20 November 2006 print
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The 7th EPPOSI Workshop in Madrid: Toward more Collaborative Efforts to Position Rare Diseases on the Healthcare Agenda
Two days of active discussion between more than 120 patients representatives, professionals from Academia and Industry from both sides of the Atlantic took place in Madrid (Spain) on 26-27 October. This was the 7th EPPOSI Workshop dedicated to partnering in the field of rare diseases. EPPOSI stands for European Platform of Patients Organisations, Science and Industry. Each year, a workshop is organised in a different European capital to provide a platform for a debate on ways to improve developments in therapeutic solutions as well as their accessibility in Europe. Key players in the US are also invited to contribute to the discussion. This year the workshop focussed on the question of positioning rare diseases on the healthcare agenda.

Read the full Editorial on EPPOSI and News of the 2nd ICORD...


Task Force Update
Forthcoming RDTF meetings in 2006 & 2007

The 6th meeting of the Rare Diseases Task Force will be held on 14 December 2006 at the European Commission in Luxembourg, from 9:00 to 17:00.


Spotlight on...
…The North American approach to Biochemical Genetic Testing Quality

The challenges of Europe’s biochemical genetic testing are currently handled by the network of excellence EuroGentest. But what of rare disease genetic testing challenges currently encountered on the other side of the “Big Pond” ?

Spotlight recently talked to Steve Groft, Director of the Office of Rare Diseases (ORD) at the US National Institute for Health (NIH), who explained the results of a key working meeting organized last month in Atlanta by the ORD/NIH, attended by major decision-makers from the North American genetic testing (GT) community on “Quality, Access, and Sustainability of Biochemical Genetic Testing”. The talks are the latest in a series of events dealing with this hot topic including a Conference in Rockville 2005 and Workshop in 2004, focussing on biochemical genetic testing as a major area of laboratory testing for genetic diseases.

Orphanet attended this otherwise exclusively North American event. Participants were welcomed by Drs. Joe Boone, CDC and Steve Groft, NIH ORD. Plenary presentations included an overview and outlook of biochemical genetic testing by Dr. Mike Watson, American College of Medical Genetics (ACMG); results of a recent Society for Inherited Metabolic Disorders (SIMD) laboratory survey by Drs. Carol Greene and Bruce Barshop; European efforts on information resources for genetic testing by Dr. Valérie Thibaudeau for Orphanet and Eurogentest; updates on the Collaboration, Education, and Test Translation (CETT) Program for Rare Genetic Diseases by Dr. Giovanna Spinella, ORD, NIH; and examples of coordination between biochemical and molecular genetic testing in improving diagnosis and patient management by Drs. David Ledbetter, Art Beaudet, and Andy Faucett. Participants then formed 3 break-out groups: Access and Sustainability, Quality Assurance, and Information Resources, to address issues more specifically in each of the focus areas.

The presentations and discussions revealed a surprising amount of common ground between European and US genetic testing policy. Europe’s experience with the recent Eurogentest project for public access, up-to-date information on genetic testing that is harmonising European standards provides an interesting parallel with the longer-established US CLIA certification model. The US regulation is firmly backing GT practice and a recent Progress Report from US Congress has addressed the development of diagnostic tests, stressing the need to meet the CLIA (Clinical Laboratory Improvement Amendments).

SPOTLIGHT Interview with Steve Groft, Office of Rare Diseases (ORD) at the US National Institute for Health (NIH)

Orphanews: What were the chief aims of the Atlanta “Quality” talks ?
SG: Our objectives can essentially be summed up in two words: Access & Availability. The US CETT Programme (Collaboration, Education & Test Translation Program)is designed to improve access to biogenetic and molecular diagnostic testing and “essential” prenatal testing, whilst the public availability of the genes programme is all-important. It is designed to improve understanding of the CLIA and testing quality standards including collection of the genotype and clinical information.

Read the full SPOTLIGHT interview…

Call for reader feedback… Do you have any ideas or questions for the US Office of Rare Diseases ?
If so, Steve Groft and his colleagues would like to hear from you.


EU Policy News
European Regulation for Paediatric Medication Quality & Safety is adopted
The 25 European States have unanimously adopted new EU regulations imposing specific tests on companies dealing with the effects of medication on children, to improve the efficacy and safety of these paediatric products.

In its approval of all amendments voted by the European Parliament, the Council of the European Union last month adopted the regulation relating to paediatric medication, which aims to: accelerate developments in paediatric medication, guarantee that medication used in paediatrics be subject to quality research and, where necessary, check that medication be submitted to appropriate authorisation.

This will be achieved by the effects of forthcoming legislation which can be summed up as follows:

  • Creation of an inventory of specific needs for paediatric medicinal products

  • Creation of a Paediatric Committee, replacing the Paediatric Expert Group (PEG) at the EMEA. All MS will be represented by one expert in the Committee. Six additional members will be nominated, of which 3 will be patient representatives (parents or family members) and 3 health professionals

  • The market exclusivity will be extended by 2 years for children’s orphan drugs (an increased total duration of 12 years, up from 10)

  • A process is to be implemented ensuring children are not subjected to unnecessary clinical studies

  • Information available on the use of paediatric medication must be improved in total conformity with EU legislation on clinical trials.

  • The regulation will come into enforcement on 1 January 2007.

    Background reading

    Paediatric Drugs Regulation final draft (10 Oct 2006)

    Read the EC/EMEA document on priorities for implementation in new paediatric drugs legislation

    EMEA Reflection Paper: Formulations of choice for the Paediatric Population

    Guideline on conduct of pharmacovigilance for medicines used by the paediatric population
    The EU has selected six European networks of expertise for rare diseases
    The results of its Call for proposals intended to finance proposals for European reference centre networks for healthcare provision concerning a rare disease or a group of rare diseases from 2007 over a three-year period. DG Sanco has selected six networks of Centres of reference for rare diseases or a group of rare diseases, spanning six EU countries. They are currently in the negociation phase and will serve as pilot projects for reference networks of Centres of expertise:

    -European Centres of Expertise Network for Cushing Syndrome (Dr Susan Webb, University of San Pau, Barcelona)
    -European Centres of Expertise Network for porphyria (Prof. Jean-Charles Deybach, Paris)
    -European Centres of Expertise Network alpha-1 antitrypsin deficit (Prof. Jan Stolk, Leiden)
    -European Centres of Expertise Network for dysmorphic syndromes (Prof. Jill Clayton-Smith, Manchester)
    -European Centres of Expertise Network for cystic fibrosis (Prof. Thomas Wagner, Frankfurt)
    -European Centres of Expertise Network for hemorragic syndromes (Prof. Flora Payvandi, Milan).

    DG Enterprise
    The Orphan Medicinal Products annex to guideline update is online
    In preparation for the coming enlargement, the annex to Guideline on the format and content of applications for designation as OMPs and on the transfer of designations from one sponsor to another has been updated on the EC’s Enterprise/Pharmaceuticals website (Revision: 24 October 2006).
    Developing European guidelines for ethical children's clinical trials
    A draft document on Ethical Considerations for Clinical Trials Performed in Children Recommendations of the Ad Hoc Group for the development of implementing guidelines for Directive 2001/20/EC relating to good clinical practice in the conduct of clinical trials on medicinal products for human use has been released by the EC's DG Enterprise and Industry.

    This draft presents recommendations on various ethical aspects of clinical trials performed in children, intending to contribute to their protection as the subject of clinical trials as well as facilitate a harmonised approach to clinical trials across the EU Member States, considering that the approval of clinical trials (including ethical approval) is primarily a national competence, thereby facilitating the conduct of clinical trials in the EU.

    You may send in your comments for this coming draft document using this template to mailto:entr-pharmaceuticals@ec.europa.eu by 31 January 2007 at the latest.


    National & International Policy Developments
    Other European news
    News from Denmark
    The Ministry of Social Affairs has decided to fund the establishment of a Centre for Rett syndrome. The centre will be housed by the Kennedy Institute, Glostrup, Denmark. The centre will build up a multidisciplinary team to assist Denmark’s patients (approx. 100) and families with matters concerning the coordination of various issues such as social needs, medical care, physiotherapy etc. Activities will include counselling of newly diagnosed cases about all aspects of the disease, as well as research and knowledge promotion.
    News from France
    Two leading rare disease researchers, both women, have been awarded top prizes by the French National Medical Research Institute (INSERM). They are Ketty Schwartz and Marina Cavazzana-Calvo.

    Currently Emeritus Director of Research at France’s National Centre for Scientific Research (CNRS), Ketty Schwartz was one of the first women in France to take on the job of Director of a medical research unit, 1981-1985, at both the Lariboisičre and the Pitié-Salpétričre Hospitals in Paris. Twice Vice-president of INSERM’s Board of Directors and co-founder of its Institute of Myology, she has both medically and politically had a lasting impact on the rare disease landscape, largely due to her pioneering work with the French Association for Muscular Dystrophy (the AFM, responsible for the national Telethon held each year in France since 1987). She is also renowned for her contribution to molecular biology research into the cardiac and skeletal muscles.

    In the early 80’s, Ketty Schwartz helped transform the state of isolation and neglect in which patients with rare diseases found themselves at the time, partly by setting up discussions between groups of patients with their families on the one hand, and key research and healthcare players on the other. Since then, she continues to play a defining role in the AFM’s promotion of RD research to the public and media and works closely with a patients’ consultative group for important decision-making in biomedical research and healthcare at INSERM.

    Marina Cavazzana-Calvo, who has been awarded the Clinical and Therapeutic Research prize, is Director of the Biotherapy Department at Necker Children’s Hospital in Paris, where she has been working for nearly 20 years, and is also Head of an INSERM unit there. Her chief contribution has been research into the definition of a gene therapy protocol for children with severe combined X-linked immune deficiency.

    Born in Venice, Marina Cavazzana-Calvo studied medicine in Padua but a period of work on transplantation early on in her career at the St Louis Hospital in Paris led her to put down roots in the French capital. It was there that a decisive meeting with Prof. Alain Fischer (now a close colleague at INSERM) meant she became highly involved in the prevention of graft rejection by the injection of monoclonal anti-bodies. Her collaboration with Fischer continued and they concentrated their activities on the problem of immune deficiency suffered by “bubble babies” X-chromosome-linked including research into the mono-gene DICS-X, a short-term lethal disease. Armed with a dedicated research team, they concentrated on the gamma (c) gene and the transfer of deficient cells by gene therapy. This therapy for children involved the removal of lymphocyte T precursors and NK cells as well as stem cells. Despite a major setback with some of the first children’s cases treated, the conclusive gene therapy protocol established by Marina Cavazzana-Calvo proved to be highly successful.


    Research in Action
    A European Scientific Prize for Researchers
    The NRJ Foundation-French Institute is once again this year offering an award of 100,000€ for a team of researchers from France or another European country with an international reputation in the field of neuro-science, to enable the team to expand its activities. The theme for 2007 will be “Pathology of the Memory”.
    Deadline for applications: 18 December 2006 How to apply (in French only)

    EU project focus
    The new PHGEN (Public Health Genomics European Network) website is launched
    The PHGEN Network, which has recently launched its new website, sets out to examine issues and priorities in public health genomics. With EU funding running from January 2006 through December 2008, the PHGEN will serve the European Commission as an ‘early detection unit’ for horizon scanning, fact finding, and monitoring of the integration of genome-based knowledge into public health at large. It includes three active Working Groups on Definitions, Genetic Exceptionalism and Issues & Priorities as well as National Task Forces which have already held meetings this year in Italy and Turkey. Further meetings are lined up this month in Portugal, Germany and Belgium.

    For more details about PHGEN activities: Contact Dr Peter Schroeder

    New diseases & syndromes
    Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract

    A new autosomal recessive white matter disorder, hypomyelination and congenital cataract, is characterized by hypomyelination of the central and peripheral nervous system, progressive neurological impairment and congenital cataract. Mutations were identified in five affected families, resulting in a deficiency of hyccin, a newly identified 521-amino acid membrane protein. The study highlights the essential role of hyccin in central and peripheral myelination.

    Nature Genetics; 38 : 1111-1113; Oct 2006

    A Novel Mutation in FGFR3 Causes Camptodactyly, Tall Stature, and Hearing Loss (CATSHL) Syndrome

    A new syndrome characterized by camptodactyly, tall stature, scoliosis and hearing loss (CATSHL syndrome) has been described in approximately thirty members of a seven-generation family. It is caused by a heterozygous missense mutation of the FGFR3 gene, coding an inhibitor of chondrocyte terminal differentiation. Seven syndromes characterised by an endochondral bone growth reduction and caused by activating mutations of FGFR3 have been described. On the contrary, the mutation observed in the CATSHL syndrome is responsible of a partial loss-of-function of FGFR3. So far, disruptions of the FGFR3 signaling pathway could induce bone abnormalities in humans, either by inhibiting or promoting the endochondral bone formation.

    AJHG; 79(5) : 935-9412; Nov 2006

    New genes
    New rare disease genes published on PubMed
    Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking
    To read more about "Craniolenticulosutural dysplasia"

    Nature Genetics ; 38 : 1192-1197 ; Oct 2006

    Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase
    Nature Genetics ; 38(10): 1184-1191 ; Oct 2006
    Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles
    Nature Genetics ; E-pub ahead of print ; 8 Oct 2006
    The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia
    To read more about "Anonychia, congenital"

    AJHG ; E-pub ahead of print ; Nov 2006

    Nature Genetics ; E-pub ahead of print ; 15 Oct 2006
    Lamin B1 duplications cause autosomal dominant leukodystrophy
    Nature Genetics ; 38 : 1114-1123 ; Oct 2006
    An updated mutation spectrum in an Australian series of Peutz-Jeghers Syndrome patients provides further evidence for only one gene locus
    To read more about "Peutz-Jeghers syndrome"

    Clinical Genetics ; 70 : 409 ; Nov 2006
    Mutation in the Auxiliary Calcium-Channel Subunit CACNA2D4 Causes Autosomal Recessive Cone Dystrophy
    To read more about "Cone rod dystrophy"

    AJHG ; 79 : 973-977 ; Nov 2006
    Mutations in the Tight-Junction Gene Claudin 19 (CLDN19) Are Associated with Renal Magnesium Wasting, Renal Failure, and Severe Ocular Involvement
    To read more about "Renal hypomagnesemia - hypercalciuria - nephrocalcinosis"

    AJHG ; 79 : 949-957 ; Nov 2006
    Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype
    To read more about "Lamellar ichthyosis"

    Journal of Investigative Dermatology ; E-Pub ahead of print ; 14 Sept 2006

    Human Molecular Genetics ; 15 : 3083-3097 ; 1 Nov 2006

    New fundamental research
    Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. American researchers show that TDP-43 is the major disease protein in both neurodegenerative disorders.
    To read more about "Amyotrophic lateral sclerosis"
    To read more about "Frontotemporal dementia"

    Science ; 314 : 130-133 ; 6 Oct 2006
    New clinical research

    Speech and language delay are early manifestations of juvenile-onset Huntington disease

    Yoon G., Kramer J., Zanko A., Guzijan M., Lin S., Foster-Barber A., Boxer AL.

    The neuro-cognitive features of juvenile-onset Huntington disease (HD) are not well understood. Yoon et al. present three patients with onset of HD symptoms before age 10 years in whom speech delay was the first symptom.

    Neurology ; 67(7) : 1265-1267 ; 10 Oct 2006

    Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial

    Given that no effective therapeutic options for patients with unresectable imatinib-resistant gastrointestinal stromal tumour are available, an American team carried out a randomised, double-blind, placebo-controlled, multi-centre, international trial to assess tolerability and anticancer efficacy of sunitinib, a multitargeted tyrosine kinase inhibitor, in patients with advanced gastrointestinal stromal tumour who were resistant to or intolerant of previous treatment with imatinib, with encouraging results.

    In view of the fact that EMEA has received new clinical data from Pfizer concerning the stable but non-progressive state of metastatic renal cancer patients treated with Sutent, it has just recommended that a conditional marketing authorisation become a standard one for Sutent in the two indications referred to above. It also recommends that the Sutent indication be extended to advanced and/or metastatic renal cancer treatment initally.

    EMEA Press Release; 16-18 Oct 2006

    The Lancet; 368(9544):1329-38; 14 Oct 2006

    Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion

    Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. A team investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31- clone in patients with this disorder on a group of 148 patients. 112 patients were found to have a reduced need for transfusions and 99 patients no longer required transfusions, regardless of the karyotype complexity. The response to lenalidomide was rapid and overall results were positive. This treatment has been authorised in the US since 28 December 2005 for the treatment of patients suffering from a myelodysplasic syndrome associated with a 5q deletion.

    NEJM; 355 : 1456-1465; 5 Oct 2006

    Multiple system atrophy could be distinguished from idiopathic Parkinson's disease by the arginine growth hormone stimulation test

    Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). The aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central system modulating GH release in MSA.

    Annals of Neurology ; E-pub ahead of print ; 6 Sept 2006

    Chronic health conditions in adult survivors of childhood cancer

    Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. Oeffinger et al. determined the incidence and severity of chronic health conditions in adult survivors. Using a retrospective cohort study tracking the health of adults having received a childhood cancer diagnosis between 1970 & 1986, the results were compared with those of siblings. The frequencies of chronic conditions were calculated in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. It was concluded that survivors of childhood cancer have a high rate of illness due to chronic health conditions: cancers (breast cancer, colorectal cancer, melanoma and non-melanomateous cutaneous cancer), coronary diseases, late cardiomyopathies linked to anthracycline, pulmonary fibrosis and endocrinopathies (insufficient premature gonadic, thyroid disease, osteoporosis, disorders of the hypothalamic and hypophysary function). A survivor presents a 3.3 risk increase of suffering from a chronic pathology compared with a member of the survivor’s siblings, and an 8.2 risk increase of developing a disease that could jeopardise the survivor’s life prognosis.

    NEJM; 355 : 1572-1582; 12 Oct 2006

    IN THE NEWS...

    A new NIH-led US Consortium for clinical research is launched

    The USA’s NIH (National Institute of Health) has launched a new national consortium for clinical research. The operation includes 12 research centres for health, including the Mayo Clinic College of Medicine as well as the universities of California, Pennsylvania and Yale which will develop the clinical discipline. Between now and 2012 a further 60 institutes will join forces with the consortium.

    Creation of a Franco-Italian “Associated European Laboratory”

    Last month saw the creation of an “Associated European Laboratory” between France’s National Medical Research Institute (INSERM) and a biomedical research laboratory from an Italian scientific institution. The AEL is “Adhesion Molecules in Skin Repair and Tumorigenesis” with INSERM Unit 634 / Nice Sophia Antipolis University and the Istituto Dermopatico dell'Immacolata - Istituto di Ricovero e Cura a Carattera Scientifico (IDI-IRCCS) Dermatological Institute in Rome, for Rare Skin diseases and cell adhesion mechanisms.

    Huntington’s disease : new test improves screening of drug treatment

    A new test using cultured cells provides an effective way to screen drugs against Huntington's disease and demonstrates that two compounds - memantine and riluzole - are most effective in keeping cells alive in conditions which emulate the disorder, report US researchers from UT Southwestern Medical Center.

    Read more

    Read Pubmed

    New Recommendations for Stem Cell Research in Germany

    Despite new findings made in international stem cell research in recent years, Germany has been unable to develop its scientific contribution in this field due to current restrictive legal framework conditions. Due to the key date regulation and the penalties established in the Stem Cell Act of 2002, German researchers are denied access to new cell lines and, to a large extent, prevented from working on international projects. In view of the situation, the DFG (Deutsche Forschungsgemeinschaft), Germany’s central, self-governing research funding organisation that promotes research at universities and other publicly financed research institutions in Germany, has produced new recommendations for stem cell research, including proposals for modifying the legislation.

    Read more

    Read the full recommendations (German only – English due to appear shortly)

    New Clinical Trials
    A mono-centre clinical trial in Finland in the treatment of Glioblastoma or Anaplastic Astrocytoma

    A Phase II/III international multi-centre clinical trial in France in the treatment of Vernal Keranoconjunctivitis

    Click here to register your interest in participating in a clinical trial visit

    Orphan drug research
    Hunter Syndrome: EMEA backs long-term treatment by Elaprase
    Despite fears over the costs involved in the long-term treatment of Hunter Syndrome (mucopolysaccharidose type II), (see UK Times article). EMEA has recently given Elaprase (idursulfatase) a positive opinion for the drug’s marketing. The Agency’s recommendation for marketing authorisation for Elaprase will be given under exceptional circumstances since the disease is so rare that the Shire Human Genetics Therapies company responsible for developing and testing Elaprase, is considered unable reasonably to provide comprehensive data on the safety or efficacy of the drug. EMEA has therefore decided to review the medicinal product on an annual basis.

    Elaprase, which has been authorised in the US since August 2006, is the 33rd European orphan medicinal product to obtain a positive CHMP opinion.

    EMEA Press Release (16-18 October 2006)

    Read more about Mucopolysaccharidosis type 2


    Orphanet News
    Orphanet Journal of Rare Diseases
    The Orphanet Journal of Rare Diseases, in collaboration with Biomed Central, publishes free access articles on rare diseases and orphan drugs indexed by Pubmed. It has added the following 10 new articles to its online collection since the beginning of October 2006:

    New online articles:

    Multiple endocrine neoplasia type 2

    Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40

    Congenital pulmonary lymphangiectasia

    Klinefelter syndrome and other sex chromosomal aneuploidies

    Primary sclerosing cholangitis

    Retinitis pigmentosa

    Foetal and neonatal alloimmune thrombocytopaenia

    Multiple endocrine neoplasia type 1

    Tuberous sclerosis

    The Challenges of Proteus Syndrome: diagnosis and management

    Forty-five articles have been published since the Journal's creation on 1 March this year, of which 42 are Review articles, 1 is a Case study, 1 is a Research article and 1 is an Editorial. Nine of these published articles have already been given the Highly Accessedť label which means in practice that each article has received at least 500 hits during the fortnight immediately following its publication.

    Click here for a complete definition of the Highly Accessed label.

    Submit your article now!


    The following research project leader would like to hear from interested potential collaborators:

    A team from Ben-Gurion University in Israel is interested in collaborating with Arab countries or European countries with Arab populations on the following research project:

    Identification of the molecular basis of rare disease in in-bred consanguineous populations mainly of Bedouin or Arab ancestry. Molecular identification of the genes in chromosomal breakpoints in phenotypes stemming from de-novo balanced chromosomal translocations and inversions.

    Contact Project Leader Ohad Birk

    Read more at the website of the Laboratory of Human Molecular Genetics, Ben-Gurion University, Israel

    Read an example of the team's work this year in a New York Times' weekly science section cover story about research and genetic testing for rare genetic disorders in Bedouin communities living in Israel's Negev region.

    Is your project feeling lonely?...

    Use OrphaNews Europe's PartnerSearch if you are looking for partners for your research project, your patients organization, 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.


    Orphan Drugs
    Severe myoclonic epilepsy in new-borns: Diacomit now set for authorisation in Europe

    Following a positive opinion from EMEA, the anti-epileptic drug, Diacomit (stiripentol) should soon obtain conditional marketing authorisation for use in the treatment of severe myoclonic epilepsy in new-borns, associated with clobazam and valproate. The Biocodex laboratories, which market the medication, are committed to supplying the additional data presenting the efficacy of stiripentol associated with maximum doses of clobazam and valproate, and comparing the bio-availability of Diacomit in sachets and capsules.

    The EMEA will reevaluate Diacomit each year to confirm that the benefit-risk remains positive. Diacomit is the 32nd orphan drug to obtain a positive opinion for its marketing in Europe. It has retained its positive opinion in France since 2002 for the same indication in the frame of a compassionate use cohort.

    EMEA Press release; (16-18 Oct 2006)

    Glivec receives indication extensions in Europe and the US but Novartis withdraws a marketing authorisation extension

    Glivec (imatinib mesylate) recently received a positive opinion from the EMEA's Committee for Medicinal Products for Human Use (CHMP) following its meeting held on 16-18 October, for a marketing authorisation extension regarding:

    - the treatment of myelodysplasic syndromes and myeloproliferative diseases; - the treatment of hypereosinophilic syndrome and chronic eosinophilic leukaemia in adults.

    Parallel to this, Glivec was simultaneously given the green light by the FDA for five supplementary indications all corresponding with rare forms of cancer including a restrained therapeutic choice, dermato-fibrosarcoma, hypereosinophilic syndrome, severe lymphoblatic refractory leukaemia with Philadelphia chromosome as well as certain myeloproliferative syndromes. Glivec is now authorised by the USA in the treatment of seven pathologies of which five are rare haematological diseases and two are types of solid tumours.

    Conversely, Novartis announced its decision on 23 October to withdraw its EMEA application to extend the marketing authorisation for Glivec. In February this year, the company submitted an application for the extension of marketing authorisation to include treatment of aggressive systemic mastocytosis in adults. Imatinib mesylate had been designated as an OMP for the treatment of mastocytosis on 26 August 2005.

    The company's official reason for withdrawal was the consideration of the Agency's Committee for Medicinal Products for Human Use (CHMP) that the limited data given did not permit it to conclude on a positive benefit-risk balance of the drug's use in aggressive systemic mastocytosis.

    Read EMEA press release (marketing authorisation extension); 16-18 Oct 2006

    Read EMEA press release (Novartis withdrawal); 23 Oct 2006

    Maturity of judgement in decision-making for predictive testing for non- treatable adult-onset neurogenetic conditions: a case against predictive testing of minors

    International guidelines developed to minimize harm from predictive testing for adult-onset, non-treatable neurogenetic conditions such as Huntington disease (HD) state that such testing should not be available to minors. Some authors have proposed that predictive testing for these conditions should be available to minors at the request of parents and/or of younger adolescents themselves. They highlight the lack of empirical evidence that predictive testing of minors causes harm and suggest that refusing to test minors may be detrimental. This study focuses on the context of predictive test requests by adolescents younger than 18 years, and presents arguments and evidence that the risk of potential harm from testing such young people is sufficiently high to justify continued caution in this area. An Australian study based on a model of psychosocial maturity found that the 3 factors involved in maturity of judgement in decision making - responsibility, temperance and perspective - continue to develop into late adolescence. In addition, evidence that the prefrontal areas of the brain, which are involved in executive functions such as decision-making, are not fully developed until early adulthood. Combined with evidence of adverse long-term effects, from research with adults who have undergone predictive testing, these findings constitute grounds for retaining a minimum age of 18 years for predictive testing for non-treatable conditions. Continued maturity assessment research should help to reach a conclusion on this subject.

    Clinical Genetics; 70(5) : 396-401; Nov 2006


    Ethical, Legal & Social Issues
    The Emergence of an Ethical Duty to Disclose Genetic Research Results: International Perspectives

    Bartha Maria Knoppers, Yann Joly, Jacques Simard & Francine Durocher

    European Journal of Human Genetics, 2006, 14, 1170-1178, ISSN: 1018-4813

    This article discusses the emergence of international ethics guidelines on the disclosure of global and certain individual genetic research results, in the light of developing pharmacogenomics and increasing translational genetic, post-genomic research. This incorporates a survey of literature and ethical guidelines using selective keywords, followed by a qualitative analysis of data. The results led to the singling out of certain countries or policies representative of certain positions, and, on the international level, to conclusions indicating an ethical duty to return individual genetic research results subject to the existence of proof or validity, significance and benefit. This leads to many questions regarding who should be responsible for disclosing such results and when, and to whom should the results be disclosed and how? Finally, the authors question whether this ethical imperative will become a legally recognized duty as well.
    Read more

    Social issues
    New report on disability policy by Finland's Government

    In Finland, the principle of non-discrimination of disabled people is enshrined in the Constitution. However, its policy in favour of disabled people for the past ten years, aiming at a society for all, has not reached its objective in spite of the development of actions encouraging the integration of disabled people and total integration in daily life.

    Read the Finnish Ministry for Social Affairs & Health Summary

    Abstracts resulting from the Conference: Disability and Classifications: from Concepts to action held 25-26 October, 2006 in La Marsa, Tunisia

    Read the abstracts (texts in French & English)


    News from the Patients Associations
    Eurordis update
    Trans-European patient mobility: EURORDIS prepares a position paper for the new EC public consultation
    Patient mobility across the European borders is a crucial issue for many rare disease patients suffering from insufficient medical treatment or services in their own Member State. EURORDIS is preparing a position paper to coincide with a new public consultation by the European Commission (Read the Communication from the Commission) on health services and patient mobility. The move was launched in September this year, following widespread fears about the uneven quality of healthcare currently experienced by many patients between the EU countries.

    Healthcare in the EU is technically the responsibility of all Member States, but recent European Court of Justice rulings have ruled that EU citizens may use health facilities in other MS and benefit from reimbursement by their own national health system in cases where their own country of origin is unable to provide those facilities. The draft Directive formerly known as the Bolkestein Directive, updated and adopted by MEPs on 15 November this year, on Services in the Internal Market excluded health services in Spring 2006, however the European Court of Justice rulings have proved that EU law includes them, much to the relief of the patients concerned. These events have led to the decision to hold a public consultation designed to put forward a framework proposal in 2007. Commissioner Kyprianou has called it an opportunity to shape the future of healthcare in Europe, adding that whilst Community law effectively provides patients with the right to cross-border healthcare, it is obvious that Europe now needs a clear, practical framework to reconcile greater individual choice with the sustainability of health systems overall.

    Main aspects to be dealt with by the consultation will include mobility of both patients and professionals, services and how they should be delivered from- and to- different EU countries. The resulting legislation is expected to clarify all legal aspects of trans-frontier health services and cooperation between the national health systems. The consultation particularly hopes to receive ideas on: legal aspects (safety, care, compensation, etc.); possibility of European action to support Member States (eg. Networks of Centres of Expertise); tools necessary for the implementation of these issues and finally, assessment of current impact of trans-frontier healthcare on national health systems (NB patient mobility now represents 1% of overall public health expenditure).

    The EURORDIS position paper representing rare disease patients across Europe will be completed in time for the public consultation deadline of 31 January 2007. The association has formed a drafting group including representatives from 7 EU countries, many with first-hand experience of the cross-border health services problem. OrphaNews readers with a personal experience in seeking provision of healthcare services across European borders that they are willing to share can contact EURORDIS . The paper, which will integrate the comments received by EURORDIS, will be finalised in December before its submission to the Commission.

    Alternatively, to respond to the consultation individually, to send an email to the Commission by 31 January 2007 at the latest. All contributions submitted to the Commission will be published, unless otherwise indicated.

    Some background reading:

    Patient Mobility & Healthcare Development overview

    Developing a Community Framework for Safe, High Quality and Efficient Health Services

    Research Assistant in Empirical Bioethics, Alden March Bioethics Institute, New York, USA

    The Alden March Bioethics Institute, a multi-institutional bioethics research organization based at the Albany Medical College in New York, seeks a Research Assistant. The successful candidate will work on both highly complex empirical bioethics projects currently funded by the NIH and on the development of nascent research programs with teams of investigators. This position will put the successful candidate into what amounts to a bioethics lab, ideal for the junior scholar or scholar-in-training looking to build a career in bioethics research. More details

    Statistician, Catalan Institute of Oncology, Dept. of Epidemiology, Barcelona, Spain

    The "Group of Nutrition, Environment and Cancer" is seeking a Statistician for the Department of Epidemiology in Barcelona, Spain. It requires a candidate with an MSc degree in Biostatistics to join the project "European Prospective Investigation into Cancer and Nutrition" (EPIC) in the research Spanish co-ordination team in Barcelona.

    More details

    Ophthalmologist, National Center of Reference for Inherited Sensory Diseases, University Hospital of Montpellier, France

    The University hospital of Montpellier is seeking an ophthalmologist for a full-time position in Montpellier's National Centre of Reference for Inherited Sensory Diseases. The center has 15 years’ experience in inherited retinal dystrophies during which it has provided clinical and molecular diagnosis for more than 900 families, in partnership with several local centres for the rehabilitation of deaf/blind patients.

    More details


    Courses & Educational Initiatives
    Orphan Europe Academy training courses for healthcare professionals working with rare diseases

    The Orphan Europe Academy organises training and educational activities for healthcare professionals involved in the research, diagnosis and treatment of patients affected by rare disorders. It offers specific courses focused on well defined problems in the fields of diagnosis and treatment. These courses bring together healthcare professionals, increase awareness in this medical field, and stimulate international networking.

    Two of the courses the Academy has scheduled to date:

    Paediatric Movement Disorders 31 May-2 June 2007 Sant Joan de Deu Hospital, Barcelona, Spain

    1st European Adult Metabolic Course (In partnership with the Institute of Neurology, London) 30 January – 3 February 2008 Institute of Neurology, London

    Registration & full programme


    Press & Publications
    New books

    Respiratory Genetics

    Authors: Edwin Silverman, Steven Shapiro, David Lomas & Scott Weiss
    Published by Hodder Education, ISBN-10: 0340814322, ISBN-13: 978034081432130, Sept. 2006.

    New Clinical Genetics

    Authors: Andrew Read & Dian Donnai
    This text book is chiefly aimed at medical students, taking a new approach to clinical genetics based on real-life cases of people with rare genetic disorders.
    Scion Publishing Limited, ISBN 1904842313, Nov 2006
    350 pages, approx. 42 €

    Retina e-dition, 4th edition

    Authors: Stephen J. Ryan, David R. Hinton, Andrew P. Schachat, Charles P. Wilkinson
    Published by Mosby, ISBN 0323040918, Sept. 2005

    New Articles

    FDA Regulation of Stem-Cell-based Therapies

    Authors: Dina Gould Halme & David A. Kessler
    New England Journal of Medicine, 355;16, 19 Oct 2006

    Read NEJM

    Orphan drug designation and pharmacogenomics: options and opportunities

    The rapid increase in characterization and understanding of the human genome has had a major impact on the development of therapies for rare diseases. The "inborn errors of metabolism", which are generally rare diseases, are beginning to realize new therapies based on an understanding of disease processes, as well as acquired genetic errors, at the genetic level. Since its inception, the Office of Orphan Products Development has witnessed many of the successes and also the failures of pharmacogenomics as it relates to rare diseases. This approach, from a regulatory standpoint, often calls into question even basic assumptions about disease classification. Phenotypically homogeneous diseases are more frequently becoming 'subsetted' on the basis of genomics; conversely, overlap of therapeutic mechanisms of action is increasingly seen across seemingly diverse diseases. With the recent sequencing completion of the human genome, as well as the increasing ease of DNA sequencing, the pharmacogenetic approach to treatment will be expected to play an increasingly important role in developing new therapies for rare and common diseases alike.

    Office of Orphan Products Development

    BioDrugs; 20(2) : 71-79; 2006

    Protecting the Health of the Public – Institute of Medicine Recommendations on Drug Safety

    Authors: Bruce M. Psaty & Sheila P. Burke
    New England Journal of Medicine, Vol. 355;1753-1755, 26 Oct 2006

    Read NEJM

    Hemostasis and Thrombosis: Basic Principles and Clinical Practice

    Edited by: Robert W. Colman, Victor J. Marder, Alexander W. Clowes, James N. George, and Samuel Z. Goldhaber. New England Journal of Medicine, Vol. 355; 1839-1840, 26 Oct 2006

    Read NEJM

    Genetic Disorders in the Arab World

    Authors: Lihadh Al-Gazali, Hanan Hamamy, Shaikha Al-Arrayad
    British Medical Journal, Vol. 333, 21 October 2006

    Read the BMJ

    New reports
    Consent & Confidentiality in Genetic Practice (Guidance on genetic testing and sharing genetic information) by the Royal College of Physicians, Royal College of Pathologists & British Society for Human Genetics, UK

    A Report of the Joint Committee on Medical Genetics, ISBN 1 86016 278 9, April 2006

    The Human Tissue Act 2004 : an assessment of the Act and its implications for the specialties of clinical and laboratory genetics

    The Human Tissue Act 2004), which regulates the removal, storage and use of human organs and tissue and makes legal consent possible in specific circumstances, has been law since 1 September 2006. Edited by the Joint Committee on Medical Genetics of the British Society for Human Genetics, this report takes up the main points of this Law and analyses the practical consequences that it will have in genetic laboratories as well as in clinical practice.

    How to purchase this report


    What's on where?
    In January
    In November
    European Cystic Fibrosis Awareness Day (ECFAD: 21 November 2006

    The aim of this CF day is to raise public awareness and political interest on the European level for all people confronted with CF. The average life expectancy for CF sufferers with access to appropriate CF care is now 40 years, however in some parts of Europe, patients die before reaching adolescence. Awareness campaign activities will be taking place all over Europe from 17-26 November. ECFAD is organised by the European CF Society, the WHO and CF Worldwide.

    Read more

    Rare Disease Congress: "Childhood - Rare Diseases - Orphan Drugs"

    23-24 November 2006
    Athens, Greece

    Workshop on Biomarkers and their Potential in Human Biomonitoring and Environmental Health Surveillance

    29 November 2006
    Room M6, Jean Monnet Building (JMO), Luxembourg

    International Conference on Hemolytic Uremic Syndrome (HUS)

    November 30- December 1, 2006
    Ranica (Bergamo), Italy
    Read Programme

    In December
    20th Telethon in France

    8-9 December 2006
    Details (French only)

    Rare Diseases March

    9 December 2006
    Details (French only)

    Italian National Folic Acid Network Workshop

    15 December 2006
    Istituto Superiore di Sanitŕ, Rome, Italy
    Details (Italian only)

    In 2007

    Governing Genomics Conference: interdisciplinary perspectives on the regulation of the biosciences

    25-27 January 2006
    Reed Hall, University of Exeter, UK

    2nd EPPOSI Workshop on “Value of Innovation”

    22-23 January 2007
    Dublin, Ireland


    Genomic Disorders 2007

    21-23 March 2007
    Wellcome Trust Conference Centre, Hinxton, Cambridgeshire, UK

    Fifth International Conference of the European Chromosome 11q Network

    22-25 March 2007
    Hohenwart-Pforzheim, Germany


    1st European Working Group on Rett Syndrome

    19-20 April 2007
    University of Insubria, Busto Arsizio (VA), Italy

    1st Mediterranean Summit: Description of Rare Diseases and Treatment Highlights - Mapping Rare Diseases and their Management in the Mediterranean

    20-23 April 2007
    Contact Nasia Tsaroucha for more details


    First Prader-Willi Syndrome Scientific Workshop and Conference, Romania

    21-24 June 2007
    Cluj-Napoca, Romania


    ESSOP 2007 Annual Meeting Health Systems and Child Health: Lessons from cross-country comparisons

    European Society for Social Paediatrics and Child Health
    13-14 September 2007
    Trieste Stazione Marittima, Italy
    Contact for more details


    European Conference for Rare Diseases - ECRD 2007

    27-28 November 2007
    Lisbon, Portugal
    More details in next month's OrphaNews


    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 Ségolčne Aymé
    Editor: Kathy Beuzard-Edwards
    Contact Us
    Editorial Board: Ségolčne Aymé, Aurélie Bedin, Catherine Berens, Helen Dolk, Anders Fasth, Edmund Jessop, Jordi Llinares-Garcia, Jérôme Parisse-Brassens, 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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