23 September 2005 print
Task Force Update
Spotlight on...
EU Policy
National Policy News
Research in Action
Orphan Drugs
Ethical, Legal & Social
Courses & Education
Press & Publications
What's on?
Subscribe / Unsubscribe

Creating a win-win climate for orphan drugs
Over the next couple of months the European Commission will launch a public consultation exercise to assess stakeholder views on five years of European orphan drugs regulation, ahead of its report to the European Parliament on the impact of the Regulation, due in early 2006. Formal feedback on the Regulation’s impact (see Spotlight) has generally been positive. In addition, the recent European Parliament vote in support of the proposed draft paediatric medicines directive, inspired in part by the success of the orphan legislation, is a sign that government decision-makers are willing to work with industry to create a win-win climate for patients and drug developers alike.

The inventory of national incentives to support rare diseases and orphan drugs is currently being updated, in line with Article 9 of the Regulation. This inventory will be published by the end of the year and should give an idea of which member states have evolved over the five years of the Regulation in their support of rare diseases and orphan drugs. However, the early results of this update have made clear that there is still much room for progress. In spite of the positive impact of the Regulation at the European level, national governments have, more than ever, a responsibility to ensure that orphan drugs are made available to those in need of them and that rare diseases, and those suffering from them, are not relegated to the bottom of their list of priorities. In addition, the ongoing update has highlighted the difficulty of identifying central points of information on rare disease initiatives in each country, reinforcing the argument for more co-ordinated networking between those working in the field in Europe, whether patients, industry, academics or government.

This newsletter is one way of ensuring that information about initiatives in support of rare diseases in Europe are shared across the community – but only if you let us know about them…

Deadline for submissions

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

The next edition will appear in mid-October.
Deadline for the next issue is
7 October 2005.


Task Force Update
Final report of Third Rare Diseases Task Force meeting
The final report of the third meeting of the Rare Diseases Task Force, held on 20 June 2005 in Luxembourg, is now accessible on the RDTF website (under meetings/events).

The next meeting will be held in Luxembourg on 14 December 2005.

Working groups
Recommendations on European Centres of Reference
The RDTF expert group on European centres of reference for rare diseases met on 12 September in Paris to discuss draft recommendations to the European Commission’s High Level Group on Health Services and Medical Care on the issue of European centres of reference.

These recommendations will be the subject of discussion at the next meeting of the High Level Group on 29 September and will inform the Commission’s decision on possible future funding for the establishment of European centres of reference and the support of existing networks of expert centres in rare diseases.

These recommendations will be made available on the RDTF website (under working groups), after the meeting on 29 September.


Spotlight on...
...Five years of European Orphan Drugs legislation
The EU orphan drug legislation (Regulation 141/2000 on orphan medicinal products) celebrates its five year anniversary this year. In support of Article 10 of the Regulation, which foresees a general report on experience acquired and public health benefits obtained as a result of the Regulation, the European Medical Agency’s Committee for Orphan Medicinal Products (COMP) established within the EMEA since March 2000 has issued a report to the European Commission reflecting upon their 5 years of experience.

In its report the COMP concludes that the EU orphan drug legislation has been successfully applied without any major difficulties, achieving outstanding results and public health benefits. Together with the Commission and in consultation with stakeholders and interested parties, the COMP has developed appropriate guidance to establish a sound EU process to designate orphan medicinal products eligible for incentives as provided by the legislation.

The COMP report will contribute to the European Commission’s general report on the orphan legislation, due in January 2006, after a broader public consultation exercise this Autumn. As part of this consultation, and at the request of the Commission, the EBE (Emerging Biopharmaceutical Enterprises) and EuropaBio (the European Association for Bioindustries) have commissioned a joint Economic Impact Assessment of the Regulation, to be published in due course, and which will also contribute to the Commission’s final report.

COMP conclusions and recommendations on EU Policy on Orphan Medicinal Products

While the COMP considers that the current legislative framework for orphan medicinal products is suitable overall to achieve public health benefits for patients suffering from rare diseases, it has identified a number of policy areas that require strengthening. In its report, the COMP makes the following recommendations to stimulate and foster EU policy on orphan medicinal products, through:
  • Supporting the European Medicine Agency proposal for a new policy on fee reductions and increased EU Special Contribution.
  • Recognising that this Regulation is resource intensive for EMEA and for COMP members. Thus, the long-term sustainability of the Orphan legislation should be supported through appropriate financial resources taking into account the contributions of EMEA, the National Competent Authorities and Patient groups
  • Providing further guidance on the criterion of insufficient return on investment and on the definition of « sufficiently profitable » to review market exclusivity at 6 years. This may imply amending the current Commission Regulation (EC) N° 847/2000 of 27 April 2000 (medical plausibility, criterion of insufficient return on investment) and the Commission Communication of July 2003 (market exclusivity, sufficient profitability).
  • Ensuring that designated orphan medicinal products that are already authorised nationally or through mutual recognition are considered in the same way as non-orphan products and can continue with further national authorisations (Annex of Regulation (EC) N° 726/2004).
  • Reinforcing orphan medicinal product research through the 7th Framework Programme, by highlighting rare diseases as a research priority and further recognising as a priority the need to fund the non-clinical and early clinical (phases I and II) research of designated orphan medicinal products through research grants.
  • Consolidating regular information exchange and policy coordination between COMP/EMEA, DG Enterprise, DG Research and DG Sanco.

  • In addition, the COMP advises the Commission to take appropriate actions:
  • To increase the visibility of those medicinal products authorised for rare diseases prior to the implementation of the EU orphan legislation. The Committee supports the EuroPharm initiative as a tool towards that aim.
  • To encourage Member States to actively adopt national incentives (fee waivers, research grants, tax deductions, pricing and reimbursement supportive policy, national orphan drug steering committee) to support the development of and access to orphan drugs.
  • To further explore co-ordination of transparency measures between Member States to speed up and ensure orphan drug availability to patients.

  • Orphan drugs in numbers

    Between April 2000 and April 2005:

  • 458 applications for orphan designation were submitted to the EMEA
  • more than 260 products were designated, by April 2005, relating to over 200 different rare conditions
  • 22 products have gone on to receive a marketing authorisation (20 of those through the centralised procedure at the EMEA, 2 through national procedures)
  • 90% of rare conditions, for which a medicinal product has received an orphan designation, have a low prevalence of less than 3 in 10,000
  • 43 % of these occur in less than 1 in 10,000
  • 69 % of positive COMP opinions recommending designation have been based on the criterion of significant benefit
  • 54 % are intended for paediatric use
  • 21% of the products which have been the subject of a designation application are biotech products and emerging therapies such as anti-sense, gene therapy and cell therapy

    ...with Yann Le Cam, Vice-Chair of the EMEA Committee for Orphan Medicinal Products
    Yann Le Cam is Chief Executive Officer of EURORDIS, the European Organisation for Rare Diseases. He is a patients’ associations advocate who has dedicated the past 17 years to professional and personal commitment to health and medical research non-governmental organisations in France, Europe and the United States in the fields of cancers, HIV/AIDS and rare diseases.

    He has been a member of the COMP since it was set up in 2000 and is co-chair of the COMP Working Group of Interested Parties.

    OrphaNews Europe: What has been the impact of the patient groups involvement in the decision-making of the COMP?

    YLC: The COMP was pioneering in that patients were involved for the first time in a decision-making committee at European level. Their role has become progressively more important over time by providing a special focus on the public health aspects of the committee’s work. For the first time, candidate drugs were looked at for their potential use in day-to-day life and in a therapeutic strategy and not only from a regulatory and scientific point of view.

    One of the key achievements has been that increased participation by patients has enhanced the transparency of the COMP and the EMEA. More information has become available, such as the public summary of opinions for designated drugs, and an on-going dialogue has been established through a series of workshops. Patient participation has also contributed to the recognition of the specific expertise that patient groups can bring to scientific and regulatory debate. Over the five years, 45 different patient representatives have participated in the COMP’s activities.

    Having patient representatives at the EMEA has also helped to structure the rare diseases patient movement in Europe and to promote the dialogue with all interested parties, particularly industry and national authorities.

    Orphanews Europe: Is there still more that can be done to increase transparency?

    YLC: The development of each orphan drug needs to be followed and this information made available to patients and professionals. We would like to see more information made available from the studies that take place after orphan drug designation up until the marketing authorisation, including the final results of studies, either positive or negative. This lack of transparency is found in clinical research generally but its impact is greater in rare diseases, where unmet medical needs are high and resources are very limited. There is a risk, however, of ending up with too much information and not being able to extract what is useful.

    Read the full interview with Yann Le Cam


    EU Policy News
    DG Research
    Commission publishes Strategic Research Agenda for Innovative Medicines Initiative
    The Technology Platform for innovative medicines, established under the European Commission’s Sixth Framework Programme for Research, has published a draft strategic research agenda that aims to address current bottlenecks in the biomedical research and development process and accelerate the development of safe and effective new medicines.

    Four key bottlenecks in the biomedical R&D process have been identified, and the strategic research agenda structured in such a way as to address them by encompassing the whole path from discovery of a new drug target to the validation and approval of the final compound.

    The four key pillars of the agenda aim at improving:
  • the predictivity of safety evaluation
  • the predictivity of efficacy evaluation
  • knowledge management
  • education and training

  • The main ambition of the research agenda is to coordinate investments in the drug development process and achieve a critical mass of stakeholders and resources. In order to achieve this, the SRA foresees the creation of a separate legal entity financed equally by the Commission and the biopharmaceutical industry. Recommendations include the creation of a European centre for drug safety, which will coordinate research needs in safety sciences.

    The document concludes that for an initial period of seven years, annual funding of 440 million euro would be needed in order for the new entity to implement the research agenda’s recommendations.

    Clinical trials in small populations : public consultation paper
    The EMEA’s Committee for Medicinal Products for Human Use (CHMP) Efficacy Working Party has produced a discussion paper on the problems associated with clinical trials when there are very few patients available to study.

    The paper, prepared by the CHMP Efficacy Working Party (EWP) in joint collaboration with members of the Scientific Advice Working Party (SAWP), the Committee on Orphan Medicinal Products (COMP) and the Paediatric Expert Group (PEG) outlines strategies for methodological approaches to trials that may be more appropriate for trials in small populations than more commonly used approaches.

    However, it also underlines the dangers of drawing general conclusions from specific cases and emphasises that care must be taken to follow established guidelines for the conduct of clinical trials whenever possible. Methods to increase the efficiency of the design and analysis of trials are also applicable for studies in large populations but are not often used because of increased complexity.

    The working party concludes that there are no special methods for designing, carrying out or analysing clinical trials in small populations but there are, however, approaches to increase the efficiency of clinical trials. Further, some methodological approaches, not acceptable in large trials, may be considered acceptable for trials in small and very small populations. The need for statistical efficiency should be weighed against the need for clinically interpretable results.

    The paper is currently subject to public consultation. Any comments on the Guideline should be sent to the EMEA EWP Secretariat by e-mail or by fax: +44 20 74 18 86 13 by the end of September 2005

    Draft guideline on pharmacovigilance for medicines used in children
    The European Medicines Agency (EMEA) has launched a consultation period on a draft guideline on the conduct of pharmacovigilance for medicines used by the paediatric population, children from birth to 18 years of age. This is the first guideline to focus exclusively on the issues of safety of medicines in children. The EMEA is consulting not only on reporting of adverse drug reactions in children, but also on the possible need for studies designed to follow the long-term safety of medicines in children.

    According to the European Commission, more than 50% of medicines used to treat children are prescribed on an unlicensed or ‘off-label’ basis because they have not been adequately tested and/or formulated and authorised for use in children. Differences in age and the stage of growth and development during childhood mean that children may experience adverse drug reactions that vary in nature, type and severity from those seen in adults. In addition to under-reporting of reactions, off-label use may increase the occurrence of adverse drug reactions. The guideline aims at strengthening the pharmacovigilance system for all medicines used in children, whether specifically authorised for such use or not.

    The European Commission proposed new legislation in September 2004 that aims to stimulate the research, development and authorisation of medicines to treat children. The proposed regulation also contains a number of provisions for pharmacovigilance and the EMEA draft guideline is preparatory work with a view to implementing the regulation once it comes into force.

    Comments should sent to Dr Panos Tsintis, Head of Sector Pharmacovigilance and Post-Authorisation Safety & Efficacy of Medicines by e-mail or by fax: +44 20 7418 8668 by 31 January 2006

    European Parliament
    European Parliament adopts Regulation on Medicinal Products for Paediatric Use
    In its plenary session on 7 September 2005, the European Parliament voted, with an overwhelming majority, in favour of the a draft paediatric medicines directive to stimulate research and development of medicines for children.

    As an incentive to increase research and development of medicines for children, drug companies will be granted a six-month extension of their patent but they will be obliged to run clinical trials involving children before authorisation of the drugs. A revision clause sets out that the length of the patent extension be re-evaluated six years after the regulation enters into force.

    The Parliament has also asked that the European Medicines Agency (EMEA) establish a network of researchers to avoid duplicating research or tests on children and a Paediatric Committee to coordinate the paediatric medicines regulation and activities.

    In addition they call for the creation of a special EU programme for research into medicines for children, to be called MICE (Medicines Investigation for the Children of Europe).

    Read the position paper from Eurordis (the European Organisation of Rare Diseases)

    Read the position paper from Europabio (the European Association on BioIndustries)


    National & International Policy Developments
    Policy developments in EU member states
    German ethics committee recommends genetic testing for civil servants
    Germany’s National Ethics Council, an advisory committee of the German government, has recommended that there should be a new law to safeguard against genetic discrimination of employees in Germany. But critics say the guidance, published in a report on 16 August 2005, is unclear on what time span prognostic tests should cover.

    The committee’s chairwoman said that genetic tests should not be routinely used, but should only take place if the results have an impact on the health of the employee in the next five years and endanger their suitability for the job. They should be considered for civil servants who are in safe, lifelong jobs. The council’s recommendation also concerns other predictive medical tests such as blood tests, x-ray examinations, and magnetic resonance imaging.

    Employers in Germany currently have the right and duty to enquire about the present state of health of a future employee and can ask for a medical examination. Critics say that the latest recommendation opens the door for genetic testing because the time span of five year prognosis for an impact of serious health is not clearly defined. The government had already agreed in principle to forbid any predictive genetic testing but the law was not debated because of the pending elections.

    BMJ ; 331;475 ; 3 September 2005
    UK: Public consultation on embryo screening for lower penetrance conditions
    The UK’s Human Fertilisation and Embryology Authority (HFEA) is seeking the public’s views on the appropriateness of using fertility treatment technology to screen out lower penetrance genetic disorders such as HNPCC (a type of inherited bowel cancer).

    Embryo screening using preimplantation genetic diagnosis (PGD) is already used in the UK to enable parents with a family history of serious conditions, such as cystic fibrosis and Huntington’s disease, to avoid passing the faulty gene which leads to their condition on to their children. The current consultation exercise will focus on those disorders where the conditions are not fully penetrant, meaning that not all carriers of the faulty gene will develop the condition. Lower penetrance conditions often affect people in later life and have a penetrance of between 30 and 90%.

    The HFEA wants to hear the views of patients, carers and representatives of affected families, staff in treatment centres, disability groups, parliamentarians, academics and the wider public so as to build a consensus on the issue and balance the interests of the many groups involved.

    British Medical Association warns against unregulated screening
    The British Medical Association (BMA) has published a report on population screening and genetic testing. In the document, published on 23 August 2005, the BMA recommends that the UK government addresses the issues of unregulated and ad hoc screening, improves information available about formal screening programmes - those that it describes as having a clear national policy, based on sound evidence and with explicit quality standards and quality assurance mechanisms in place - and that the government works with the Association of British Insurers to ensure that genetic screening does not unfairly discriminate against people.
    Policy developments in EU candidate countries
    Bulgarian orphan drugs regulation
    The Bulgarian orphan drugs regulation, based on the EU legislation (Regulation EC 141/2000, will come into force on 31 December 2006, one day before the expected accession of Bulgaria into the EU. The Bulgarian orphan drugs regulation foresees quicker registration (two months) of orphan drugs, already approved by the EMEA’s Committee on Orphan Medicinal Products.
    Other European news
    Eastern European conference on rare diseases: presentations on website
    Presentations from the first Eastern European conference on rare diseases, held in Plovdiv Bulgaria on 27 May 2005 are now accessible on the conference website. A media report on the event is also available, illustrating the high level of interest in the subject of rare diseases shown by the Bulgarian press, TV and radio.
    International policy
    US: FDA Guidance on Gene Therapy Clinical Trials
    The US Food and Drugs Agency has recommended that participants in gene therapy trials be followed for 15 years, unless the risk of delayed adverse events is low. Even then, sponsors should continually assess the participants' risk for delayed events.

    The FDA’s recommendations, published in August as draft guidance for industry sponsors of gene therapy trials, give guidance on the design of studies to include the collection of data on delayed adverse events in participants who have been exposed to gene therapy products.

    A Framework to Assess the Risk of Gene Therapy-Related Delayed Adverse Events is proposed and long-term follow-up observations of trial participants advised if the assessment shows that high risks are associated with the gene therapy product used in the trial.

    Special recommendations on follow-up are proposed for those patients who have received retroviral vectors, following the case of a number of children with X-linked Severe Combined Immunodeficiency developing leukaemia as a result of receiving haematopoietic cells that had been modified ex vivo with a retroviral vector in a pre-clinical trial in France. In particular, the guidance advises that patients and their families are made aware, in lay terms, of the possible risks of adverse events in all informed consent documents.


    Research in Action
    EU project focus
    Eugindat: European genomics initiative on disorders of plasma membrane amino acid transporters
    Primary Inherited Aminoacidurias (PIA) are rare diseases involving defects in renal absorption of amino acids. In cystinuria, for example, an autosomal recessive disorder, the kidneys do not adequately reabsorb certain amino acids (cystine, lysine, ornithine and arginine) during the filtering process, resulting in their excess excretion and the formation of painful crystals or stones in the kidney, urethra, or bladder.

    The Eugindat project, funded under the EC’s 6th Framework programme (EU project number: LSHM-CT-2003-502852) aims to elucidate the genetic and molecular basis for these diseases and in doing so, develop new therapeutic strategies for their treatment.

    Led by Dr Manuel Palacín of the University of Barcelona, the three-year Eugindat project brings together the expertise of 19 partners from 5 European countries and Israel, in a multidisciplinary approach integrating genetics, biochemistry, genomics, physiology, structural biology, drug development and clinical research. Two SMEs are also involved in the project.

    One of the main objectives of the project is to develop a clinical and genetic description of Primary Inherited Aminoacidurias with the generation of a European database for PIA. This will include the study of candidate genes for cystinuria, dicarboxylic aminoaciduria, Hartnup disorder and iminoglycinuria. Information from the PIA database will be made available, at different levels of accessibility, for patients and patient associations, health professionals, contributing professionals and Eugindat members.

    In addition, project partners will be looking at the molecular structure of relevant transporters for PIA and renal reabsorption of amino acids using 2D and 3D protein crystallography techniques, and completing a functional genomic study of these transporters using cellular and knockout mice models and the identification of polymorphisms in genetically isolated human populations.

    By identifying genes and genetic loci that affect cystinuria lithiasis, they hope to eventually explain gender and individual variability in the formation of stones in the renal system of patients with cystinuria and to develop new therapeutic strategies for this disease.

    One form of PIA disease, lysinuric protein intolerance (LPI), is associated with life-threatening complications of the immune system and can also affect the hepatic system. The Eugindat project aims to test new therapeutic approaches to treat the most severe effects of LPI once the mechanisms of pathology of these complications have been identified.

    Although the Eugindat project deals principally with kidney function, the creation of mouse models of amino acid and peptide transporter defects will also have scientific impact in other areas, such as nutrition, cachexia (severe malnutrition associated with chronic illness) and certain disorders of the central nervous system, where these transporters play an important role.

    Scientists, clinicians, patient organisations and institutions will be invited to attend a public meeting to be held in Rome in Spring 2007 to discuss the final results of the Eugindat project. For further details contact the Eugindat project office.

    OrphanPlatform: first activity report published
    OrphanPlatform is the European Platform of Integrated Information Services for the coordination of rare disease research and early clinical trials in Europe. It involves stakeholders from research, SMEs and patient organisations.

    Funded for two years under the European Commission’s Sixth Framework Programme for Research (contract no: LSSM-CT-2004-503246), the project aims to develop information tools to address in a comprehensive and integrated approach the set of factors that currently affect research on rare diseases and its coordination.

    A platform of services in 11 European countries is being developed in the pilot phase in order to propose an extension to the 25 European countries in 2006. Ultimately, the goal is to convert scientific developments in the field of rare diseases into diagnostic tools and therapies as quickly as possible.

    During the first year of OrphanPlatform, over 400 research projects and clinical trials have been entered into the Orphanet database.

    The service which allows patients to register as volunteers for participation in clinical trials has registered 457 patients so far, suffering from 230 distinct diseases. These patients are from 11 countries (Austria, Belgium, Denmark, France, Germany, Italy, Luxembourg, Spain, Switzerland, United Kingdom, and Sweden).

    OrphanXchange, the database of research projects seeking partnership with Industry has received 1580 requests. 70% of the requests are performed by registered users of which 50% come from the private pharmaceutical sector, the major targeted public for the database. There are 130 registered users comprising 50% Pharma-Biotech-Venture Capital-Consulting, 36% Public research/Healthcare, 7% patient support groups, and 7% of other users, coming from 21 registered visiting countries: (Austria, Belgium, Bulgaria, Canada, Denmark, Estonia, Finland, France, Germany, Ireland, Italy, Japan, Malta, Netherlands, Pakistan, Portugal, Sweden, Switzerland, United Kingdom, United States). The visits by registered users have induced 47 contact requests of which 29 were accepted by the researcher. A survey of the outcome of these requests is planned for the second half of 2005.

    A first activity report, outlining progress made in the pilot phase of the project, has recently been published.

    New diseases & syndromes
    New diseases and syndromes published on PubMed from July to September 2005
    Achlorhydria, parietal cell hyperplasia, and multiple gastric carcinoids: a new disorder.
    Am J Surg Pathol. ; 29(7):969-75 ; July 2005
    Hereditary congenital unilateral deafness: a new disorder?
    Ann Otol Rhinol Laryngol. ; 114(4):332-7 ; April 2005
    A Mutation in SNAP29, Coding for a SNARE Protein Involved in Intracellular Trafficking, Causes a Novel Neurocutaneous Syndrome Characterized by Cerebral Dysgenesis, Neuropathy, Ichthyosis, and Palmoplantar Keratoderma.
    Am J Hum Genet. ; 77(2):242-51 ; August 2005
    Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of heart-hand syndrome?
    Clin Genet. ; 68(2):155-60 ; August 2005
    Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance?
    J Oral Pathol Med. ; 34(7):444-6 ; August 2005
    Sensorineural hearing loss, early greying, and essential tremor: a new hereditary syndrome?
    Otolaryngol Head Neck Surg. ; 133(1):94-9 ; July 2005
    X-linked Dominant Chondrodysplasia With Platyspondyly, Distinctive Brachydactyly, Hydrocephaly, and Microphthalmia
    Am J Med Genet A. ; 136(4):307-12 ; August 2005
    New genes
    New rare disease genes published on PubMed from July - September 2005
    Mutations in FLNB cause boomerang dysplasia
    To read more about "Boomerang dysplasia"

    J Med Genet. ; 42(7):e43 ; July 2005
    Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)
    J Med Genet. ; 42(7):551-7. ; July 2005
    Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.
    Nat Genet. ; 37(7):733-8. ; July 2005
    TACI is mutant in common variable immunodeficiency and IgA deficiency
    Nat Genet. ; 37(8):829-34 ; August 2005
    Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans
    Nat Genet. ; 37(8):820-8 ; August 2005
    New clinical research
    New clinical research published on PubMed from July to September 2005
    The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2
    To read more about "Neurofibromatosis type 2"

    J Med Genet. ; 42(7):540-6 ; July 2005
    Correction of glycogen storage disease type II by an adeno-associated virus vector containing a muscle-specific promoter
    To read more about "Glycogen storage disease type 2"

    Mol Ther. ; 11(6):889-98. ; June 2005
    Different patterns of magnetic resonance imaging atrophy for frontotemporal lobar degeneration syndromes.
    To read more about "Frontotemporal lobe dementia"

    Arch Neurol. ; 62(7):1106-10. ; July 2005
    New and reliable MRI diagnosis for progressive supranuclear palsy
    To read more about "Supranuclear palsy, progressive"
    To read more about "Parkinson disease, genetic types"
    To read more about "Multiple system atrophy"

    Neurology ; 64(12):2050-5 ; 28 June 2005
    A new screening tool for cervical dystonia
    To read more about "Focal dystonia"

    Neurology ; 64(12):2046-9 ; 28 June 2005
    Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil
    To read more about "Adrenoleukodystrophy, X-linked"

    Arch Neurol. ; 62(7):1073-80 ; July 2005
    Survey of informed consent for registration of congenital anomalies in Europe
    BMJ ; 331(7509):140-1 ; 16 July 2005
    Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl
    To read more about "Acromegaly"

    Eur J Endocrinol. ; 153(2):195-201 ; August 2005
    cDNA microarray analysis assists in diagnosis of malignant intrarenal pheochromocytoma originally masquerading as a renal cell carcinoma
    To read more about "Pheochromocytoma"

    J Med Genet. ; 42(8):e48 ; August 2005
    New therapeutic & diagnostic approaches
    New therapeutic & diagnostic approaches published on PubMed from July to September 2005
    The European rare diseases therapeutic initiative
    PLoS Med. ; 2(9):e243 ; September 2005
    Prenatal detection of Down's syndrome by rapid aneuploidy testing for chromosomes 13, 18, and 21 by FISH or PCR without a full karyotype: a cytogenetic risk assessment
    To read more about "Trisomy 21"
    To read more about "Trisomy 13"
    To read more about "Trisomy 18"

    Lancet ; 366(9480):123-8 ; 12 July 2005
    Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia
    NEJM ; 353(1):33-45 ; 7 July 2005
    Persistent diastolic dysfunction despite successful long-term octreotide treatment in acromegaly
    To read more about "Acromegaly"

    Eur J Endocrinol. ; 153(2):231-8 ; August 2005
    Quality of life in patients with muscular dystrophy and their next of kin
    Int J Rehabil Res. ; 28(2):103-9 ; June 2005
    Gene Therapy Progress and Prospects: Fetal gene therapy - first proofs of concept - some adverse effects
    Gene Ther. ; Epub ahead of print ; 1 September 2005
    New databases
    New databases published on PubMed between July and September 2005
    Factor XI deficiency database: an interactive web database of mutations, phenotypes, and structural analysis tools.
    Hum Mutat. ; 26(3):192-8 ; September 2005
    International Database of Rare Bleeding Disorders: call for contributors
    An International Database of Rare Bleeding Disorders is being set up to collect information on the distribution of patients affected by these disorders in each region of the world.

    An initiative of a working group of the International Society of Thrombosis and Haemostasis, the database currently contains clinical, genetic and therapeutic information collected over the last 8 years on a large group of severely affected patients scattered in various parts of the world.

    The project leaders want to determine the distribution of each single Rare Bleeding Disorder in the world, and their available treatment. Their final goal is to provide evidence-based guidelines for diagnosis and management of patients affected by Rare Blood Disorders.

    Health professionals working with patients suffering from these disorders are invited to complete a questionnaire on their experience and thus contribute to the international database. Full details can be found on the International Database of Rare Bleeding Disorders website. or by contacting the RBDD project office.

    Genetic testing
    New genetic testing and screening research published on PubMed between July and September 2005
    Newborn Screening — Setting Evidence-Based Policy for Protection
    N Engl J Med. ; 353(9):867-70 ; September 2005
    Universal newborn screening for permanent childhood hearing impairment: an 8-year follow-up of a controlled trial
    Lancet ; 366(9486):660-2 ; 20 - 26 August 2005

    Funding opportunities
    DG SANCO calls for proposals
    Next public health call for end of 2005
    The next call for proposals in the area of public health issues related to rare diseases will be published by DG SANCO at the end of the year. Keep an eye on OrphaNews Europe for full details of the call.
    DG Research calls for proposals
    Final call for life sciences under FP6
    The European Commission's DG Research has released its final call for proposals in the current framework programme under Priority One on 'Life Sciences, Genomics and Biotechnology for Health' with a deadline for 9 November 2005.

    See the July issue of OrphaNews Europe for full details of opportunities for rare diseases research under this call.


    Orphan Drugs
    New designations & authorisations in Europe
    EMEA COMP opinions in July 2005
    At its meeting on 12 –13 July 2005, the EMEA’s Committee for Orphan Medicinal Products (COMP) adopted 17 positive opinions on orphan designation for medicinal products for the following indications:
  • for treatment of soft tissue sarcoma
  • for treatment of tuberculosis
  • for treatment of pulmonary arterial hypertension and chronic thromoembolic pulmonary hypertension
  • for treatment of progressive myoclonic epilepsies
  • for treatment of graft-versus-host-disease
  • for treatment of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency
  • for treatment of shiga-toxin producing bacterial infection
  • for treatment of sickle cell disease
  • for treatment of anal fistula
  • for treatment of dermatofibrosarcoma protuberans
  • for treatment of acute lymphoblastic leukaemia
  • for treatment of mastocytosis
  • for treatment of primary growth hormone insensitivity syndrome
  • for treatment of hyperphenylalaninemia
  • for treatment of 5q spinal muscular atrophy
  • for treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
  • for treatment of acute myeloid leukaemia

  • EMEA COMP opinions in July

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

    New designations & authorisations in Japan
    Japan to start clinical trials with thalidomide for treatment of multiple myeloma
    Japan's Fujimoto Pharmaceutical will shortly begin domestic clinical trials with the formerly banned product, thalidomide, for the new indication of multiple myeloma. The product was given local orphan status for this use earlier this year, as part of a ministry of health, labour and welfare decision to allow development following requests from patient groups. Thalidomide already has orphan designation in Europe and the USA for the same indication.
    SCRIP – World Pharmaceutical News ; 22 August 2005
    PhD thesis on the Orphan Drugs business in Europe
    Daniel Hagn, a student from the Friedrich-Alexander University of Erlangen-Nürnberg, Germany, has written a PhD thesis entitled "Orphan Drugs: a Challenge for the Pharmaceutical Industry in Europe". The thesis has been supported by the EBE (Emerging Biopharmaceutical Enterprises) and copies are now available for sale.

    To order a copy, please fill in this form and send to EBE.


    Ethical, Legal & Social Issues
    Is a specific ethical and legal framework necessary for population-based genetic databases?
    Recent scientific advances and new technological developments, most notably the advent of bio-informatics, have led to the emergence of genetic databases with particular characteristics and structures. Paralleling these developments, there has been a proliferation of ethical and legal texts aimed at the regulation of this new form of database.

    In the current issue of GenEdit, the editorial of the online International Database on the Legal, Social and Ethical Aspects of Human Genetics (HumGen), Anne Cambon-Thomsen, Clémentine Sallée, Emmanuelle Rial-Sebbag and Bartha Maria Knoppers discuss this issue in the context of population-based genetic databases.

    Ethical, legal and social issues in stem cell research and therapy
    The Cambridge Genetics Knowledge Park has produced a stem cells briefing paper. The paper outlines many of the issues surrounding this controversial field and summarises current policy for stem cells in the UK.

    Courses & Educational Initiatives
    Screening Choices: a learning resource for health professionals on antenatal and neo natal screening programmes
    The UK’s National Health Service National Screening Committee has commissioned a project to develop open learning materials for a wide range of healthcare professionals to enable them to help women and their families make informed choices about the antenatal and newborn screening they are offered.

    The materials, available as a CD ROM or via the Internet, are imaginatively presented in an open learning format, highly informative and are generic.

    Units include: Screening in antenatal and newborn care; The parent perspective on screening; Informed choice for everyone: valuing diversity; Understanding genetics; Getting the best from the consultation; Informed choice in antenatal and newborn screening; Understanding and communicating risk


    Press & Publications
    New books
    Smith’s Recognizable Patterns of Human Malformation, 6th edition
    Author: Kenneth Lyons Jones, MD
    Published by Saunders; 2005

    This edition, completely revised and updated, provides guidance on diagnosis, prognosis, plan management, and genetic counselling focusing on the patterns of human defects caused by inborn errors in morphogenesis.

    Handbook of Genome Research: Genomics, Proteomics, Metabolomics, Bioinformatics, Ethical and Legal Issues
    Editor: Christoph W. Sensen
    Published in two volumes by Wiley; June 2005

    Guide to Mutation Detection
    A guide to the theory and practice of mutation analysis

    Editors: Graham R. Taylor, Ian N. Day, Human Genome Organization
    Published by Wiley; February 2005


    What's on where?
    In October
    Jeans for genes day
    Jeans for Genes is a national appeal where everyone across the UK is being asked to throw out the usual dress rules, jump into their jeans and donate money to help children with genetic disorders.

    Date: 7 October 2005
    Venue: Across the UK

    How will EU Pediatric Legislation Stimulate Paediatric Research?
    A European Workshop organised by the European Forum for Good Clinical Practice

    Theme: Narrowing the Gap between the Perspectives of Public Health, Paediatric Research, and Pharmaceutical Industry

    Date: 20 October 2005
    Venue: Brussels, Belgium

    6th EPPOSI Workshop on Partnering for Rare Disease Therapy Development
    This important event will bring together representatives from key stakeholder groups – patients, regulators, charities, the academic and clinical community, industry and health care providers – from across Europe and North America and from the rest of the world.

    The workshop will discuss the issues on the basis of a comparison of best practices and real examples, promote international exchange of information, and look at stumbling blocks and emerging issues. It will also conclude with suggested actions for all stakeholders.

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

    In November
    European Academy of Childhood Disability congress
    Date: 19-22 November 2005
    Venue: Monaco


    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
    Orphanet - All rights reserved