, lawyers, health policy makers and social scientists who met during a workshop in Sevilla on 31 March – 1 April 2005.

    Direct-to-consumer genetic testing: medicine in the marketplace
    With increasing numbers of genetic tests now available on-line, by-passing conventional medical channels, there is a real risk that consumers may make poor health decisions based on test results and without the benefit of genetic counselling or other medical advice.

    In April 2005, the Genetics & Public Policy Center at Johns Hopkins University in the USA convened a public meeting to hear from industry spokespersons, ethicists, doctors and policy analysts to explore the commercial, legal, medical and ethical issues raised by direct-to-consumer marketing of genetic tests.

    A video stream of the meeting's presentations is now available.

    In November 2004, the French national consultative ethics committee (CCNE) published an opinion on 'Problems connected to marketing self-test kits for HIV screening and diagnosis of genetic disease'. In the latest edition of the Committee's journal, the 'Cahiers du CCNE' (in French), a number of experts comment on this opinion and its implications.

    Research and rare genetic differences: Frequently Asked Questions
    A recent joint publication by the UK’s Genetic Interest Group, the Oxford Genetics Knowledge Park and the Ethox Centre at Oxford University highlights and answers some of the common questions asked by research ethic committees (RECs) when looking at research proposals relating to genetic disorders.

    In research into rare inherited disorders, the process of securing ethics committee approval for a proposed study can sometimes prove disproportionately burdensome and this can, in some cases, undermine the viability of good quality research. This is particularly the case where such research is funded by patient groups.

    The result of a series of workshops involving patients, researchers, research funders, members of research ethics committees, ethicists, social scientists and medical lawyers, the booklet contains a list of frequently asked questions that are indicative of the issues which RECs have found challenging when evaluating proposals.

    Medical research participants: is more protection needed?
    How effective is the EU’s Data Protection Directive at safeguarding the fundamental rights and freedoms of medical research subjects?

    PRIVIREAL, an EU Fifth Framework Programme project involving 49 individual and institutional members in 27 countries, including new EU Member States, Candidate Countries and Norway, led by researchers at the Sheffield Institute of Biotechnological Law and Ethics, University of Sheffield (UK), was set up to look into this question. The project leaders presented their findings at a meeting in Brussels last month, and suggested that in some cases not enough is being done in Member States to protect the rights and freedoms of people involved in medical research programmes, and that more effort is needed to communicate this to national ethics committees responsible for reviewing research proposals.

    “Medical research is vital for the continued health of the population and arguably could be afforded exemptions to some regulations to facilitate this improvement in health. It is an important part of any business economy but this means that it is tempting to relax provisions relating to the fundamental rights and freedoms – especially privacy – of individuals too much”, says David Townend, one of the Sheffield researchers, in an interview for the EC research website.


    News from the Patients Associations
    Bringing liberty through dance: the Psico Ballet experience
    One of the highlights of the European Conference on Rare Diseases held in Luxembourg last month was the evening performance by the Fundación Psico Ballet Maite León from Madrid at the Grand Théâtre du Luxembourg.

    This troupe of dancers is made up of children and adults with different forms of disability who train together at the Fundación's centre in Madrid. The Fundación was created in 1986 by choreographer Maite León Fritsch, herself the mother of a handicapped child. She created a special method of dance to enable her students to create beautiful and moving performances characterised as much by their professionalism as by their creativity and artistic grace.

    The Fundación has won many international awards for its contribution to the arts and to the integration of disabled people and its dancers regularly participate in events across Europe.

    Fundación Psico Ballet Maite León

    Eurordis update
    Rare Diseases: understanding this Public Health Priority
    Eurordis has produced a draft paper for consultation entitled “Rare Diseases: understanding this Public Health Priority”. The document will act as a founding text in order to define the concept of rare diseases as an instrument for public health policy. It aims to clarify some of the concepts related to rare diseases such as ‘rarity’ and to describe some of the specific needs of rare disease patients and their families.

    The draft document was distributed at the European Conference on Rare Diseases in June and the consultation is open until 30 August 2005.

    New European Associations
    Pulmonary Hypertension Association launches European newsletter
    PHA Europe, the European network of national Pulmonary Hypertension Associations, has just launched a European newsletter. PHA Europe was formed last year with the aim of furthering the interests of PH patients in Europe.
    Zoom on...
    The PID model - stronger together
    The engagement of the European primary immunodeficiencies (PID) community and their international partners to get PIDs onto EU health policy agendas provides a compelling argument for the importance of networking in rare diseases.

    PIDs are not a single disease. They cover a huge range of inherited disorders of the immune system, over 100 of which have been classified by the World Health Organisation. It is estimated that 70-90% of these disorders are currently under-diagnosed yet there is published evidence that early diagnosis and optimal treatment of PIDs results in both health economic and quality of life benefits in children and adults. Most primary immune deficient patients require life long therapies including intravenous gammaglobulin infusion, aggressive antibiotic therapies, or, for the most severe ones, bone marrow transplantation.

    A number of European and international organisations, representing patients, doctors, nurses and researchers have been working together over the past decade to improve the awareness, care and research regarding PIDs, ensuring the active participation of all those implicated. Every two years the European Society for Immunodeficiencies (ESID) , the International Patient Organisation for patients with Primary Immunodeficiencies (IPOPI), and the International Nursing Group for Immunodeficiencies (INGID), organise a conference to share the latest developments in the field and to share partner experiences. This joint venture ensures that messages on PIDs remain coherent and that they receive a wide dissemination. The next joint meeting will be held in Budapest, Hungary from the 4 – 7 October 2006.

    The same organisations, along with the European Federation of Immunological Societies (EFIS), and the US-based Jeffrey Modell Foundation have recently formed a working group with the aim of alerting EU and national health policymakers to the public health issue posed by PIDs. Thanks to active campaigning and fund-raising in the USA by the Jeffrey Modell Foundation, PIDs have been treated as a key public health issue there for some time – reflected in the annual budgets assigned to combating PIDs by US Congress ($2M in 2004). Hoping to achieve a similar level of awareness and support in Europe, the European working group launched a series of political awareness-raising activities in 2004, including a hearing on PIDs within the European Parliament in March, a European Parliament Resolution on PIDs in May, proposed by the MEP Guiseppe Nistico, and a meeting between the European Commission and four representatives of the PID community in November. This year the EU PID community presented a joint poster at the European Conference on Rare Diseases in Luxembourg and has made a joint submission to the EU’s public health programme under the 2005 work plan.

    “There is documented evidence of improved diagnosis rates for PIDs resulting from tried and tested awareness and education campaigns. Wider development and expansion of these campaigns in the EU could prove to be excellent case studies for the wider rare disease community where under-diagnosis is a common problem”, says Dr Ann Gardulf, European President of the INGID and member of the working party. She hopes that the European PID community can be seen as a model of successful international collaboration between stakeholders in a group of rare diseases, that other organisations could usefully learn from.

    Read the IPOPI strategic plan 2005-2009

    Read the latest report from the International Union of Immunological Societies expert committee on Primary Immunodeficiency Diseases


    Courses & Educational Initiatives
    Educational resources & materials
    Telling Stories
    A new website is being created to help nurses, health visitors and midwives learn about genetics and understand the effect genetic conditions have on people’s lives.

    The project, called ‘Telling Stories: Understanding Real-Life Genetics’, will collect around eighty stories from individuals and families who are affected with different genetic conditions, as well as health professionals with a particular story to tell about their experience in caring for people with a genetic condition. The stories will be collected as video clips, sound recordings and written accounts of people’s experiences.

    Funded by the Wellcome Trust, ‘Telling Stories’ is a joint initiative of the UK’s University of Glamorgan, University of Plymouth and the Genetic Interest Group.


    What's on where?
    In September
    European Society of Pathology congress: pre-meeting of the Pulmonary Pathology working group
    Theme: Part of this meeting will be dedicated to rare pulmonary diseases and will discuss new and old cases from the collection of the 24 European Centres for Pulmonary Pathology which comprises more than 800 rare disease samples. This material is used for training doctors and educating young pathologists in the diagnosis of these diseases. See the EC project on Rare Lung Diseases website for further details.

    Date: 2-3 September 2005
    Venue: Paris, France

    4th European Meeting of the International Society for Neonatal screening
    Theme: What are the best strategies for the screening of clinically relevant diseases?

    Date: 5-6 September 2005
    Venue: Paris, France

    42nd Annual Symposium of the Society For The Study Of Inborn Errors Of Metabolism
    Theme: Treatment of Inborn Errors of Metabolism. Plenary sessions on Cell and Organ transplantation, Genetic therapy, Enzyme and Substrate deprivation therapies, and Nutrition therapy and medication.

    Date: 6-9 September 2005
    Venue: Paris, France

    International Conference On Confidentiality And Privacy In Healthcare In Europe
    The Workshop will partly be focussed on the European Standards on Confidentiality and Privacy in Healthcare among Vulnerable Patient Populations developed by the EuroSOCAP Project and will also include panel discussions and plenary sessions devoted to general and specific consideration of issues of confidentiality and privacy in healthcare in a European context.

    Date: 8-9 September 2005
    Venue: Brussels, Belgium

    Access to Quality Testing for Rare Diseases
    This conference is a collaborative effort of the National Institutes of Health, the Centers for Disease Control and Prevention, the Health Resources and Services Administration, the American Society for Human Genetics, the American College of Medical Genetics, the Genetic Alliance, the Society for Inherited Metabolic Disorders, the National Organization for Rare Disorders, and Emory University Department of Human Genetics to address the growing public need for improvement in availability, accessibility, and quality of genetic and other diagnostic laboratory testing for rare diseases and conditions.

    Date: 26-27 September 2005
    Venue: Rockville, MD, USA

    Nord Annual Conference
    Theme: Access to Medical Care: Navigating Medicare, Medicaid, and Private Insurance

    Date: 30 September - 2 October 2005
    Venue: Arlington, Virginia, USA

    In October
    EFGCP Children's Medicines Working Party First Annual Conference
    A conference organised by the European Forum for Good Clinical Practices (EFGCP), Europe's think-tank for considering the ethical, regulatory, and scientific framework of clinical research in Europe.
    Theme: How will the EU Pediatric Legislation Stimulate Paediatric Research?

    Date: 20 October 2005
    Venue: Brussels, Belgium

    EPPOSI Workshop On Partnering For Rare Disease Therapy Development
    Organised by EPPOSI (European Platform for Patients' Organisations, Science and Industry), in association with US partners, NORD and the NIH, this international event aims to provide a forum for discussion between political decision makers, healthcare providers, patient representatives and industry from several regions of the world, on the research and development of innovative health products and health services and their impact on the quality of life of patients, with a focus on rare diseases.

    Date: 25-27 October 2005
    Venue: London,UK

    XIII Annual Congress of the European Society of Gene Therapy (ESGT)
    The meeting will cover all aspects of gene therapy, from bench to bedside. Topics will include cancer, stem cells, cardiovascular disease, infectious disease, skeleto-muscular systems, respiratory issues, promoter targeting and genome edition, siRNA, miRNA, zinc fingers, and recent advances in viral and non-viral vector development.

    Date: 29 October - 1 November 2005
    Venue: Prague, Czech Republic

    In November
    Value and risks of genetic data collections
    Date: 10-11 November 2005
    Venue: Geneva, Switzerland

    In December
    NICE 2005: Health and Clinical Excellence
    Health and Clinical Excellence is the leading event for senior health care directors and managers, clinicians and policy makers. It profiles outstanding national and international examples of health improvements and clinical excellence. It provides essential guidance to practitioners, explores the challenges of public health and highlights research and development initiatives.

    Date: 7-8 December 2005
    Venue: Birmingham, UK

    In 2006
    Genetic Analysis: from model organisms to human biology
    Organised by the Genetics Society of America, the goal of this meeting is to emphasise the value of model organisms in understanding biology. The meeting has been designed to highlight both human and model organism genetics in a complementary way.

    Date: 5-7 January 2006
    Venue: San Diego, USA


    Orphanews Europe, the newsletter of the Rare Diseases Task Force
    Orphanews Europe is supported by the European Commission's DG SANCO
    and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Dr Ségolène Aymé
    Editor: Sally Goodman
    Contact Us
    Editorial Board: Ségolène Aymé, Aurélie Bedin, Catherine Berens, Helen Dolk, Anders Fasth, Edmund Jessop, Yann Le Cam, Jordi Llinares-Garcia, Helmut Popper, Elena Prats, John Ryan, Janos Sandor, Arrigo Schieppati, Rumen Stefanov, Domenica Taruscio, Joan Luis Vives Corrons
    For more information on the Rare Diseases Task Force
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