21 November 2007 print
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Commission Communication on Rare Diseases now available for consultation
A Public Consultation for a future Communication on European Action in the Field of Rare Diseases, entitled Rare Diseases: Europe's Challenges, drafted by the European Commission in close collaboration with the Rare Diseases Task Force, is now available, and will ultimately serve as a guide for shaping priorities and informing decisions for rare disease strategies in the present and future European Member State health policy programmes. This Communication will hopefully be followed by a recommendation of the Council.

Though not legally binding for Member States, Communications and Recommendations nonetheless have a major political influence. They are intended to help formulate and implement coordinated national objectives and strategies in areas, including Public Health, that are the responsibility of individual Member States and not subject to EU-level binding acts such as Regulations and Directives.

The Public Consultation for Rare Diseases: Europe's Challenges contains thirteen questions that focus on coding and classification for rare diseases, testing and population screening for rare diseases, electronic informational tools, orphan drug accessibility, social and educational services, registries, databases and biobanks, partnerships with industry and NGOs, and national/regional action plans. These items are intended to help meet critical objectives, including improving knowledge and the identification of rare diseases, accelerating research and development, improving diagnostics, and coordinating both national and EU-level policies and initiatives, such as national rare disease plans. Responses to the consultation do not need to focus exclusively on the thirteen questions. The consultation document is presently available in English language and will be accompanied by translations in 21 EU languages. The full Communication will be available in these 21 languages on the European Commission Health & Consumer Protection Directorate-General website between 6 and 13 December 2007. Responses and comments to the Communication should be sent to the European Commission by 14 February 2008.

OrphaNews Europe strongly encourages all interested stakeholders, including researchers, patient group representatives, pharmaceutical companies, and especially Member State policy makers responsible for developing national health priorities, to carefully review and respond to this Public Consultation in order to ensure that all EU countries are equally empowered to furnish their rare disease patients with equitable health care treatments and services. After incorporating the suggestions received from the Public Consultation and impact assessment of the EU services, the Communication will be presented to the European Parliament, the Council of Ministers, the Economic and Social Committee, and the Committee of Regions. It is expected that the Parliament and the Council of Ministers will issue Recommendations on how to implement the suggested actions presented in this Communication.


Spotlight on...
Spain's major new scientific cooperative for rare disease research

The Centre for Biomedical Network Research on Rare Diseases (CIBERER) is a virtual institution composed of 45 basic, clinical and epidemiological research groups distributed throughout 27 different Spanish academic, public research, and university hospital institutions in nine different cities. Formally established in November 2006, over 450 investigators are involved in the effort. The cooperative network aims to establish itself as an international centre of knowledge, transforming the fruits of its research into clinical practice by strongly encouraging collaboration between basic and clinical research. The activities of CIBERER are organised into seven distinct scientific areas that share the common goal of investigating the rare diseases that fall within their respective domains. These areas are: mitochondrial disorders, hereditary metabolic diseases, endocrinal diseases, neurogenetics, congenital and developmental defects, clinical and epidemiology genetics, and genetic instability and cancer predisposition.

CIBERER is led by Scientific Director Dr. Francesc Palau, a specialist in paediatric medicine and medical genetics, working as a senior investigator at the Institute of Biomedicine, Spanish Council of Scientific Research (CSIC) in Valencia. In a recent interview with Redes de Investigacion en Medicamentos, the Spanish pharmaceutical industry publication that featured an in-depth feature article on CIBERER in their July 2007 issue, Dr. Palau described the overall mission of the rare disease scientific network: stimulating and supporting rare disease scientific research, particularly the fields of genetic, molecular, biochemical and cellular investigation.

CIBERER has five principal directives:
  • Improving the resources available for researching rare diseases and rare disease treatments
  • Promoting the integration between basic and clinical biomedical research groups, in order to unite the laboratory with the clinical setting
  • Developing cooperative investigational projects that permit the exploration of new scientific hypotheses and technological developments
  • Demonstrating the value of rare disease research
  • Establishing collaborative efforts with pharmaceutical and biotechnology firms
  • To achieve these objectives, the CIBERER groups purposely work in intramural settings. Two-thirds of the researchers belong to universities and research institutions, and the rest work from various hospital-based settings, such as genetic clinics. This diversity fosters one of the principal aims of the project: facilitating collaboration between basic and clinical research to create a continuum from the laboratory to the clinical setting, both in terms of diagnostics and treatments. The CIBERER research groups are located all over Spain: Barcelona and Madrid each have 16 research groups and the others are distributed throughout the country: six in Valencia, two in Seville, and one in each of the following five cities: Malaga, Santiago de Compostela, Murcia, La Laguna (Tenerife) and Zaragoza.

    CIBERER has its antecedents in the Cooperative Thematic Research networks that were developed in Spain between 2003 and 2006. Of the 69 centres or groups that made up this effort, 11 concerned rare diseases, including the Clinical and Molecular Genetic Centres Network (RECGEN) and the Research Institute for Genetic-Based Rare Diseases (INERGEN). CIBERER also collaborates with the Rare Disease Research Institute of the Instituto de Salud Carlos III (ISCIII), an intramural institute created several years ago that has since been oriented toward epidemiology. CIBERER will work on a project with this group concerning rare disease registries. Determining rare disease prevalence in Spain, particularly for rare genetic-based disorders, is a necessary procedure that can be achieved by creating registries. This task requires close collaboration with hospital and clinical genetic services, as well as patient organisations and other sources. With an estimated 80% of rare diseases having a genetic basis, improving diagnostics in this area is vital. Implementing new technologies that allow automatic large-scale genetic analysis, and ultimately reduce the time to results is also important, and are on the "to do" list amongst CIBERER's many other goals.

    CIBERER, created by the ISCIII as a public network structure, is an independent legal entity. Funded by ISCIII, CIBERER has a budget of 6.2 million euros for its first year. This sum is scheduled to increase annually, with a 10% augmentation for the coming year. This monetary commitment reflects the involvement on the part of the government and the general public toward addressing the problem of rare diseases.

    CIBERER structures its working scientific areas to maximise cooperative, multidisciplinary research. This intramural approach allows investigators to consider different approaches, exploring new hypotheses and technological developments. Several mechanisms are set up to foster this collaboration. Symposia, in which research between different strategic programmes is shared, are one such device. These seven distinct research areas each has a variety of projects, often working in collaboration with national and international researchers. Each has its own set of working groups and an ambitious agenda of projects geared to forwarding understanding of rare diseases and possible preventive or treatment strategies:

    The mitochondrial disorders are multisystemic pathologies that can affect several diverse organs. The scientific coordinator for this area, Pr. Julio Montoya, emphasises the particular significance of mitochondrial disorders to rare diseases. Their multi-systemic character, coupled with an etiology not completely understood, makes working in this field particularly challenging. Yet it is hoped that advances in understanding rare mitochondrial diseases will have repercussions that extend to more common disorders and other branches of medicine. The role of genetics in these illnesses is key and studies employing transmitochondrial cybrids are expected to help decipher the mystery these illnesses present.

    The area of hereditary metabolic disorders consists of 12 research groups coordinated by Pr. Magdalena Ugarte. Investigating the molecular foundation of this group of diseases in order to find new therapies is the principal global work objective. Studying defects in cerebral creatine, congenital glycosylation anomalies, cellular physiopathology and new genetic and pharmacological therapy approaches occupies the scientists working in this sector.

    The endocrinal disease segment of CIBERER has five research groups that are investigating endocrinal anomalies in rare diseases. Scientific coordinator Dr. Pascual Sanz elaborates in Redes de Investigacion en Medicamento that furthering the understanding of the molecular foundation of genetic endocrinal disorders figures amongst the primary objectives, as well as investigating the epidemiology of genetic or acquired rare endocrinal disorders. The groups in this area have specific and varied objectives, and include the study of the molecular bases of various disorders, such as Lafora-type myoclonic progressive epilepsy, Osler Weber Rendu disease, or those caused by mutations in the human pancreatic gluco-kinase or AMP kinase gene. Analysing the genes involved in sex differentiation, congenital hyperthyroidism, and the morbidity-mortality of Cushing syndrome and acromegalia are other topics under investigation. This group is also responsible for the coordination, development and launch of the European Registry on Cushing syndrome (ERCUSYN) and the Spanish Acromegalia registry.

    The neurogenetics group, coordinated by Dr. Montserrat Baiget, has the global objective of furthering understanding of the causes and mechanisms of rare neurogenetic pathologies in order to ultimately develop new diagnostics and therapies. Five research groups throughout the country are working on a variety of projects. Major disorders addressed include muscular dystrophies, spinal muscular atrophy, Charcot-Marie-Tooth disease, Friedreich ataxia, retinal dystrophies and genetic deafness.

    The congenital and developmental defects research sector of CIBERER is coordinated by Dr. Carmen Ayuso. These disorders affect as many as 5% of newborns, and lead to elevated morbidity and mortality rates, especially in developing countries. This research sector consists of five working groups, one of which is devoted to epidemiology. Projects include studying the embryology of the vertebrae and disorders related to bone development, analysing genetically modified mice models of diseases such as Wiskott-Aldrich syndrome and other chromosomal pathologies. Other projects concern hereditary ocular pathologies (with participation in Spanish project EsRetNet and European FP6 project Evi Genoret), non-invasive prenatal diagnostics, the identification of chromosomal and genetic causes of infertility, and the study of congenital malformations such as bone dysplasias.

    The clinical and epidemiology genetics work package is coordinated by Dr. Guillermo Antinolo, and is focused on better harnessing the numerous advances in the field of genetics that are allowing for deeper understanding of many rare diseases and how they are transmitted. Prenatal diagnosis and reproductive genetics is one topic of study, along with work being conducted to analyse the molecular basis of several rare disorders, including Hirschsprung disease, and hereditary cancers. Population genetics is being investigated, and the work area has multi-disciplinary research teams consisting of biologists, physicians, psychologists, statisticians, and laboratory workers collaborating to characterise rare diseases and accomplish related tasks.

    Genetic instability and cancer predisposition is the seventh research area of CIBERER. The six working groups, coordinated by Pr. Jordi Suralles, are investigating mutations leading to genomic instability. Diseases such as Fanconi Anaemia, which has 13 genes implicated to date, and hereditary cancer are the focus of research for this working group. One research group is focusing on bioinformatics, while another is working on gene therapy for skin disorders such as epidermolisis bullosa.

    At the first annual meeting of CIBERER, taking place in November, scientists from the seven main disciplines of research will be able to share the fruits of their efforts.

    Though less than a year old, the CIBERER research groups are remarkably active, producing research and publishing their findings. To date, almost 20 publications written by or in collaboration with various CIBERER research groups can be found on PubMed and 35 publications and meeting reports can be found in the ISI Thompson Web of Science. This research includes studies in fundamental and clinical science and can be found in some of the leading international scientific and medical journals.

    CIBERER stands as a model of innovation and commitment in the field of rare disease research, whose efforts seem poised to benefit rare disease patients and their families not only in Spain, but all over Europe and the world.

    EU Policy News
    Rare diseases included in new European health strategy
    On 23 October, the European Commission adopted a new Health Strategy. Together for Health: A Strategic Approach for the EU 2008-2013 builds on existing work to continue a strategic framework enveloping major health issues and policies throughout the European Union. The Strategy is designed to define clear objectives to inform health priorities at the European level, and implement mechanisms to achieve these objectives, in conjunction with individual Member States. The European Commission Staff Working Document accompanying the White Paper identifies rare diseases as a priority. Rare diseases also figure amongst the health priorities outlined in the Health Strategy White Paper. Amongst the actions appearing within the paper's first objective (Fostering good health in an ageing Europe) is a call for A Communication on European Action in the Field of Rare Diseases. This action is already being fulfilled, as OrphaNews Europe's current Editorial describes.
    Networks of Excellence seek permanence
    CORDIS, the European Commission's Research and Development Information Service, recently reported that a group of some 60 Networks of Excellence (NoEs), representing over 13 000 researchers, has issued an opinion paper calling on the European Commission to implement actions that would provide them with long-term sustainability and ultimately help them become permanent legal structures. Most NoEs were first created under the EU's Sixth Framework Programme in order to strengthen scientific and technological excellence in specific areas by integrating research capacities. Over 170 NoEs have been created to date. However, reduced funding for NoEs (only 17 NoEs were funded in the first call of FP7 versus 101 in FP6, and continued support for existing NoEs has not been announced) and difficulties in establishing permanent legal structures has prompted the drafting of the opinion paper. Four specific actions have been identified that would ensure more security for NoEs. These include an EC reconfirmation of its commitment to NoEs as tools that provide structure to European research and reduce fragmentation; the possibility of additional funding via a competitive process; a comprehensive review of the impact of NoEs as well as an analysis of long-term sustainability, perhaps leading to the creation of best practice guidelines; and the development of a "network of networks" that would result in new interdisciplinary areas of research. Amongst NoEs supporting the campaign for sustainability that are involved in rare disease research are EuroGentest, Treat-NMD, Teddy, and Clinigene.
    DG Sanco rare disease events page updated
    The DG Sanco Public Health Rare Diseases events page has been updated to include upcoming rare disease conference and symposium events around the globe.

    National & International Policy Developments
    Other European news
    Genetic test communication under the microscope in the UK
    The NHS National Genetics Education and Development Centre has issued a report detailing the experiences and preferences of patients receiving genetic information from health care professionals. The report enquires as to what, when, and from whom patients prefer to receive genetic information and includes a range of patients or family members presenting with many conditions, including Gorlin syndrome, Marfan syndrome and other autosomal dominant conditions; autosomal recessive disorders such as Gaucher disease, retinitis pigmentosa; X-linked conditions (Fragile X, ectodermal dysplasia); chromosomal conditions (translocation involving chromosome 22, cri du chat syndrome, Trisomy 21); and a multifactorial condition (autism). Amongst the findings: healthcare professionals need greater awareness of genetic conditions, patients prefer a range of information providers, patients want information to be adapted to fit individual needs, they want information to be provided in a non-judgemental manner, and several respondents expressed a desire for a holistic approach to care. With many conditions affecting multiple organs and body parts, patients and families are required to see various specialists, leading to a feeling of fragmentation in their care with no one person overseeing the condition as a whole. Other points raised included a need to simplify genetic terms and concepts - words such as risk and mutant can be frightening for patients. The lack of availability of certain genetic information, the impact of genetic information on the rest of the family, the utility of patient support groups and internet resources, and the expert patient phenomenon in which, particularly for very rare disorders, the patient or caretaker feels that they know more about their condition than their healthcare professional were other points raised in the report.
    Results of genetic test validity and utility evaluation released
    The British charitable institution, Foundation for Genomics and Public Health (PHG), has published the results of an expert workshop that sought to measure the validity and clinical utility of genetic tests - including testing for rare diseases. The workshop took place in June 2006 in the United Kingdom under the auspices of the Organisation for Economic Cooperation and Development (OECD). Representatives from 17 OECD member countries attended the event and contributed their experiences. The objectives included sharing international perspectives of genetic test evaluation practices. A presentation on Genetic testing for rare diseases in the United Kingdom brought up points relevant to all countries: It must be considered whether diagnosis would be possible without molecular testing. Would such testing remove the need for other expensive or invasive testing? Would such testing impact possible treatment options? Would the result of such testing affect the lifestyle choices of the patient or family significantly? For pre-symptomatic screening, would a positive test result accurately predict the future of the disease and alter management? Would a negative test result be definitive? Would molecular diagnosis reduce the need for testing in the rest of the family? Would it provide a means of pre-natal or carrier detection? The patient perspective was presented during the workshop and neatly summed up what patients seek when undergoing genetic testing - Available, Comprehensible, Compassionate, and Equitable services. Amongst the recommendations emerging from the workshop to move toward meeting these needs was the call for an agreed framework for genetic test evaluation that incorporates a formal international network approach. The full workshop summary will be available on the PHG Foundation website.
    Other International News
    The Nobel Prize for knock-out mouse researchers
    The achievements of three scientists working independently to create the revolutionary knock-out mouse model that permits researchers to introduce specific gene modifications via embryonic stem cells that can determine the role a certain gene plays in development, physiology and pathology have garnered the most noble of accolades: the 2007 Nobel Prize in physiology or medicine. It is believed that the efforts of Mario Capecchi (University of Utah), Martin Evans (University of Cardiff), and Oliver Smithies (University of North Carolina) in developing the handy knock-out mouse will contribute extensively to revealing the role of genetic influences in human disease, including the thousands of rare disorders known to have a genetic basis.
    Taiwan broadcasts rare disease concerns to the general public
    Taiwan has a robust rare disease lobby, the Taiwan Foundation for Rare Disorders (TFRD). Established in 1998 by two parents of children with rare disorders, the group has blossomed into an active force, advocating for the rights of rare disease patients. Perhaps their crowning achievement is the campaign they undertook for the adoption of the Rare Disease and Orphan Drug Act, which came into being in Taiwan in 2000. This 36-article legislation includes decrees regarding the acquisition of orphan drugs, R&D, manufacturing orphan drugs, diagnosis and treatment of rare diseases, prevention, acknowledgement of rare diseases, cooperation with international rare disease organisations, and the subsidised supply of specific pharmaceuticals and special nutrients. Now, the TFRD reports another tool to help rare disease patients: the Hsin Love World radio programme, airing every Saturday afternoon. The 60-minute programme invites rare disease patients and their families to come and discuss an array of topics concerning their condition with specially invited celebrities, including film directors, actors, and popular authors.

    In other news from Taiwan, the China Post newspaper reports that the Department of Health in Taipei is calling a meeting of experts to evaluate the efficacy of expensive treatment Zavesca (miglustat) for the indication of Niemann-Pick disease. The product has been administered under an experimental reimbursement scheme (50% government subsidised) for the last year. Zavesca received a negative opinion by the EMEA for extending its indication to Niemann-Pick disease last month. It is currently approved for type 1 Gaucher disease. Taiwan has less than ten known Niemann-Pick patients. The medicine costs roughly the equivalence of 6800 euros per patient per month for Niemann-Pick treatment in Taiwan.

    Genetic medicine handbook created for Australian physicians
    Australian general practitioners have a new tool at their fingertips: Genetics in Family Medicine: the Australian Handbook for General Practitioners is a web-based resource full of information for an array of genetic conditions, including some rare ones. Indeed, sections of the electronic handbook that can easily be downloaded and printed, include Chromosomal conditions, Clotting and bleeding conditions, Fragile X syndrome and other causes of developmental delay, Neurofibromatosis, and Neurological conditions. Other chapters of the handbook provide information on testing and pregnancy, newborn screening, and emerging genetic technologies.

    EU Project Follow-up
    Introducing DYSCERNE: A European Network of Centres of Expertise for Dysmorphology
    The Dyscerne Network was created to improve the diagnosis, management and information dissemination for rare dysmorphic syndromes. The main aims of the Dyscerne project include identifying centres of expertise for dysmorphology and creating a formal network of these centres. In addition, the group intends to develop a web-based electronic dysmorphology diagnostic system (DDS) enabling clinicians throughout Europe to submit difficult cases to an expert diagnostic panel. Finally, the project will develop diagnostic and clinical management guidelines for selected dysmorphic syndromes.

    The three-year project is funded by DG Sanco and is a partnership between six existing centres of expertise in dysmorphology from Belgium, France, Italy, the Netherlands, Poland and the UK. The University of Manchester is the coordinating partner for the project. The UK team is lead by Professor Jill Clayton-Smith from the Manchester Regional Genetic Service, and the project support team is based at the North West Genetics Knowledge Park (Nowgen). The Network had its formal launch in Manchester on 5 October 2007.

    A working prototype of the on-line diagnostic system will be piloted next Spring and is expected to be fully operational before the end of next year. Management guidelines for Noonan syndrome, Williams syndrome, 22q11 deletion syndrome and Angelman syndrome are scheduled to be completed by February 2010.

    For further information please visit the Dyscerne website or contact Project Manager Pam Griffiths by email or phone at +44 161 276 3209.


    Orphanet News
    New Texts
    New Orphanet Journal of Rare Diseases publications
    Oculocutaneous albinism
    Myasthenia gravis
    Arrhythmogenic right ventricular cardiomyopathy/dysplasia

    New Research Projects open for Recruitment
    Liver progenitor cell therapy for treatment of Crigler Najjar and Urea cycle defects (Belgium)
    Effect of Intranasal Administration of Orexine A on IL-6-System, Sleep-Wake-Regulation and Neurocognition (Germany)
    NOPHO-AML 2004 Study for Children With Acute Myeloid Leukemia (Denmark)


    New Genes
    Permanent neonatal diabetes has insulin gene mutation as cause
    Permanent neonatal diabetes is a very rare metabolic disorder that can be due to mutations in genes KCNJ11 and ABCC8. These genes encode two subunits of the ATP sensitive potassium channel expressed in the pancreas beta cells. In one family affected by an autosomal dominant form of the disease, the authors identified a mutation in the gene encoding insulin INS. They then observed mutations in this gene in two other families and in 13 patients presenting sporadic forms of the disease. The authors suggest that these mutations may prevent normal folding of proinsulin. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, potentially leading to severe endoplasmic reticulum stress and beta cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of beta cell function and mass. One of the human mutations reported here is identical to that in the Akita mouse.
    Read the PubMed abstract

    PNAS ; 15040-15044 ; September 2007
    Two children with herpes simplex encephalitis have mutations in a Toll family receptor
    Researchers identified a dominant negative mutation in gene TLR-3 in two children with a herpetic encephalitis infection caused by the herpes simplex virus-1 (HSV-1). This gene encodes the Toll-like 3 receptor implicated in natural immunity. Expressed in the central nervous system, TLR-3 may control the propagation of the HSV-1 virus, which could spread from the epithelium to the central nervous system via cranial nerves.
    Read the PubMed abstract

    Science ; 1522-1527 ; September 2007
    Schnyder crystalline corneal dystrophy may be due to mutations in UBIAD1 gene
    Schnyder crystalline corneal dystrophy (SCCD, MIM 121800) is a rare autosomal dominant disease characterised by progressive opacification of the cornea resulting from the local accumulation of lipids, and associated in some cases with systemic dyslipidemia. The authors found within a large multigenerational family in Nova Scotia affected with SCCD linkage to the area of chromosome 1 where UBIAD1 gene is located. Potential mutations in this gene have been identified in this family as well as four other small families of various geographic origins. UBIAD1 encodes a potential prenyltransferase and may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage.
    Read the PubMed abstract

    PLoS ONE ; e685 ; August 2007

    Research in Action
    Clinical Research
    Amyotrophic lateral sclerosis: a new susceptibility gene found
    Amyotrophic lateral sclerosis (ALS) is a devastating disease characterised by progressive degeneration of motor neurons in the brain and spinal cord. ALS is thought to be multifactorial, with both environmental and genetic causes. Some 90% of observed cases are sporadic. Two successive studies involving patients and controls demonstrated an association between a variant in the gene ITPR2, encoding inositol 1,4,5-triphosphate receptor 2 and sporadic forms of the disease. Moreover, ITPR2 expression was greater in the peripheral blood of 126 ALS patients than in that of 126 healthy controls. ITPR2 is a strong candidate susceptibility gene for ALS because it is involved in glutamate-mediated neurotransmission, is one of the main regulators of intracellular calcium concentrations, and has an important role in apoptosis.
    Read the PubMed abstract

    Lancet Neurol ; 869-877 ; October 2007
    Antiphospholipid antibodies (aPLA): P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis
    Antiphospholipid antibodies (aPLA) is characterised by arterial and/or veinous thrombosis, due, amongst other causes, to an increased expression of the adhesive molecules on the endothelial cells. The authors observed that the risk of thrombosis in patients presenting antiphospholipid antibodies is linked to a genotype of PSGL-1 This gene encodes a P-selectin ligand expressed in the leucocytes and acting in the adhesion to endothelial cells.
    Read the PubMed abstract

    Ann Rheum Dis ; 1378-1380 ; October 2007
    Asthma and hereditary allergies are frequent in classic and hypermobile forms of Elhers-Danlos syndrome
    Classic and hypermobile Ehlers-Danlos syndromes are diseases of the conjunctive tissues characterised by joint hypermobility, cutaneous hyperelasticity and tissue fragility. In contrast to the hypermobile form, patients with the classic form do not have atrophic cutaneous scarring. The authors have demonstrated a strong prevalence of asthma and allergies in a study of 288 patients and 221 controls. This elevated prevalence may be due to a linkage disequilibrium between the genes causing these conditions or to a putative immunologic effect of the connective tissue defect itself.
    Read the PubMed abstract

    Ann Rheum Dis ; 1369-1373 ; October 2007
    Testing for autoantibody presence can predict cancer risk in patients with myositis
    Although there is a known association between myositis and cancer, with a greater risk in dermatomyositis (DM) than polymyositis (PM), reliable methods to predict cancer risk in specific patients are not presently available. This study sought to determine whether risk of developing cancer in myositis can be predicted by antibody profiling. By analysing the presence of auto-antibodies linked to these diseases in 282 patients, they established a combination of tests for predicting cancer risk with 94% sensitivity and, specifically for dermatomyositis patients, 100% sensitivity. These results may help clinicians predict which patients with myositis are at greater risk of developing cancer, thus identifying those requiring aggressive diagnostic evaluation and intensive cancer surveillance at myositis onset and follow-up.
    Read the PubMed abstract

    Ann Rheum Dis ; 1345-1349 ; October 2007
    Gene Therapy
    Batten disease mouse models have improved motor functioning and survival outcomes via pre-symptomatic gene therapy
    Classical late infantile neuronal ceroid lipofuscinosis, or Batten disease, is a monogenic disorder caused by the loss of tripeptidyl peptidase 1 (TPP1) activity as a result of mutations in CLN2. Absence of TPP1 results in lysosomal storage with an accompanying axonal degeneration throughout the central nervous system, which leads to progressive neurodegeneration and early death. The authors injected an adeno-associated virus containing the CLN2 gene into the brain of mouse models. They demonstrated that gene therapy improved biochemical and functional disorders only if it is administered before the appearance of symptoms.
    Read the PubMed abstract

    Mol Ther ; 1782-1788 ; October 2007
    Gene therapy in limb girdle muscular dystrophy type 2D mouse models yields long-term skeletal muscle protection
    Limb girdle muscular dystrophy (LGMD) is a group of inherited diseases resulting from mutations in genes encoding proteins involved in maintaining skeletal muscle membrane stability. LGMD type-2D is caused by mutations in alpha-sarcoglycan (sgca). Administering human gene SGCA specifically in the muscle of adult mouse models of the disease via an adeno-associated virus, they observed long-term reduction in muscle fibre damage.
    Read the PubMed abstract

    Mol Ther ; 1775-1781 ; October 2007
    Therapeutic Approaches
    Fragile X symptoms reduced in mice by inhibiting p21-activated kinase
    Fragile X syndrome is the most commonly inherited form of mental retardation and autism. Different studies suggest a defect in dendrite structure. The authors analysed the inhibition of PAK, a kinase active in dendrite morphology, in Fragile X mice models. The expression of a negative dominant form of PAK in the proencephalon improves, at least partially, the synaptic morphology as well as the behaviour in the mice models. PAK thus represents a potential new therapeutic target.
    Read the PubMed abstract

    PNAS ; 11489-11494 ; July 2007

    Patient Management and Therapy
    Current spinal muscular atrophy research and practices delineated
    Spinal muscular atrophy is an autosomal recessive neurodegenerative disorder that affects the motor neurons responsible for movement of the proximal muscles of the trunk and body. In October, a group of experts gathered together to discuss current knowledge of the disorder. The result can be found in an article published in the Journal of Child Neurology, which covers diagnostic strategies, pathogenesis, therapeutic approaches, current clinical trials and future directions for research.
    Read the PubMed abstract

    J Child Neurol ; 926-945 ; August 2007
    Neurofibromatosis type 1: genetic counselling practice recommendations
    The Journal of Genetic Counseling has published an article proposing recommendations from the National Society of Genetic Counselors in the US for patients and families undergoing evaluation for neurofibromatosis type 1 (NF1) or who have received a diagnosis of NF1. The recommendations are based on the clinical experience of genetic counsellors as well as a review of the literature.
    Read the PubMed abstract

    J Genet Couns ; 387-407 ; August 2007
    Friedreich's ataxia: increasing idebenone dosage improves neurological functioning
    Friedreich's ataxia (FA) is a progressive, multisystem, degenerative disorder characterised by movement coordination trouble linked to cardiomyopathy, and caused by a reduction in frataxin. Loss of frataxin results in mitochondrial dysfunction and oxidative damage in patients and model systems. Previous studies have demonstrated that daily administration of the antioxidant idebenone reduces cardiac hypertrophy. In a 6-month, randomised, double-blind, placebo-controlled study, the authors showed that augmenting idebenone dosage was well tolerated by patients and improved neurological functioning. The degree of improvement correlated with the dose of idebenone, suggesting that higher doses may be necessary to have a beneficial effect on neurological function.
    Read the PubMed abstract

    Lancet Neurol ; 878-886 ; October 2007
    For sickle cell anaemia, hematopoietic stem cell transplantation improves survival
    Hematopoietic stem cell transplantation is presently the only curative treatment available for sickle cell anaemia. However, an associated high mortality level limits its use. In a retrospective study involving 87 patients, the authors observed that the principal indication for transplantation is the presence of a cerebral vasculopathy. With a median follow-up time of six years, the overall survival rate was 93.1%. The authors propose hematopoietic stem cell transplantation with an HLA-identical donor be integrated into the standard treatment management of patients presenting with an elevated risk for vascular accident.
    Read the PubMed abstract

    Blood ; 2749-2756 ; October 2007
    Gaucher disease type 1: miglustat maintains the condition of patients stabilised via enzyme therapy
    Gaucher disease type 1 was the first lysosomal disease to have an enzyme replacement therapy (ERT) available. ERT with imiglucerase administered intravenously reduces hepatosplenomegaly and improves hematologic parameters in Gaucher disease type 1 patients within 6-24 months. The authors evaluated the tolerance and efficacy of the oral administration of miglustat in 36 patients clinically stable after imiglucerase treatment. The patients remained stable and the miglustat was well tolerated. The authors suggest that miglustat could thus be an effective maintenance therapy in stabilized patients.
    Read the PubMed abstract

    Blood ; 2296-2301 ; October 2007
    Primary amyloidosis: High dose chemotherapy plus stem cell transplantation do not improve survival
    AL amyloidosis is characterised by the accumulation of amyloid fibres throughout the organism. Standard chemotherapy, based on the administration of melphalan, improves survival only for some months. The authors conducted a randomised trial with 55 AL amyloidosis patients comparing high-dose intravenous melphalan followed by autologous hematopoietic stem-cell transplantation with standard-dose melphalan plus high-dose dexamethasone. The results showed that the new treatment did not improve patient survival.
    Read the PubMed abstract

    NEJM ; 1083-1093 ; September 2007

    Orphan Drugs
    Seven EMEA orphan drug designations for November

    The COMP (Committee for Orphan Medicinal Products) adopted the following seven positive opinions on orphan medicinal product designation at its November meeting for the treatment of:

    - TERT positive nonsmall cell lung cancer in HLA-A2 positive patients
    - epithelial neoplasia of the vulva positive for human papilloma virus
    - prevention of cytomegalovirus (CMV) disease in patients with impaired cell medical immunity
    - pulmonary arterial hypertension including treatment of chronic thromboembolic pulmonary hypertension
    - hepatocellular carcinoma
    - acute myeloid leukaemia
    - gastric cancer

    Consult the European Registry for Orphan designations
    Consult the Orphanet list of orphan drugs authorised for marketing in Europe

    Genzyme receives Japanese marketing approval for Elaprase
    Genzyme Corp. has announced that it received marketing approval for Elaprase (idursulfase) in Japan for the treatment of Hunter syndrome (also known as mucopolysaccharidosis II). Elaprase is an enzyme replacement therapy developed by Shire Human Genetic Therapies Ltd. Genzyme is commercialising the product in Japan and other Asia Pacific countries. Elaprase is the fifth enzyme replacement therapy introduced in Japan by Genzyme.
    Change in Storage Conditions for Humate-P approved by FDA
    The U.S. Food and Drug Administration (FDA) has approved a change in the storage conditions for Humate-P, a treatment for bleeding in some patients with hemophilia A or von Willebrand Disease. The treatment is a protein that helps blood form the clots necessary to stop bleeding. It can now be safely stored for up to two years at 25 degrees Celsius (77 degrees Fahrenheit). Humate-P previously required colder, refrigerator-level temperatures for this storage length. Approval of this change was based on stability data that includes laboratory tests of product potency conducted under different temperatures submitted by the manufacturer, CSL Behring GmbH.

    News from the Patients' Associations
    News update: Marathoner goes all the way for ataxia telangiectasia
    You may remember that we reported on California athlete Tim Borland in the 25 September issue of OrphaNews Europe as he set out to run 63 marathons in 63 days across the United States, often pushing a child with ataxia telangiectasia (AT) in a stroller or wheelchair. Borland made running history as he finished up his run at the New York City Marathon on 4 November. Not only did his A-T CureTour raise funds for the incurable autosomal recessive disorder that combines severe humoral and cellular immune deficiencies and progressive cerebellous ataxia, maybe more importantly, it raised awareness for AT and other rare disorders all across America.

    Courses & Educational Initiatives
    Clinician scientist fellowship programme
    Molecular Medicine Ireland is a non-profit institution established by the National University of Ireland Galway, the Royal College of Surgeons in Ireland, Trinity College Dublin, University College Cork, and University College Dublin, building and expanding on the success of the Dublin Molecular Medicine Centre. Molecular Medicine Ireland now invites suitably qualified medical graduates to apply to their three-year Clinician-Scientist Fellowship Programme in translational medical research.
    For further information and application forms


    What's on Where?
    4th European Conference on Rare Diseases (ECRD 2007)
    Date: 27-28 November 2007
    Venue: Lisbon, Portugal

    This important rare disease conference will be held in English and simultaneously translated into French, German, Portuguese and Spanish. Several satellite meetings are being organised the day before the conference, including a Workshop on Rare Disease Help Lines.
    To register for the workshop.
    More details

    15th Annual Meeting International ALS/MND Associations Alliance
    18th ALS/MND International Symposium

    Date: 1-3 December 2007
    Venue: Toronto, Canada
    More details

    CDBI Seminar on Predictivity, Genetic Tests and Insurance
    Date: 3-4 December 2007
    Venue: Strasbourg, France

    The Steering Committee on Bioethics (CDBI) of the Council of Europe presents this seminar designed to provide a general overview of predictivity, genetic testing and insurance, and identify relevant issues to be addressed.
    For further details

    2nd Annual Rare Disease Leadership Summit
    Date: 5-6 December 2007
    Venue: Washington, DC US

    On the 25th anniversary of the US Orphan Drug Act, this conference, gathering together industry stakeholders and other rare disease/orphan drug experts, will provide case studies and panel discussions on financial, clinical, marketing and reimbursement considerations for successful orphan drug development.
    More details

    East Meets West in Rare Diseases
    Date: 6-7 December 2007
    Venue: Soesterberg, Netherlands

    This workshop, hosted by the Dutch Steering Committe on Orphan Drugs, facilitates an exchange of expertise on rare disease care, cure and research topics between Eastern and Western European stakeholders.
    For further information

    Lowe Syndrome Second International Symposium
    Date: 7 December 2007
    Venue: London, England

    Molecular and clinical advances in Lowe syndrome.
    More details

    EuroGentest Workshop: Towards Accreditation-Managing the Human Side of Change
    Date: 7-8 February 2008
    Venue: Nice, France

    Within the context of introducing quality management leading toward accreditation, this workshop addresses overall insights into the 'human, behavioural' side of change with techniques to manage this part of the change process, using case studies and role play to help apply these insights and techniques to real life situations.
    More details

    Rare Diseases: Channels and Transporters
    Date: 8-12 March 2008
    Venue: Sant Feliu de Guixols, Spain

    The conference is devoted to channels and transporters involved in rare inherited diseases. Specifically TRP and CLC channels, connexins, mitochondrial transporters, heteromeric amino acid transporters, neurotransmitter transporters, ABC transporters and related diseases will be covered.
    For further details

    ICORD 4th International Conference on Rare Diseases and Orphan Drugs
    Date: 20-22 May 2008
    Venue: Washington, DC US
    For further details

    14th International Conference on Prenatal Diagnosis and Therapy
    Date: 1-4 June 2008
    Venue: Vancouver, Canada

    Conference sessions will include foetal imaging, cytogenetics, foetal DNA/RNA, PGD, screening, teratology, and legal aspects of prenatal diagnostics and therapy. The deadline to submit an abstract for this conference is 4 February 2008.
    For further details

    Fourth International Neuroacanthocytosis Symposium: Bridging Clinical and Basic Aspects
    Date: 1-2 July 2008
    Venue: Oxford and London, England

    Including clinical aspects of chorea acanthocytosis and McLeod syndrome, muscle and nerve neuropathology and syndromes related to NA.
    For further details

    Genetic Alliance Annual Conference 2008
    Date: 11-13 July 2008
    Venue: Bethesda, MD, US

    Brings advocates, health professionals, policy makers, industry representatives, researchers, and community leaders together for workshops and discussions. The deadline for submitting abstracts for this conference is 30 November 2007.
    For further details

    6th World Rett Syndrome Congress
    Date: 10-13 October 2008
    Venue: Paris, France

    Various aspects of Rett syndrome and MECP2 functioning, including fundamental, clinical and management topics.
    For further details


    Press & Publications
    Interesting rare disease reading in the British Paediatric Surveillance Unit Annual Report
    The British Paediatric Surveillance Unit (BPSU) of the Royal College of Paediatics and Child Health has recently published its 21st Annual Report. This report highlights current paediatric rare disease surveys facilitated by the BPSU, including congenital rubella, MCADD, neonatal herpes, and sceloderma. The report also includes information on the 60 other rare paediatric conditions surveyed over the past 20 years. A copy of the report is available electronically on the BPSU website. Hard copies are also available by emailing the BPSU.

    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, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
    For more information on the Rare Diseases Task Force
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