10 December 2008 print
Editorial
EU Policy News
Nat Pol News
ELS News
Orphanet News
New Syndromes
New Genes
Research in Action
Patient Man & Therapy
Orphan Drugs
What's on?
Press & Publications
Subscribe / Unsubscribe
Archives


 
Editorial
 
Rare Disease Task Force moves forward on several fronts in 2008
 


The European Commission’s Rare Disease Task Force gathered in Luxembourg in November to review initiatives undertaken in 2008 and put future actions on the agenda. The Task Force has forks in several fires, and although the recent adoption of the Communication on Rare Diseases took centre stage, many other orders of business were brought up and moved forward.

European Reference Networks
The RDTF working group for European Reference Networks issued a report in July 2008 following a workshop that took place in March 2008. Many aspects of a possible policy to establish European Reference Networks require further clarification. Systematic analysis of the preliminary outcomes of the ten current pilot networks is needed in order to best shape policy. The RDTF scientific secretariat will contribute to this analysis which will be brought to the next RDTF meeting. The existing pilot networks can apply for an operational grant for one additional year. There is still a lot to do before going from a self initiated process to a direct designation of European Reference Networks. It was underlined that the mandate of potential European Reference Networks should be proportionate to a potential budget.

New Orphanet services
The new services developed by Orphanet in 2008 to better serve the RD Community were reviewed. These include the launch in March of a new portal fully accessible to disabled users and more user-friendly than the previous version of the website. In June the information provided for each rare disease was extended to include prevalence data, mode of inheritance, age of onset and causative genes. Orphanet also became cross-referenced with other gene databases such as HGNC, SwissProt, OMIM and Genatlas. Information on expert clinics in Europe was extended to allow sorting by various criteria (type of clinic, paediatric or adult, centre of reference, disease management or genetic counselling). Via a collaborative effort with FP6 network of excellence EuroGentest, the information on medical laboratories was enhanced to encompass information on quality management. Finally, the results of a three-year classification project were unveiled in October. Each rare disease in the Orphanet database is now assigned to one or more classifications depending on the number of clinical manifestations requiring specialised medical expertise. Certain classifications are based on disease mechanism or aetiology. This new feature permits access to all information through any general query, along with the direct visualisation of these classifications.

Indicators
The conclusions of the RDTF working group on indicators in the field of RD were presented, following a meeting in March 2008 and a report published later in the year. The work plan for the coming three year period was presented, as defined by the Joint Action selected for funding this fall which will officially commence in January 2009. The relative merits of aggregated indicators versus disease-specific indicators were discussed. Currently no decision has been taken regarding indicators to be documented. This will be discussed at the next meeting of the working group.

Coding and classification
The working group for coding and classification held a meeting in February 2008 and again on 14 November 2008. The work accomplished by Orphanet in this field was presented. Currently, all published classifications in the field of RD have been collected and added to the Orphanet database. Orphanet has also established a general classification by medical speciality and sub-specialty. All the data have been transferred to the World Health Organisation headquarters to be used as a pilot set of data for the alpha version of the next International Classification of Diseases. Orphanet has established a unique nomenclature of RD which is available to third parties on request. The work plan for the three years to come, as defined by the Joint Action, includes a cross-referencing of Orphanet diseases with ICD10, OMIM, SnoMed-CT and MedDRA. It also includes proposing codes for all recurrent RD in the next edition of the ICD. The proposal will be submitted to WHO by the end of 2009. Classification in the field of RD is the responsibility of the WHO Topic Advisory Group, chaired by Ségolène Aymé. European Commission funding is instrumental in providing the resources to generate proposals to the WHO. The US NIH, along with other equivalent bodies in different regions of the world, will participate in commenting on the proposals and making final decisions.

Outcome of the 2008 call for proposals in the field of Public Health
Six rare disease projects were selected for funding in the field of Public Health in 2008. Not all negotiations are completed yet. The six projects are:
  • Funding for the conference on national plans for RD held in Paris on 18 November
  • A one-year operating grant for Eurordis covering the year 2009
  • A three-year grant for a Joint Action in the Field of RD to provide resources for the RDTF activities mentioned above in the field of indicators, coding and classification, and for publication of OrphaNews Europe - (yey)!
  • Three more pilot networks (chronic hyperventilation syndrome, rare anaemias, and cerebral palsy and related disorders).

  • The next RDTF meeting is scheduled for Thursday 30 April 2009 in Luxembourg.
     


     
    EU Policy News
     
    Second E-Rare call for proposals is now open
     
    As was reported in the last issue of OrphaNews Europe, E-Rare (ERA-Net for research programs on rare diseases) launched its second Transnational Joint Call on 3 December 2008. E-Rare, a network of ten partners – public bodies, ministries and research management organizations – from eight countries, responsible for the development and management of national/regional research programs on rare diseases, is supported by the European Commission under the Sixth Framework Program ERA-Net scheme. The aim of the call is to enable scientists in different countries to build an effective collaboration on a common interdisciplinary research project based on complementarities and sharing of expertise, which takes into account the importance of a translational research approach and the need to strengthen the European Research Area (ERA). Projects shall involve a group of rare diseases or a single rare disease following the European definition (a disease affecting not more than five in 10 000 persons in the European Community). E-Rare has expanded its call to include two more countries - Austria and Greece. Thus, research groups based in Austria, France, Germany, Greece, Israel, Italy, The Netherlands, Portugal, Spain and Turkey and are eligible to receive funding. The deadline for submitting the proposals is the 5 February 2009. Further information can be obtained from the E-rare website .
     


     
    National & International Policy Developments
     
    Bulgaria adopts national plan for rare diseases
     


    On 27 November, the Bulgarian Council of Ministers approved the National Plan for Rare Diseases – genetic disorders, congenital malformations and nonhereditary diseases (2009-2013). This was the last step of a long process that began in November 2006 with the submission of the first draft of the plan by an expert group. Bulgaria’s National Plan for Rare Diseases consists of nine priorities:
  • Collecting epidemiological data for rare diseases in Bulgaria by creation of a national register
  • Improvement of the prevention of genetic rare diseases by enlarging the current screening programmes
  • Improvement of the prevention and diagnostics of genetic rare diseases by introducing new genetic tests, decentralisation of the laboratory activities and easier access to medico-genetic counselling
  • Integrative approach to the prevention, diagnostics, medical treatment and social integration of patients and their families
  • Promotion of the professional qualification of medical specialists in the field of early diagnostics and prevention of rare diseases
  • Feasibility study on the necessity, possibility and criteria for creation of a reference centre for rare diseases of functional type
  • Organising a national campaign for informing society about rare diseases and their prevention
  • Support and collaboration with NGOs and patient associations for rare diseases
  • Collaboration with the other EU members
  • The total budget of the plan is some 22 million Bulgarian leva (€11.3 million). An English-language version of the Bulgarian National Plan for Rare Diseases will be published soon on the ICRDOD (Information Centre for Rare Diseases and Orphan Drugs) website.

     
    New UK rare disease alliance vows to campaign for national plan
     
    A new alliance involving patients, clinicians, government, industry and researchers launched in the UK in early November. Rare Disease UK vows to “campaign for the adoption and implementation of national plans in each of the UK’s home nations” (England, Scotland, Wales and Northern Ireland). The alliance specifies that such plans should “ensure provision of integrated services tailored to the specific needs of those with rare conditions... help make best use of NHS resources and ensure that scarce clinical expertise is deployed to best advance for patient benefit”. Rare Disease UK is a joint initiative between the Genetic Interest Group, (the UK alliance of patient organisations with a membership of over 130 charities which support children, families and individuals affected by genetic disorders) and others in response to the unmet health care needs of families who currently struggle to get access to integrated care and support from the NHS.
     
    Children’s Hospital Boston bequeathed $25 million for rare disease research centre
     
    Touted as the first of its kind, the Manton Center for Orphan Disease Research is being established at Children’s Hospital Boston (USA) via a $25 million grant from the Manton Foundation. Children’s, considered the largest paediatric research institution in the world, welcomes what is one of the largest donations it has ever received, and avowed that the money would go toward opening “a superhighway for discovery”. Children’s Hospital and Harvard Medical School scientists will study and develop new diagnoses and treatments for rare genetic syndromes, immune system diseases, and metabolic and neuromuscular disorders. The gift will also go toward the creation of a Gene Discovery Core, innovation awards for junior faculty, two to three fellowships in orphan disease research, and a visiting scientist programme. The Manton Center for Orphan Disease Research will pair research expertise with clinical resources to develop novel therapies.
     
    Other European news
     
    The Netherlands ranks first in 2008 European health survey
     
    Sweden-based Health Consumer Powerhouse, a leading provider of consumer health information in Europe, has released its 2008 Euro Health Consumer Index (EHCI), an annual report that assesses 31 healthcare systems across Europe. The Netherlands takes the blue ribbon this year - its patient-empowerment policies are cited as a chief reason for its success. The Netherlands has ranked in the top three since the survey began in 2005. To measure the performance of each country, the EHCI has identified 34 indicators organised into six general categories (patient rights and information, e-Health, waiting time for treatment, outcomes, range and reach of services provided, and pharmaceuticals). Denmark and Austria ranked second and third, respectively. The 2008 report stresses that “it is important to recognize the link between medical outcomes and the easiness of access to services and quality information for patients. Good healthcare management and reform is not only a matter of money”. Estonia is singled out as an example of furnishing quality services with “relatively low levels of expenditure”.
    Consult the report

     
    Presentations from 2008 international rare disease conference now available online
     
    ICORD (International Conferences for Rare Diseases and Orphan Drugs) is an international society for individuals active in the fields of rare diseases and/or orphan drugs, including health care, research, academic, industry, patient organisations, regulatory authorities, health authorities, and public policy professionals. The organisation’s fourth conference took place in May 2008. The chosen venue was Washington DC, in honour of the 25th anniversary of the Orphan Drug Act. The speaker presentations from this event are now available online and contain a wealth of perspectives and information on major themes relating to rare disease and orphan drug research and policy from key stakeholders in the field. The next ICORD conference is being held in Rome, Italy, on 23-25 February 2009.
     
    Swedish rare disease meeting reveals need for national plan
     
    The Swedish Association of Rare Disorders held a hearing in mid-November. Amongst the invited speakers were a mother who described living with a child with mucopolysaccharidosis type I; professor of paediatric immunology at the university of Gothenburg Anders Fasth speaking on the necessity of developing centres of excellence in Sweden; EMEA Committee for Orphan Medicines Products chairwoman Kerstin Westermark; Anders Olausson from rare disease information centre and resource facility Ågrenska; various county representatives (in Sweden the counties run the hospitals); and members of the Ministry of Health and Social Affairs. Olivia Wigzell, Director of the Health Care Division at the Ministry of Health and Social Affairs, revealed that the ministry will institute an investigation focusing on the situation of rare disorders in Sweden. All of this momentum was inspired in large part by the work of the EC Rare Disease Task Force and the recent adoption of the Communication on Rare Diseases and Council recommendation. According to one attendee, the overriding conclusion of the meeting was that Sweden needs its own national plan for rare disorders!
     
    Other International News
     
    Hong Kong struggles with cost of rare disease treatment
     
    A recent news article reported that the Samaritan Fund, a charitable source established in 1950 and administered by the country’s Hospital Authority to provide financial assistance to needy patients in meeting expenses not included in hospital maintenance or out-patient consultation fees in public hospitals and clinics, cannot meet the needs of a group of patients with mucopolysaccharidosis. Existing treatment costs up to HK$4 million (€400,500) per year, according to a Hospital Authority spokesperson. According to the news report, more than 20 known patients in Hong Kong suffer from mucopolysaccharidosis, a group of inherited metabolic diseases caused by the absence or malfunctioning of certain enzymes. Cell damage affects patients’ appearance, physical abilities, organs and mental development. Most die before the age of 20. Enzyme replacement therapy became available two years ago for certain forms of the disease and patients and their families have been fighting to have public hospitals provide it since. Using monies from the Samaritan Fund to treat the mucopolysaccharidosis patients would quickly “dry up the fund”. Authorities are examining the issue. Patients’ families don’t care where the money comes from; they simply want access to the new treatment, which they characterise as the “only hope” for some children. The spokesperson of the Patients’ Rights Association is calling on the government to establish a designated fund for patients with very rare diseases. Currently the Samaritan Fund finances several medicinal products, including Etanercept and Infiximab for rheumatoid arthritis, ankylosing spondylitis and juvenile idiopathic arthritis,and Imatinib (i.e. Glivec) for chronic myeloid leukaemia, gastrointestinal stromal tumour and acute lymphoblastic leukaemia.
     
    Iran invests in stem cell research
     
    According to several news sources, Iran is investing some two billion euros in stem cell research, including human embryonic stem cell science. The Iranian Cord Blood Bank states that the sum will be used over a five year period. Currently, researchers are experimenting with treatments for heart disease, multiple sclerosis and other illnesses in both state laboratories and private hospitals in Tehran. The fund will allow such facilities to be developed in other areas of the country. The news reports state that human embryonic stem cell lines were developed in Iran in 2003 under the approval of religious leaders, who define the beginning of life as occurring three months after conception, thus allowing scientists to access human embryonic stem cells left over from fertilization trials. Researchers from the Royan Institute in Tehran are said to be the first in the Middle East and the fifth worldwide to produce human induced pluripotent stem cells, potentially effective for the identification of new (rare) disease models, foetal abnormalities, drug development, and gene therapy.
     


     
    Ethical, Legal & Social Issues
     
    A new website dedicated to patient rights in the EU
     
    The Centre for Biomedical Ethics and Law of the Catholic University of Leuven in Belgium, in collaboration with the European Commission and EuroGentest, has launched a new website devoted to delineating patient rights in the EU. Seeking to encourage transparency and facilitate the exchange of information between researchers both within Europe and further afield, the website offers an outline of the legislative frameworks and key patient rights in each of 25 EU countries. Beside setting out the provisions of the Convention on Human Rights and Biomedicine, the website offers information on a variety of issues for each country, including personal data protection, discrimination, complaints and compensation, and informed consent – matters all relevant to rare disease patients, their families and caregivers. The Preparation of the website was undertaken in the framework of the EuroGentest project. Visit the Patient Rights in the EU website.
     


     
    Orphanet News
     
    Emergenza! Orphanet produces its first Italian language emergency care guidelines
     

    Orphanet has made available online its first Italian language emergency care guidelines for two rare diseases: cutaneous porphyria and classic homocystinuria. Orphanet’s emergency guidelines are expert-authored and peer-reviewed. They are intended to guide health care professionals in emergency situations.
    Consult the Italian language emergency guidelines

     


     
    New Syndromes
     
    A new syndrome associating gingival fibromatosis and dental abnormalities in a consanguineous family
     
    Gingival fibromatosis (GF) is characterised by fibrotic enlargement of the gingiva that can be inherited as an isolated trait or as a component of a syndrome. The authors report one kindred affected by a syndrome characterised by GF associated with dental abnormalities (DA) including generalised thin hypoplastic amelogenesis imperfecta (AI) from a family with multiple consanguineous first-cousin marriages and an autosomal recessive trait of inheritance. Four members demonstrated mild GF in association with DA, including generalised thin hypoplastic AI, intrapulpal calcifications, delay of tooth eruption, and pericoronal radiolucencies involving unerupted teeth. One of the four patients also had intellectual deficit, which was an isolated feature observed in six members. Isolated GF was found in one individual.
    Read the PubMed abstract

     
    J Periodontol ; 1287-1296 ; July 2008
     
    Plexiform angiomyxoid myofibroblastic tumour: a new mesenchymal tumour entity in the stomach
     
    Mesenchymal tumours other than gastrointestinal stromal tumours are rare in the stomach. Plexiform angiomyxoid myofibroblastic tumour is a recently described new entity of a presumably benign mesenchymal gastric tumour. This report presents what is believed to be the third case of this tumour. The tumour is characterised by bland spindle cells in a plexiform pattern, a mucinous extracellular matrix and a network of thin blood vessels. These findings are completely in line with the two previous reported cases. Plexiform angiomyxoid myofibroblastic tumour may present a new mesenchymal tumour entity in the stomach.
    Read the PubMed abstract

     
    J Clin Pathol ; 1136-1137 ; October 2007
     


     
    New Genes
     
    Retinitis pigmentosa: EYS is mutated in autosomal recessive cases
     
    Using a positional cloning approach supported by comparative genomics, the authors have identified a previously unreported gene, EYS, at the RP25 locus on chromosome 6q12 commonly mutated in autosomal recessive retinitis pigmentosa.
    Read the PubMed abstract

     
    To read more about "Retinitis pigmentosa"

     
    Nat Genet ; 1285-1287 ; November 2008
     
    Mammary polyadenomatosis: identification of a gain-of-function mutation of the prolactin receptor
     
    Mammary polyadenomatosis is characterised by multiple fibroadenomas, benign breast tumours which appear most frequently in young women, including at puberty. In a prospective study involving 74 patients and 170 control subjects, the authors identified four patients harbouring a heterozygous single nucleotide polymorphism in the PrlR gene. Hallmarks of constitutive activity were all reversed by a specific PrlR antagonist, which opens potential therapeutic approaches for mammary polyadenomatosis, or any other disease that could be associated with this mutation in future.
    Read the PubMed abstract

     
    To read more about "Mammary polyadenomatosis"

     
    Proc Natl Acad Sci U S A ; 14533-14538 ; 23 September 2008
     


     
    Research in Action
     
    Clinical Research
     
    Wilms tumour: prognostic variables in adult patients
     
    Wilms tumour (nephroblastoma) is a renal cancer that most often occurs in children. The authors collected data on 128 patients with adult Wilms tumour treated between 1973 and 2006. Analyzed factors included age, sex, favourable or unfavourable histopathology, clinical stage, and chemotherapy and radiotherapy received. The outcomes studied included overall survival and disease-specific survival. Adult Wilms tumour has a poorer prognosis than paediatric Wilms tumour. In adults with Wilms tumour, more aggressive patient- and tumour-specific surveillance and adjunctive therapies than those advocated by paediatric National Wilms Tumor Study guidelines may be warranted, especially in patients with an unfavourable histopathology and higher clinical stage.
    Read the PubMed abstract

     
    To read more about "Nephroblastoma"

     
    Can J Surg ; 252-256 ; August 2008
     
    Cornelia de Lange syndrome: epidemiology in Europe
     
    Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. The authors present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (over 8.5 million births in the 1980-2002 period), they found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, foetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. All patients were sporadic.
    Read the PubMed abstract

     
    To read more about "Cornelia de Lange syndrome"

     
    Am J Med Genet ; 51-59 ; 1 January 2008
     
    Trichothiodystrophy: a review of 112 published cases characterises a wide spectrum of clinical manifestations
     
    Trichothiodystrophy (TTD) is a rare, autosomal recessive disease, characterised by brittle, sulfur deficient hair and multisystem abnormalities. A systematic literature review identified 112 patients ranging from 12 weeks to 47 years of age. In addition to hair abnormalities, common features reported were developmental delay/intellectual impairment (86%), short stature (73%), ichthyosis (65%), abnormal characteristics at birth (55%), ocular abnormalities (51%), infections (46%), photosensitivity (42%), maternal pregnancy complications (28%) and defective DNA repair (37%). There was high mortality, with 19 deaths under the age of 10 years (13 infection related). The spectrum of clinical features varied from mild disease with only hair involvement to severe disease with profound developmental defects, recurrent infections and a high mortality at a young age. Abnormal characteristics at birth and pregnancy complications, unrecognised but common features of TTD, suggest a role for DNA repair genes in normal foetal development.
    Read the PubMed abstract

     
    To read more about "Trichothiodystrophy"

     
    J Med Genet ; 609-621 ; October 2008
     
    Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories
     
    The natural history of paroxysmal nocturnal hemoglobinuria (PNH) clinical subcategories (classic PNH and aplastic anemia [AA]/PNH syndrome) is still unknown. The authors retrospectively studied 460 PNH patients diagnosed in 58 French hematologic centres from 1950 to 2005. The median survival time was 22 years. They identified 113 patients with classic PNH, 224 patients with AA-PNH syndrome, and 93 intermediate patients who did not fit within these 2 categories. Although clinical presentation and prognosis factors are different, classic PNH and AA-PNH syndrome present roughly similar outcomes, affected mainly by complications.
    Read the PubMed abstract

     
    To read more about "Paroxysmal nocturnal hemoglobinuria"

     
    Blood ; 3099-3106 ; 15 October 2008
     
    Diagnostic Approaches
     
    Foetal aneuploidy: noninvasive diagnosis by shotgun sequencing DNA from maternal blood
     
    The authors directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This allowed for measuring the over- and under-representation of chromosomes from an aneuploid foetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of foetal aneuploidy. Using this method, the authors successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week.
    Read the PubMed abstract

     
    Proc Natl Acad Sci U S A ; 16266-162671 ; 21 October 2008
     


     
    Patient Management and Therapy
     
    Pulmonary arterial hypertension: addition of sildenafil to long-term intravenous epoprostenol therapy
     
    Pulmonary arterial hypertension is a rare condition characterised by elevated pulmonary arterial resistance leading to right heart failure. Oral sildenafil and intravenous epoprostenol have independently been shown to be effective in patients with the disease. To investigate the effect of adding oral sildenafil to long-term intravenous epoprostenol in patients with pulmonary arterial hypertension, the authors designed a 16-week, double-blind, placebo-controlled, parallel-group study with 267 patients with pulmonary arterial hypertension (idiopathic, associated anorexigen use or connective tissue disease, or corrected congenital heart disease) who were receiving long-term intravenous epoprostenol therapy. Patients were randomly assigned to receive placebo or sildenafil. The study found that in some patients with pulmonary arterial hypertension, the addition of sildenafil to long-term intravenous epoprostenol therapy improves exercise capacity, hemodynamic measurements, time to clinical worsening, and quality of life, but not Borg dyspnea score. Increased rates of headache and dyspepsia occurred with the addition of sildenafil.
    Read the PubMed abstract

     
    To read more about "Pulmonary arterial hypertension"

     
    Ann Intern Med ; 521-530 ; 21 October 2008
     
    Fabry disease: a tale of two enzymes
     
    Fabry disease is an X-linked inborn error of glycosphingolipid metabolism due to a deficient activity of alpha-galactosidase A, a lysosomal homodimeric enzyme. In Europe, two recombinant enzymes have been authorised as treatments: agalsidase alpha (Replagal; Shire) and agalsidase beta (Fabrazyme; Genzyme). The first of these is indicated at 0.2 mg/kg every two weeks; while the second treatment is administered at 1.0 mg/kg every two weeks. The annual cost for the two treatments is almost identical for the dosages indicated, even though agalsidase-alpha costs some five times more per milligram of protein than agalsidase beta. In 2007, Vedder and colleagues demonstrated in an open randomised clinical trial that the two treatments administered at equal doses had a similar effect on the cardiac, renal and cerebral parameters monitored. In July of this year, the same team presented the results of a new study that compared 31 patients treated indiscriminately with either agalsidase alpha or agalsidase beta administered at 0.2 mg/kg versus 21 patients receiving 1.0 mg/kg of agalsidase beta every two weeks. The authors demonstrated that of all the patients who developed antibodies directed against the two substitute enzymes, those taking the higher concentration (agalsidase beta) had a reduction of GL-3 in the urine.

    Mehta and colleagues, in a letter recently published in Molecular Genetics and Metabolism, firmly contest these results. The chief protestation concerns the grouping together of the patients treated with a low concentration of each enzyme to compare with the group treated with the higher dosage of agalsidase beta. The authors assert that, as is documented in the literature, the two enzymes are not strictly identical and cannot be treated as is they were. Vedder et al in response cite different studies that demonstrate that the two enzymes are functionally equivalent. While they concede that a larger study is needed to confirm these results, they defend their hypothesis that the presence of antibodies influences the dosage of enzymes to be administered.

     
    To read more about "Fabry disease"

     


     
    Orphan Drugs
     
    One approval, one refusal and one withdrawal from the CHMP this month
     
    The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion on initial marketing authorisation for Nplate (romiplostim), from Amgen Europe B.V., for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura. Nplate is the 51st orphan medicine to receive a positive opinion by the CHMP. EMEA review began on 21 November 2007 with an active review time of 203 days.

    Following the re-examination of the negative opinion adopted on 24th July 2008, the CHMP confirmed its previous position and adopted a final negative opinion by consensus for Sovrima (idebenone), from Santhera Pharmaceuticals GmbH, a designated orphan medicine intended to be used for treatment of Friedreich’s Ataxia. Read more about this opinion

    The European Medicines Agency (EMEA) has been formally notified by Novagali Pharma S.A. of its decision to withdraw its application for an initial marketing authorisation for Vekacia (ciclosporin) 0.05% eye drops. Vekacia, a designated orphan medicine, was expected to be used for the treatment of vernal keratoconjunctivitis. Read more about this decision.

     
    FDA approves Banzel for seizures associated with Lennox-Gastaut syndrome
     
    In the USA, the Food and Drug Administration has approved Banzel (rufinamide) for use as an adjunctive treatment for seizures associated with Lennox-Gastaut syndrome. Lennox-Gastaut syndrome is a severe form of epilepsy that usually begins before 4 years of age. Banzel, granted orphan drug designation by the FDA, is manufactured by Eisai Medical Research Inc.
     


     
    What's on Where?
     
    The Multiple Faces of Lamins in Aging and Disease
     
    Date: 6-9 January 2009
    Venue: Vienna, Austria

    This workshop will bring together scientists from diverse research areas, working on lamins and laminopathies – with a particular focus on newly emerging aspects in lamin function (e.g. stem cell, signaling). It is also intended to foster interdisciplinary interactions between basic scientists and clinical researchers as well as patient organizations.
    For further details

     
    EuroGentest Workshop: Validation of Diagnostic Tests in Clinical Molecular Genetics
     
    Date: 8-9 January 2009
    Venue: Prague, Czech Republic

    Genetic tests must be validated before diagnostic use to ensure that they perform according to the laboratory requirements, and test validation is a formal requirement of many accreditation standards including ISO 15189. This workshop will examine the validation requirements of ISO 15189 and address practical ways of meeting them in the laboratory.
    For further details

     
    IBC Conference: Ushering in the New Era of Orphan Disease R&D, Clinical & Business Strategies
     
    Date: 5-6 February 2009
    Venue: Bethesda MD, USA

    Conference organiser IBC’s Inaugural Orphan Diseases conference will aim to deliver valuable information in a strategically organized and refined format for both industry and non-profit organizations. Regulatory Perspectives from the FDA & EMEA will provide global advice for successful commercialization; Scientists from Siena Biotech, NIH & Novartis will help understand common orphan disease mechanisms; and the National Organization for Rare Disorders (NORD) will describe effective mentoring strategies for new orphan disease companies to ensure success.
    For further details

     
    International Conference on Rare Diseases and Orphan Drugs (ICORD 2009)
     
    Date: 23-25 February 2009
    Venue: Rome, Italy

    More detailed information will follow soon.
    For further details

     
    Second International Rare Disease Day
     
    Date: 28 February 2009
    Venue: Everywhere!

    Check with the official website in coming weeks to locate activities in your region.
    For further details

     
    BPSU 2009 Conference
     
    Date: 3 March 2009
    Venue: London, England

    The British Paediatric Surveillance Unit (BPSU) has put together a programme that reviews the contribution the BPSU has made to the understanding and control of uncommon childhood conditions, it’s impact on public health policy and it’s development of partnerships.
    For further details

     
    3rd International Congress on Rare Pulmonary Diseases and Orphan Drugs
     
    Date: 20-21 March 2009
    Venue: Milan, Italy

    This conference will consider new issues in rare pulmonary diseases and examine aspects of individual disorders.
    For further details

     
    Drug Information Agency 21st Annual EuroMeeting
     
    Date: 23-25 March 2009
    Venue: Berlin, Germany

    Alongside the traditional areas of drug development, regulation and patient safety, topics featured include information technology, the importance of appreciating the patient perspective, and the connection between drugs and medical devices (combination products).
    For further details

     
    Molecular Mechanisms of Neurodegeneration
     
    Date: 8-10 May 2009
    Venue: Milan, Italy

    Addressing the most important issues involved in protein toxicity in neurons, providing participants with updated information that could be useful to researchers in the field of neurodegenerative disorders.
    For further details

     
    7th World Congress on Melanoma
     
    Date: 12-16 May 2009
    Venue: Vienna, Austria

    A joint meeting with the 5th Congress of the European Association of Dermato-Oncology. Clinicians and researchers will focus on the state of the art in prevention, recognition, and treatment of cutaneous neoplasms covering melanoma and non melanoma skin cancer as well as lymphomas and rare skin tumours. Deadline for submission of abstracts: 31 January, 2009.
    For further details

     
    8th Balkan Meeting on Human Genetics
     
    Date: 14-17 May 2009
    Venue: Cavtat, Croatia

    "Rare diseases – public policy, research, diagnosis and management" is one of the topics featured in this conference. Deadline to submit an abstract is 20 January 2009.
    For further details

     
    12th International Congress on Neuronal Ceroid Lipofuscinoses
     
    Date: 3-6 June 2009
    Venue: Hamburg, Germany

    The aim of this meeting is to facilitate and speed up exchange between expert scientists and physicians, but also to confront young researchers with the challenges of the largest group of degenerative brain diseases in young people. Deadline for submission of abstracts: 28 February, 2009.
    For further details

     
    Fourth International Conference on Birth Defects and Disabilities in the Developing World
     
    Date: 4-7 October 2009
    Venue: New Delhi, India

    The theme of the Fourth International Conference is "Translating Research into Cost-effective Services for the Care and Prevention of Birth Defects, Preterm Birth and Consequent Disabilities". Deadline for submission of abstracts: 15 April, 2009.
    For further details

     


     
    Press & Publications
     
    Noonan Syndrome and Related Disorders
     
    Author: M. Zenker, Ed.
    Publisher: S. Karger AG (Switzerland)
    ISBN 978-3-8055-8653-5

    Noonan syndrome is a genetic disorder characterised by abnormal development of various parts of the body, including unusual facial characteristics, short stature, bleeding problems, heart defects, skeletal malformations and eye abnormalities. The cause is a mutation in one of two genes responsible for making a specific type of protein that is crucial for the formation of several types of tissue during development. This new book provides an in-depth discussion on the disorders of the Ras-MAPK pathway (Noonan-, cardio-facio-cutaneous-, Costello-, and LEOPARD syndromes). The articles treat both the clinical and molecular data exhaustively and give the reader a timely update and outline of these related disorders. This book is aimed for clinical geneticists, paediatricians, paediatric cardiologists and paediatric endocrinologists, as well as human molecular geneticists and other basic researchers working on the RAS pathway.

     
    Challenges to obtaining optimal rare disease therapy
     
    An article that was published in the Proceedings of the Western Pharmacology Society, entitled Optimal therapy for rare disorders and genetic diseases: ethical and political challenges compares the definitions of rarity between the USA, Australia and the European Union and explores how variations in understanding terminology can impact scientific progress. Differences between the significance genetic predisposition is accorded pose similar obstacles. The author lists impediments blocking the process of treatment development for rare diseases that science alone cannot overcome. Most of these are well known to anyone working in the field. The author concludes that health technology assessment must encompass the values of the individual and the society and not be limited to an exclusively utilitarian perspective.
    Consult the PubMed abstract

     
    An ode to early failure (and to the critical path initiative of the FDA)
     
    An article published recently in the Journal of Medicine and Philosophy considers how the US Food and Drug Administration (FDA) can best assist in the translation of medicinal products from bench to bedside. High R&D costs are forcing companies to make short-sighted business plans that often exclude the potentially risky breakthrough products that target rare diseases. The FDA’s critical path initiative, a programme designed to speed the development of drugs to market, is heralded as an instrument that aids companies navigate the rocky road leading to successful product development. To be more efficient, this initiative needs development tools that can better predict a drug development cycle and bring down research costs by allowing industry to identify product failures earlier. With an estimated 50% of drugs under development failing in Phase 3, the author considers the implications of helping companies fail earlier: a 10% improvement in predicting failure before clinical trials could save $100 million (€77 million) in development costs; shifting 5% of clinical failures from Phase 3 to Phase 1 would reduce out of pocket costs by $15–$20 million (€11-€15 million); and shifting one-fourth of failures from Phase 2 to Phase 1 would save $12–$21 million (€9-€16 million). To be most effective the critical path initiative and government regulatory agencies must achieve a complementary (versus competitive) working relationship. The author calls for continued and enhanced cooperation between regulators and industry, patient groups and legislators, and the FDA and European Medicines Agency (EMEA), in order to make the 21st century the “Biomedical Century”.
    Consult the PubMed abstract

     
    Now is the time for all good researchers to come to the aid of their patients
     
    In a recent article published in the review Molecular Genetics and Metabolism, the authors describe Clinical research for rare disease: Opportunities, challenges, and solutions. Molecular genetics have characterised the cause of many rare diseases and provide unprecedented opportunities for identifying patients, determining phenotypes, and devising treatments to prevent, stabilise, or improve each disease. Rare disease research poses particular challenges to investigators, particularly in terms of designing clinical studies, accessing adequate funding, developing treatments, and training of clinical scientists. For trainees interested in finding a treatment for a rare disease, a commitment to longitudinal care of patients provides a base for the characterisation of phenotype and natural history, a stimulus for innovation, a target population for research and helps fund training and research. The authors describe how the scientific methodology, financial resources, and logistics of clinical research for rare diseases have changed dramatically in the past two decades, resulting both in increased understanding of the pathophysiology of these disorders and in benefits to patients and their families. Indeed, in their conclusion, the authors state that “although challenges specific to studying rare diseases remain, the opportunities for contributing to exciting scientific discoveries, forging successful research careers, and, most importantly, improving the lives of people with rare diseases have never been better”. Hooray!
    Consult the PubMed abstract

     


     
    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: Ségolène Aymé
    Editor: Louise Taylor
    Contact Us
    Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Armelle Regnault, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
    For more information on the Rare Diseases Task Force
    Orphanet - All rights reserved