Editorial
The EUCERD 2012 Report on the State of the Art of Rare Disease Activities in Europe offers comprehensive information on EU and Member State initiatives
The annual report on the State of the Art of Rare Disease Activities in Europe of the European Union Committee of Experts on Rare Diseases is now available online. This elaborate report, produced by the Scientific Secretariat of the European Union Committee of Experts on Rare Diseases (EUCERD) under the framework of the EJA (EUCERD Joint Action), provides a comprehensive overview of rare disease and orphan drug activities at both the European Union (EU) and Member State (MS) levels up through the end of 2011 - including the progress of EU Member States in meeting the Council Recommendation for developing a national strategy for rare diseases. Composed of five volumes, new and particularly noteworthy this year is Part II, Key developments in the field of rare diseases in Europe in 2011. For readers who have read previous years’ reports and are well versed in the activities in the field, this volume offers a synthesis of all the activities taking place in 2011. Amongst topics reported at both the MS and EU levels are the development of centres of expertise; registries; genetic testing resources and activities; patient organisation activities; information resources; guidelines and recommendations; educational initiatives; research and funding mechanisms and participation in EU-level projects; rare disease conferences and events; orphan medicinal product incentives, availability, reimbursement and pricing policies; and specialised social services. Each section of the report includes a bibliography of sources used, including a list of any European Commission documents referred to and a list of web addresses organised by country listing national sources of information on rare diseases and links to documents concerning national plans or strategies for rare diseases when appropriate. The report also furnishes the list of contributors, organised by country and with mention of the validating authority for each country. The report, useful to stakeholders from all rare disease and orphan drug areas, is freely accessible via the EUCERD website.
EUCERD Report: 2012 Report on the State of the Art of Rare Diseases Activities in Europe:
Part I: Overview of Rare Disease Activities in Europe - July 2012
Part II: Key developments in the field of rare diseases in Europe in 2011 - July 2012
Part III: European Commission activities in the field of rare diseases - July 2012
Part IV: European Medicines Agency activities and other European activities in the field of rare diseases - July 2012
Part V: Activities of European Member States and other European countries in the field of rare diseases - July 2012
Spotlight on...
Improving rare disease patient care and research in Germany: the Baden-Wurttemberg state-wide network of Rare Disease Centres
Rare disease experts from Germany describe for OrphaNews Europe how their country is implementing centres for rare diseases, building upon the existing infrastructure and framework of the German healthcare system:
Over the last years, Rare Disease Centres (RDCs) have been installed in several academic medical institutions in Germany. In the future, RDCs will include non-academic hospitals and members involved in patient care and advocacy groups as well. National and international experience has clearly demonstrated that RDCs have to rely on the existing institutions and have a coordinative function rather than setting up additional capabilities. Even in large RDCs, the expertise is different, according to the local emphasis in research and clinical care. It has become evident that national, regional or cross-border Reference Networks (RNs) are the best solution for organising rare disease resources, such as the European Reference Network (ERN) discussed at the Fifth meeting of European Union Committee of Experts on Rare Diseases in Luxembourg in June 2012.
In Germany, the coordination of clinical capacities is largely attributed to the regional states, rather than to the national bodies, based on the national constitution. When RDCs were established at the academic medical institutions in Freiburg, Heidelberg, Mannheim, Tuebingen, and Ulm, structure and interests were discussed at regular meetings. The group decided:
For more information contact Prof. Frank Lehmann-Horn
EU Policy News
The squeaky wheel really does get the grease!
After much campaigning, the EU Clinical Trials Directive to undergo revision
As has been reported extensively in this newsletter and elsewhere, the EU Clinical Trials Directive (2001/20/EC), which delineates the legal requirements for conducting clinical studies in the European Union, has been blamed for increasing the costs and time to launch trials due to burdensome and complex administrative procedures. Amidst fears that the Directive is driving medical research out of the European Union, various pleas and petitions from an array of stakeholders have called for urgent revision. In response, the European Commission has announced plans to replace the Directive via a new Regulation that would continue to ensure patient safety while simplifying related administrative tasks and promoting multinational studies. This announcement is considered good news for the rare disease research community as well as other healthcare stakeholders across the EU.
Learn more
DG SANCO
Five rare disease projects selected for funding under the 2012 work plan of the Second EU Health Programme
The European Commission has made the Award Decision concerning the projects, joint actions, conferences and operating grants to be co-funded following the Calls for Proposals under the 2012 work plan of the Second EU Health Programme (2008-2013). A call for proposals was published on 8 December 2011 with a view to selecting proposals eligible for European Union funding under the work plan for 2012. The deadline for submitting proposals under the call was 9 March 2012. In the area of rare diseases a total of five projects on information networks and registries have been selected:
In addition, two rare disease Operational Grants were selected for funding:
DG Research
European Commission issues FP7 call for proposals in the health field with one call specific to rare diseases
The Seventh Framework Programme (FP7) for Research and Technological Development is the EU's main instrument for funding research in Europe and runs from 2007 to 2013.The European Commission in July published calls for proposals in various thematic areas of the FP7, including the Cooperation Specific Programme, which includes the Health Theme. This year, only one specific rare disease topic is included: Development of imaging technologies for therapeutic interventions in rare diseases. A call for collaboration has been issued in this newsletter by stakeholders preparing an application in response to this call (learn more). The deadline for application for the FP7 call is 2 October 2012.
Learn more about the FP7 call
DG Research consultation seeks views on public-private partnership initiatives in health research
Public-private collaboration is considered crucial in the field of rare disease and orphan drug research, an area that suffers from a lack of resources and funding. Under the 7th Framework programme for research, technological development and demonstration activities (2007-2013) (FP7) the European Union (EU) entered into a Public Private Partnership (PPP) with the pharmaceutical industry, represented by its umbrella organisation European Federation of Pharmaceutical Industries and Associations (EFPIA). The Innovative Medicines Initiative (IMI) was established by Council regulation 73/2008 of 20.12.2007. Both partners contribute € 1 billion each to implement IMI. With this funding IMI is Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients – including rare disease medicinal products. Based on the success of IMI the European Commission is now exploring whether under Horizon 2020 a renewed PPP should be launched. The Commission proposal for Horizon 2020 foresees that the priority "societal challenges" is also implemented through PPPs. Selection of PPPs will be based on a set of clearly defined criteria, including the added value of action at the EU level, the scale of impact on industrial competitiveness, sustainable growth and socio-economic issues, and the long-term commitment from all partners based on a shared vision and clearly defined objectives. As part of this process a public consultation is being conducted. The consultation seeks key views relating to the launch of a PPP in the life sciences research area under Horizon 2020 and what areas should be addressed. The deadline for responding to the consultation is 4 October 2012.
Learn more
EMA
European Medicines Agency makes available prevalence data sources for orphan-designated conditions
As part of a general growing trend toward sharing data and resources in the interest of facilitating rare disease and orphan drug information and research, the European Medicines Agency (EMA) has created a table of relevant sources for prevalence data for orphan conditions. The sources included in the document were validated by the Committee for Orphan Medicinal Products (COMP) during the evaluation of orphan designation applications. The table, publicly available, will be updated on a regular basis. While sponsors are still required to submit original, verifiable, current prevalence data with their application for an orphan designation, the table is considered a useful resource for facilitating access to such data. Orphan designated medicinal products are indicated for conditions that affect 5 persons or less per 10,000 of the population in the EU. Determining prevalence can be challenging for stakeholders. The new table lists the sources, such as relevant scientific literature, registries and databases, used to determine prevalence for a condition at the time an orphan designation was sought.
Learn more
Increasingly transparent: EMA prepares to make clinical trial data available
The European Medicines Agency (EMA) recently announced that it will proactively publish clinical trial data and enable access to full data sets by interested parties. As there are a number of practical and policy issues that need addressing before complex data sets can be made available, a workshop will be held on 22 November 2012 to discuss topics relating to this evolution. The workshop seeks to elicit the views and concerns from a broad range of institutions, groups and individuals in order to help the Agency define the modalities of proactive access to clinical trial data. Registration for the workshop is open until 31 October 2012.
Learn more
EMA re-launches call for patient and healthcare-professional committee representatives
The European Commission has re-launched a call for expressions of interest from representatives of patient and healthcare-professional organisations who wish to sit on the Committee for Advanced Therapies or the Pharmacovigilance Risk Assessment Committee. The deadline for submitting an expression of interest is 1 October 2012.
Learn more
National & International Policy Developments
Patient-Centered Outcomes Research Institute seeks comments on new methodology report
The independent, non-profit Patient-Centered Outcomes Research Institute (PCORI) conducts research in order to provide information about the best available evidence to help patients and their health care providers make more informed decisions. PCORI’s research is intended to give patients a better understanding of the prevention, treatment and care options available, and the science that supports those options. PCORI is seeking input on their Draft Methodology Report, which proposes standards for the conduct of patient-centered outcomes. This first draft report focuses on the patient’s perspective, while future reports will address the perspectives of clinicians, healthcare purchasers and policy-makers in more detail. The deadline for submitting comments is 14 September 2012.
Learn more
New bill in USA hailed by rare disease stakeholders as momentous step forward for patients seeking treatments
In July, President Barack Obama signed into law the U.S. Food and Drug Administration (FDA) Safety and Innovation Act, qualified by the USA’s National Organization for Rare Disorders stakeholders as “the most groundbreaking measures for rare disease patients and their families since the Orphan Drug Act of 1983”. The Act ushers in several significant changes including “accelerated patient access to new medical treatments; the development of Humanitarian Use Devices, or medical devices for small patient populations; accelerated development of "breakthrough therapies"—those that show early promise; enhanced consultation with rare disease medical experts; a rare pediatric disease priority review voucher incentive program; and resolution of conflict-of-interest issues related to FDA advisory committee participation”.
Learn more
Other European news
Rare disease initiatives underway in Bulgaria for rare disease diagnostics, expert centres
According to a recent news report, plans are underway in Bulgaria, initiated by stakeholders at St Marina University Hospital in Varna, to create the country’s first centre for rare disease diagnostics. Initially, the centre would focus on haemophilia and thalassaemia. Bulgarian Minister of Health Desislava Atanasova is reported as announcing that the centre would be part of a larger European network and would start operating in March 2013. At the upcoming Bulgarian 3rd National Conference for Rare Diseases and Orphan Drugs (taking place from 14-15 September 2012) rare disease centres of expertise (CoE) will be a principal topic for discussion. A panel of experts will focus on the EUCERD proposed criteria for CoE designation with the eventual goal of adopting a set of designation criteria that could be proposed to the Ministry of Health. In other news, the Bulgarian Information Centre for Rare Diseases and Orphan Drugs has released a new report listing the epidemiological registries for rare diseases in Bulgaria Learn more.
Developing genetic services within mainstream clinical services
In the United Kingdom, a report of the Joint Committee on Medical Genetics identifies the challenges inherent in integrating genomic medicine into the wide range of existing clinical areas. Evolving genetic technologies are creating an important impact in the field of healthcare and patient outcomes, through their capacity to predict, diagnose and treat both rare and common disorders. Genetics is proving particularly useful to help stratify population cohorts and provide more personalised medicine. Amongst the points raised in the report, is the need for genetics sub-specialist training in existing clinical areas such as paediatrics and antenatal care. The report encourages the development of such training to complement and collaborate with existing genetics infrastructures. To combat inequity in the availability of access to specialist centres for heritable disorders, the authors recommend “the formal inclusion in the new commissioning structures of resourced, multidisciplinary expert groups, which may be specialty or disease specific depending on the context, able to give advice (via Public Health England or otherwise) on specifications for quality assured pathways to assist commissioners”. The report is available via the website of the Foundation for Genomics and Population Health.
Consult the report
Bioinformatics, Registries and Data Management
An example of a successful interoperable Internet-based rare disease registry for multiple stakeholder use in dispersed geographic regions
An article appearing in Human Mutation describes the successful design and implementation of an Internet-based rare disease registry, delineating how the open source system, interoperable with other networks and systems, has successfully been adopted for specific rare diseases in Australia, enabling clinicians and trial sponsors to efficiently identify patients for specific studies in a secure, privacy protected environment.
Consult the PubMed abstract
Ethical, Legal & Social Issues
Learning from ethical disagreement around high risk paediatric research involving novel therapies
An intriguing article published in Molecular Therapy explores the ongoing debate around high risk research in paediatric patient populations, asserting that analysing areas of disagreement in the field can reveal current practices and areas in need of further exploration and development. Using paediatric trials involving gene transfer technologies for the rare disease late infantile neuronal ceroid lipofuscinosis as an example, the authors assert that the ethical implications raised are applicable to other high-risk paediatric research. Focusing particularly on what constitutes a “prospect of direct benefit” in phase I trials and when risk is justified by the anticipated benefit in gene therapy studies, the authors conclude that considerations of risk and benefit involve value judgements, which must be rendered transparent in order to be critically evaluated. Current disagreements reveal a lack of adequate regulation in the field, which the authors assert must be revised in order to distinguish between trials involving different degrees of evidential support in the areas of benefit/risk. As a vast majority of paediatric prescriptions still involve unlicensed or off-label practice, further enquiry in this area is needed, particularly for chronic, life-threatening conditions in paediatric patients.
Consult the PubMed abstract
EU Project Follow-up
EuroWilson: a European Network improving the management of Wilson disease
Wilson disease is an autosomal recessive disorder characterised by the toxic accumulation of copper, mainly in the liver and central nervous system. The disease results from mutations in the ATP7B gene on chromosome 13. The discovery of the gene has led to a better understanding of cytosolic copper trafficking and its relationship with ceruloplasmin synthesis. This disease can be efficiently treated by chelation and zinc therapy. Liver transplantation is the recommended therapy for patients with fulminant hepatitis, or in those with relentless progression of hepatic dysfunction despite drug therapy. EuroWilson is a multi-stakeholder network with 67 scientific country coordinators from 19 countries. Originally funded (from 2004-2008) through the European Commission Sixth Framework Programme (LSHM-CT2004 503430), in 2011, EuroWilson received funding from the European Commission Directorate General for Health and Consumers Operating Grant. It is currently hosted by the Assistance Publique Hopitaux de Paris. Its mission is to improve the quality of care and access to multidisciplinary expertise for European patients with Wilson disease. The main objectives are to shorten the delay to diagnosis and to decrease the inequalities between each European country. EuroWilson has initiated several activities to reach these goals. In order to facilitate physician access to more detailed information about Wilson disease, the EuroWilson website has been developed to provide information about the disease and relevant resources. The network shares knowledge gained during meeting and phone conferences between health professionals and publishes an online quarterly journal called Wilson Disease Watch which includes an overview of the latest medical and scientific publications. The EuroWilson Network also participated in creating the European guidelines on Wilson disease. The network has operated a registry for newly diagnosed patients since 2005 in order to increase understanding of the disease and to evaluate the feasibility of therapeutic trials for Wilson disease. Patient empowerment is also very important within this European network. With the collaboration of the patient representatives, the network set up a survey to better define patients’ priorities and expectations from a European network. The results of this survey underline a real inequality in the management of this disease and the necessity to improve the collaboration between local and national organisations. With the input from patients, the network will continue to evaluate inequalities in Europe, especially in the area of access to treatment. This European network needs sustainability in order to continue fulfilling its objectives for Wilson disease – a treatable condition, when diagnosed early.
Learn more about EuroWilson
Orphanet News
Orphanet gets a new look – improving accessibility to its rich trove of informational resources for rare diseases and orphan medicinal products
The Orphanet homepage got a makeover this summer. Intended to meet the needs of site users who asked for a less cluttered, more user-friendly homepage, the streamlining provides easier access to the numerous services offered by Orphanet, the pan-European informational database for rare diseases and orphan drugs. Consequently, some of Orphanet’s lesser known information resources are enjoying better visibility and will hopefully benefit a wider audience. The ergonomics of the new Orphanet homepage have been designed to enhance usability, with specific emphasis on improving accessibility for visually impaired users. The typeface has been magnified and information organised in easy-to-spot blocks that permit users to more readily navigate the site. The disease search function remains in the center of the homepage, while the old system of tabs for Orphanet’s other principal resources has been re-organised into a table of contents. The popular Orphanet Report Series, which address relevant rare disease and orphan drug topics, are now highlighted in a specific framework. Finally, OrphaNews is easily identified in the top right. The Orphanet team hopes that this new design will arouse curiosity and encourage site users to discover - or rediscover - the large array of freely accessible high quality rare disease resources and services available via Orphanet.
View the new Orphanet homepage
New Texts
New rare disease emergency guidelines available in Italian, Portuguese and Spanish
Orphanet provides rare disease emergency care guidelines to be distributed to emergency and intensive care hospital units and also made available on the Orphanet website. New guidelines are now available in Portuguese for:
diabetes insipida central
cystic fibrosis
antiphospholipid syndrome
nephrogenic diabetes
Emergency guidelines are available in Italian for:
Steinert myotonic dystrophy
vascular Ehlers-Danlos syndrome
Emergency guidelines are available in Spanish for:
Duchenne muscular dystrophy
Autoimmune myasthenia
New Syndromes
A newborn with features mimicking a short rib syndrome but suggesting a ciliopathy
The authors report on a male infant born to consanguineous parents, died 6 hours after birth, and presenting with a syndrome resembling that described by Cideciyan et al. in 1993. Clinical examination detected hydrocephalus, right anophthalmia, left microphthalmia, cleft palate, midline cleft of lip, microphallus, empty scrotum and marked lymphedema with constriction rings at elbows and wrists. Autopsy revealed pulmonary bronchial lymphangiectasia, hepatic periportal fibrosis, adrenal agenesis, ventricular septal defect, aortic stenosis, and undescended testes. Radiographs exhibited short limbs and mild shortness of ribs. According to the authors these features are different from any known short rib syndrome and suggest a new ciliopathy. Though this condition shares similarities with Meckel syndrome, the authors suggest it is a distinct entity.
Consult the PubMed abstracts
Am J Med Genet ; 255-9 ; 15 May 1993
A leucoencephalopathy with ischemic stroke, retinitis pigmentosa and dysmorphic syndrome linked to chromosome 17q24.2-25.3
The authors studied a consanguineous family with three members suffering from hereditary leucoencephalopathy with ischemic stroke, retinitis pigmentosa and dysmorphic syndrome combining, depending on the cases, some of the following features: oblong face, hypertelorism, arched palate, pes cavus, and equinovarus, dorsal scoliosis, and macroglossia. Molecular studies allowed to map this new clinical entity to a locus on chromosome 17q24.2-25.3 in a chromosomal segment of 11 Mb.
Consult the PubMed abstract
Multiple congenital anomalies associated with developmental and mental delay in two brothers
Multiple congenital anomalies and mental delay have been observed by the authors in two brothers born to a couple of second cousins. The similar findings between the two children are developmental and mental delay, hypotonia, brachycephaly with craniosynostosis, pyloric stenosis, bilateral cryptorchidism, low-set and large ears, high-arched wide palate, pectus excavatum, thalassemia intermedia, inability to hold the head straight and to sit. Clinically, neurologically and from a molecular point of view, these anomalies don’t match exactly any known syndromes manifesting with some of these manifestations, such as Apert, FG, Floating-Harbor, Shprintzen-Goldberg and Rett syndromes. Therefore the authors think that it is a new syndrome apparently transmitted in an autosomal recessive manner.
Consult the PubMed abstract
Tetrasomy 15q26 is a distinct syndrome
The authors studied four patients carrying tetrasomy for regions distal to 15q25, i.e. regions ranging from 15q26 to 15qter, in the form of a neocentric chromosome. They observed that these patients share a flagrantly more consistent phenotype than do the cases suffering from Shprintzen-Goldberg syndrome, a disease resembling clinically tetrasomy distal 15q but characterized by more variegated manifestations and genetically heterogenous. Thus the authors conclude that tetrasomy 15q26 is a distinct syndrome.
Consult the PubMed abstract
New Genes
GPSM2 mutations induce hearing loss and brain malformations characteristic of Chudley-McCullough syndrome
Mutations in the mitochondrial methionyl-tRNA synthetase cause autosomal recessive spastic ataxia with leukoencephalopathy
Childhood-onset proximal spinal muscular atrophy, autosomal dominant: mutations in the tail domain of DYNC1H1 disrupt dynein complex assembly and function
Familial atrial fibrillation: predisposition with GATA5 mutations and early-onset form with KCNE1 mutations leading to gain-of-function of Iks current
BMC Med Genet. ; 24 ; 3 April 2012
Idiopathic and/or familial pulmonary arterial hypertension: mutations in CAV1 highlight the role of caveolae in the homeostasis of the pulmonary vasculature
Hirschsprung disease is associated with NRG3 copy number variations
Mitochondrial disease with hypertrophic cardiomyopathy: the heart impaired by mutations of MTO1 involved in mitochondrial tRNAs modification
GRN mutations associated with adult neuronal ceroid lipofuscinosis when homozygous and with a frontotemporal lobar degeneration when heterozygous
RAD21 mutations induce a phenotype consistent with a cohesinopathy and that overlaps with Cornelia de Lange syndrome but with milder symptoms
Juvenile neuronal ceroid lipofuscinosis is caused by anomalies of ATP13A2 also mutated in Kufor-Rakeb syndrome, a rare Parkinsonian phenotype
TRDN mutations leading to absence of triadin cause autosomal recessive catecholaminergic polymorphic ventricular tachycardia
Loss-of-function of CAMTA1, a brain-specific calcium responsive transcription factor, is responsible for spinocerebellar ataxia type 29
Situs ambiguous and situs inversus totalis: CCDC11 mutation results in an abnormally smaller protein associated with impaired L-R asymmetry
Agnathia-holoprosencephaly-situs inversus: an involvement of OTX2 apparently not sufficient and suggesting a second genetic hit
Research in Action
Fundamental Research
Smith-Magenis syndrome: RAI1 mutations disrupt circadian rhythm through dysregulation of CLOCK transcription and maybe other channels
Altered Ca2+ signaling could be a central mechanism in the development of infantile neuroaxonal dystrophy
Friedreich ataxia: a negative feedback mechanism involving oxidative metabolism and cardiac mitochondrial protein acetylation
Leber congenital amaurosis: Pals1 conditional knock-out mice exhibit the characteristics of human patients
A negative correlation between ZPR1 levels and the severity of proximal spinal muscular atrophy in mice suggests a role of protective modifier for this protein
Lipid-based nanoparticle delivery of Pre-miR-107 inhibits the tumorigenicity of squamous cell carcinoma of head and neck in vitro and in mice
The ephrin receptor tyrosine kinase A2 is an entry receptor for Kaposi’s sarcoma–associated herpes virus
Fragile X-associated tremor/ataxia syndrome: a role for miRNA and its selective mRNA targets in rCGG-mediated neurodegeneration
Young adult-onset of Parkinsonism: ATP13A2 deficiency induces lysosomal alterations and death of ATP13A2 knockdown dopaminergic cells
Clinical Research
GTP cyclohydrolase I deficiency: prenatal dopaminergic replacement therapy prevents impairment of mental abilities
Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal subsequent malignant neoplasms
Juvenile idiopathic arthritis: aggressive early treatment results in clinical inactive disease at 6 months and clinical remission on medication at 12 months
Women with systemic sclerosis have a higher-than-normal risk of preterm delivery, intrauterine growth restriction, and babies with very-low birth weight
Congenital factor XIII deficiency: recombinant factor XIII is safe and effective in preventing bleeding episodes
Chronic B-cell lymphocytic leukemia: fludarabine and cyclophosphamide can kill previously untreated patients when in combination with alemtuzumab
Somatic mosaicism of NEMO is frequent in T cells of patients with hypohidrotic ectodermal dysplasia with immunodeficiency
B-cell non-Hodgkin lymphoma: anti-CD 20 obinutuzumab induction and maintenance therapy is well tolerated with promising efficacy
Cystic fibrosis: inhaled hypertonic saline offers no advantage over isotonic saline in decreasing pulmonary exacerbations in infants and young children
Cushing syndrome: six months of mifepristone, a glucocorticoid receptor antagonist, produce clinical and metabolic improvement
Decreased incidence of cancer in patients with polyglutamine diseases: does polyQ-tract expansion have protective role?
Adrenocortical carcinoma: higher antitumor efficacy but same overall survival with mitotane when associated with EDP than when combined with streptozocin
Inhibiting the hedgehog pathway is efficacious in preventing and treating Gorlin syndrome
Gene Therapy
Wiskott-Aldrich syndrome: effective WAS gene transfer and restoration of expression and function of WASp in lymphoid and myeloid lineages of mice
Idiopathic pulmonary fibrosis: SB-mediated miR-29 gene therapy inhibits bleomycin-induced pulmonary fibrosis in mice
Duchenne muscular dystrophy: antisens sequences in U7 small nuclear RNA induce efficient exon skipping in patients’ myoblasts and in vivo in mice
Severe combined immunodeficiency due to adenosine deaminase deficiency: retroviral gene correction restores central and peripheral B cell tolerance in patients
Very long chain acyl-CoA dehydrogenase deficiency: long term correction of several symptoms with VLCAD transfer in mice
Therapeutic Approaches
A human neuronal model of Niemann-Pick disease type C shows that neuronal injury is linked with autophagy failure
Cutis gyrata-acanthosis nigricans-craniosynostosis: p38 kinase inhibition ameliorates skin and skull abnormalities in a mouse model
A peptide derived from endostatin prevents and reverses dermal and pulmonary fibrosis in vivo in mouse, in vitro and ex vivo in human
Diagnostic Approaches
Leber congenital amaurosis: massively parallel sequencing allows accurate, fast, and cost-effective early molecular testing
Patient Management and Therapy
Seizures and epilepsy within the context of encephalopathies and X-linked intellectual disability
Incontinentia pigmenti: a review of neurological findings
Orphan Drugs
Regulatory News
Two new orphan drugs approvals under the FDA's accelerated programme
In the USA, the Food and Drug Administration has approved Marqibo (vincristine sulfate liposome injection) to treat adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukaemia (ALL), a rapidly progressing blood and bone marrow cancer that is more commonly diagnosed in children than adults. Marqibo, approved under the FDA’s accelerated approval programme for patients whose leukaemia has relapsed two or more times, or whose leukaemia has progressed following two or more regimens of anti-leukaemia therapy, is marketed by Talon Therapeutics. An orphan designation was granted for vincristine sulphate liposomes in July 2008 by the European Commission, for the treatment of acute lymphoblastic leukaemia.
The FDA also granted accelerated approval to carfilzomib injection (Kyprolis, Onyx Pharmaceuticals) for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of the last therapy.
CHMP adopts positive opinion recommending a new contraindication for Volibris
On 21 June 2012, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a variation to the terms of the marketing authorisation for the medicinal product Volibris (ambrisentan) (Glaxo Group Ltd). The CHMP adopted a new contraindication for idiopathic pulmonary fibrosis with or without secondary pulmonary hypertension.
Learn more
Grants
Swiss Sanfilippo Foundation issues call for proposals
The Swiss Sanfilippo Foundation is a non-for-profit organisation whose main mission is the development of a treatment for patients afflicted by Sanfilippo disease (mucopolysaccharidosis type III). In addition to the currently funded programmes, the Foundation intends to support new development projects in the fields of, but not limited to, stem cells, genetic engineering, delivery of medications through the blood brain barrier, enzyme replacement therapy, chaperone and substrate reduction therapies and repurposing of existing drugs. Funding grants (between 20 000 - 100 000 Swiss Francs) (€16 654 - €83 000) are available immediately. Inquiries or development proposals (in the form of a 2-4 page document) can be sent by email to info@fondation-sanfilippo.ch.
Learn more
Partnersearch, Job Opportunities
Call for collaboration issued in response to FP7 call for proposals in the area of rare disease imaging technologies for therapeutic interventions
Thales Electron Devices, located near Grenoble, is the world’s largest production centre dedicated to X-ray medical radiology and the supplier of 90% of worldwide equipment manufacturers, accounting for nearly 50% of worldwide production of image intensifiers, and the world leader for digital flat-panel detectors. One out of two X-ray exams performed globally uses a Thales detector. Thales also develops imaging solutions covering the whole software chain, from detection to the complete clinical imaging function, while continuing to reduce the dose received by the patients and medical staff, in both the diagnostic and interventional domains. Now, Thales proposes to research advanced imaging for therapeutic interventions in rare diseases, by studying the interest of increased performance of X-ray imaging (2D and eventually 3D) when added to new imaging modalities such as molecular and multimodal. This approach is in line with the call for proposals in the 7th Framework Programme of the European Union related to Health, published on 10th July 2012 and entitled FP7-HEALTH-2013-INNOVATION-1 1.2-1: Development of imaging technologies for therapeutic interventions in rare diseases (see above). Thales would be interested in working with potential partners in the rare disease clinical expertise domain in order to identify pathologies that could be addressed and the possible consortia that could be eventually formed. For more information, contact Kim Pham at Thales Electron Devices (Telephone: +33-1-30-70-36-31)
Orphanet seeks an information scientist/data manager in the field of rare diseases and orphan drugs
Job description
Collect data on on-going research activities in the field of rare diseases and orphan drugs. Organise the data by type of research and stage of development. Publish the data in Orphanet (www.orpha.net). Analyze the data for reports.
Team activity
Position at an INSERM service with forty professionals fully dedicated to database management, data collection and data publication. The position is within a team of four people but requires interaction with other members of the service.
Qualification and experience
Background in biology or medicine or pharmacy with experience in research required. Good capacity to use information technologies. Training or experience in scientific documentation. Fluency in English is required.
Contract
One-year contract, renewable for six years.
Salary
Salary according to the scale of the public institutions in France, dependent on the diplomas and acquired experience in relevant position(s).
Working hours
38.30 per week and 47 days of vacation annually. Flexible hours.
Employing institution
INSERM
101, Rue de Tolbiac
75654 PARIS Cedex 13
Location of the job
INSERM US 14
Rare Disease Platform
96 Rue Didot
75014 PARIS
Contact:
Dr Ségolène Aymé
Tel : +33-1 56 53 81 37 Fax : +33-1 56 53 81 38
segolene.ayme@inserm.fr
Orphanet seeks editor for medical documentation/information
Job description
Edition of texts on rare diseases: identification of source documents required for editing and updating texts, interaction with medical experts and edition of short English-language texts.
Qualifications and experience
This post requires an individual with a strong scientific background, preferably with some medical knowledge. Biologists, medical doctors and pharmacists with editorial and information technology experience are welcome to apply for this position. Candidates should also be familiar with Microsoft Office (Word, Excel etc.) and with web-based search engines (PubMed etc.). A high level of English is essential: being a native English speaker (with a good understanding of written and spoken French) would be an advantage.
Contract
One-year contract, renewable for six years.
Salary
The salary will be awarded according to the public sector pay scheme and will depend on qualifications and experience.
Working hours
Flexible working hours (38.30 hours per week) with 47 days of annual leave.
Qualifications
University degree in the sciences or medical degree.
Employing institution
INSERM
101, Rue de Tolbiac
75654 PARIS Cedex 13
Location of the job
INSERM US 14
Rare Disease Platform
96 Rue Didot
75014 PARIS
Contact
ana.rath@inserm.fr
Two positions available working with the International Rare Disease Research Consortium
Two new positions are available with the International Rare Disease Research Consortium:
Job title: Project manager in the field of rare diseases and orphan drugs
Job description:
Management of a European project aiming at supporting the scientific secretariat of the IRDiRC (International Rare Disease Research Consortium). Direct management of a team of three other professionals. Organisation and planning of activities, organisation of an annual scientific congress and of several workshops. Administrative and financial management of the project. Reporting in English.
Team activity
Position at an INSERM service with forty professionals fully dedicated to database management, data collection and data publication in the field of rare diseases. The position is within a team of four people but requires interaction with other members of the service.
Qualification and experience
Solid background required in biology or medicine or pharmacy with experience in research. Good capacity to use information technologies. An experience in team and project management is also necessary, as well as good communication and interaction skills. Fluency in English is required.
Contract
One-year contract, renewable for six years.
Salary
Salary according to the scale of the public institutions in France, dependent on the diplomas and acquired experience in relevant position(s).
Working hours
38.30 per week and 47 days of vacation. Flexible hours.
Employing institution
INSERM
101, Rue de Tolbiac
75654 PARIS Cedex 13
Location of the job
INSERM US 14
Rare Disease Platform
96 Rue Didot
75014 PARIS
Contact:
Dr Ségolène Aymé
Tel : +33-1 56 53 81 37 Fax : +33-1 56 53 81 38
segolene.ayme@inserm.fr
Job title: Communication manager / science writer
Job description:
Communication manager of a European project aiming at supporting the scientific secretariat of the IRDiRC (International Rare Disease Research Consortium). Responsibility of the website. Communication exclusively in English.
Team activity
Position at an INSERM service with forty professionals fully dedicated to database management, data collection and data publication. The position is within a team of four people but requires interaction with other members of the service.
Qualification and experience
Background in biology or medicine or pharmacy with experience in research required. Good capacity to use information technologies. Good communication skills and capacity to simplify complex medical and scientific discoveries. Fluency in English is required.
Contract
One-year contract, renewable for six years.
Salary
Salary according to the scale of the public institutions in France, dependent on the diplomas and acquired experience in relevant position(s).
Working hours
38.30 per week and 47 days of vacation. Flexible hours.
Employing institution
INSERM
101, Rue de Tolbiac
75654 PARIS Cedex 13
Location of the job
INSERM US 14
Rare Disease Platform
96 Rue Didot
75014 PARIS
Contact:
Dr Ségolène Aymé
Tel : +33-1 56 53 81 37 Fax : +33-1 56 53 81 38
segolene.ayme@inserm.fr
The European Organisation for Rare Diseases (EURORDIS) seeks Director of Operations, Programmes and Projects
The European Organisation for Rare Diseases EURORDIS is recruiting a Director of Operations, Programmes and Projects. This is a new position within EURORDIS and will play a vital role in the support of programmes, projects, research and development as well as in working with EURORDIS members. The essential criteria for this position are: management skills, experience in the field of RDs, readiness to relocate to Paris and a fluency in English.
For further information
Courses & Educational Initiatives
Epidermolysis Bullosa – An Introduction and Advanced Management courses
Two training days devoted to Epidermolysis Bullosa are being held at the Great Ormond Street Hospital (London) in September 2012. The first, an Introductory Day, will be delivered by the EB Specialist Nurses at Great Ormond Street Hospital, and colleagues from St Thomas's Hospital. The programme will offer an overview of the different types of epidermolysis bullosa, (EB) multi disciplinary management and expected outcomes. It is suitable for community children’s nurses; nurses working in palliative care; and dermatology nurses. Learn more
The second day-long course, Advanced Management, will offer a greater understanding of the complexities and complications of EB and their management. It is geared towards medical practitioners working with adults and children with EB and will allow attendees to discuss the current research and current / potential therapies; recognise complications pertaining to the different types of EB; explain principles of general care of the patient with EB; describe current treatments and symptom management; and more. Learn more
Goldrain Courses in Clinical Cytogenetics and Prenatal Genetic Diagnosis
The Sixth Clinical Cytogenetics course will be held from 15-21 September 2012 at the Goldrain Castle in South Tyrol (Italy). The lectures are aimed at both clinicians and cytogeneticists who have strong mutual interests in both fields. To best profit from the lectures and exercises, participants should have at least one year of practical experience in laboratory and/or clinical cytogenetics.
The Goldrain Prenatal Genetic Diagnosis, tentatively course scheduled from 6-12 October 2012, is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination.
For further details
IberoAmerican Course for the Multidisciplinary Study of Movement Disorders: Parkinson Disease and Spinocerebellar Ataxias
This international workshop will held in Lima, Peru from 19-20 September 2012. The course is aimed at neurology residents and students in a doctoral degree program in medicine, biology, biochemistry, biotechnology, pharmacy, genetics, or related disciplines. This course will provide updates on the current knowledge in basic, clinical, and translational research, genetics, and therapeutics in movement disorders such as Parkinson disease and the Spinocerebellar Ataxias.
For further details
European Cytogeneticists Association Courses
The European Advanced Postgraduate Course in Classical and Molecular Cytogenetics is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. Information for the 2013 course is now available.
For further details
Online Master of Science in Haemoglobinopathy
A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy – such as counsellors, clinical psychologists, nurse specialists and midwives.
For further details
The European School of Haematology distance learning tools
The European School of Haematology (ESH) is a non-profit organisation founded in 1986. Its mission is continuous medical education in Haematology and the fields related to Haematology. ESH organises conferences throughout Europe and on other continents. It also produces distance learning tools of which many are freely available on the ESH website: These include: The Curriculum on Iron Metabolism and Related Disorders: This is a comprehensive curriculum comprising webcasted lectures, videos, interviews, round table discussions etc. The faculty is composed of distinguished international experts in the field. Webcasted conferences are also freely available on the website, including topics such as: Diagnosis and Management of Rare Anaemias; Haemoglobin Disorders: Laboratory Diagnosis and Clinical Management; World Cord Blood Congress, and more.
Orphan Academy 2012 Programme
The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
For further details
EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
For further details
What's on Where?
13th International Workshop on Multiple Endocrine Neoplasia
Date: 5-8 September 2012
Venue: Liege, Belgium
An established event for all those interested in research and treatment of multiple endocrine neoplasias, this workshop represents the ideal opportunity to share knowledge with peers and those working in related fields. Both research techniques and therapeutic modalities have undergone significant expansion in recent years and the program provides an opportunity for all to inform and be informed about thought-provoking advances in treatment, genetics and molecular biology.
For further details
The 13th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2012)
Date: 6-8 September 2012
Venue: Shanghai, China
Scientific sessions include: Beyond GWAS; Impact of 1,000 Genomes Project; Genome variation in complex diseases; Rare variations in neuropsychiatric and developmental disorders; New technologies; Challenges and Opportunities of large datasets; Therapeutic Targets Emerging from Genetic Variants in Common Networks; and much more.
For further details
First International Symposium on the Ehlers-Danlos Syndrome
Date: 8-11 September 2012
Venue: Ghent, Belgium
Topics include natural history; clinical aspects; updated nosology; diagnostics guidelines; therapeutic and management strategies; animal models, and more.
For further details
Joint DIA/ EFGCP/ EMA Medicines for Children Conference on Development of Paediatric Medicines: From Learning to Adapting
Date: 26-27 September 2012
Venue: London, UK
The aim of this conference is to discuss paediatric drug development in Europe, offering open discussion between academics, clinicians, regulatory authorities, patient associations and the pharmaceutical industry.
For further details
15th Biennial Meeting of the European Society for Immunodeficiencies
Date: 3-6 October 2012
Venue: Florence, Italy
The conference will cover the following topics: Inflammation; Immune Dysregulation; Innate Immunity; Hemophagocytic Lymphohistiocytosis; Immunotherapy; Networking for PID; Diagnostics of Combined Immunodeficiencies; Increasing Awareness of PID Worldwide; New Frontiers on PID Therapeutics; Gene Therapy; Autoimmunity in PID; New Developments in Transplantation; Mechanism of Humoral Dysregulation in PID; B Cell Disorders; Immunodeficiency Secondary to Autoantibodies: Phenocopies of PID; Thymus Defects; and DNA Repair and Telomere Defects. The XIIth Biennial Meeting of the International Patient Organisation for Primary Immunodeficiencies (IPOPI) is also being held in partnership with the European Society for Immune Deficiency (ESID), and the International Nurses Group for Immune Deficiency (INGID).
For further details
Mechanisms of Intellectual Disability: From Genes to Treatment
Date: 3-7 October 2012
Venue: Roscoff, France
The conference will cover the following topics: Genetics and Epigenetics of cognition and intellectual disorders; Cloning and characterization of genes; RNA metabolism and ID; Structures and plasticity of synapses and ID; Neurogenesis and synaptogenesis; Migration, interneurons and ID; Neuronal circuit development and ID ; and Towards a cure: lessons from animal models.
For further details
EpiRare International Workshop: Rare Disease and Orphan Drug Registries
Date: 8-9 October 2012
Venue: Rome, Italy
The International Workshop “Rare Diseases and Orphan Drug Registries” is organised in the framework of the EpiRare project (“European Platform for Rare Disease Registries”, co-funded by EU Commission, DG SANCO). Open to scientists, clinicians, patient associations, policy makers and enterprises, the workshop aims to share different experiences of rare disease registration in Europe and beyond; highlight the strengths and opportunities of linking rare disease registration activities, orphan drug post-marketing surveillance, etc; promote the sustainability and networking of registration activities; and more.
For further details
Second International Conference on Esophageal Atresia: From the Fetus to the Adult
Date: 8-9 October 2012
Venue: Montreal, Canada
In addition to bringing together experts from various disciplines, the theme of the conference will create important links between paediatric and adult medicine, reflecting the need for a continuum of care, which this increasingly numerous population requires. Inherent morbidity related to this condition also underlines the need for long-term monitoring.
For further details
Orphan Drugs & Rare Diseases Conference
Date: 8-9 October 2012
Venue: London, UK
This commercial event will present briefings from opinion leaders, including those with hands-on experience of regulating new drug discoveries, companies who have already developed advanced orphan drugs and been granted orphan designation, and selected experts in the field. Speakers will offer insights into expanding the reach of medicine to previously untreatable and unreachable patients with rare diseases; different regulatory and policy environments; new drug discoveries; innovative business strategies and funding models, and the importance of partnerships with patient groups and those at the point-of-care.
For further details
Days of Molecular Medicine 2012 Conference: The Translational Science of Rare Diseases - From Rare to Care
Date: 8-10 October 2012
Venue: Vienna, Austria
The conference brings together experts working on a broad spectrum of rare diseases to discuss new insights made possible by improved technologies such as next generation sequencing and the possibilities for translating these advances into new treatment approaches and therapies for patients.
For further details
15th Society for the Study of Behavioural Phenotypes International Research Symposium and Education Day: Social Phenotypes in Genetic Disorders
Date: 11-13 October 2012
Venue: Leuven, Belgium
The theme of this year's conference is "Social Phenotypes in Genetic Disorders" and the focus will be on the development, phenotype, genetics and brain basis of social cognitive skills, and on molecular targeted therapy in genetic syndromes.
For further details
FDA/EMA Orphan Product Designation and Grant Workshop
Date: 12 October 2012
Venue: Silver Spring, MD USA
The FDA Office of Orphan Products Development along with the European Medicines Agency (EMA) Orphan Medicines Section are holding this one-day workshop designed to provide valuable information about the EMA and FDA Orphan Drug Designation programs, the FDA Humanitarian Use Device (HUD) Designation program, the FDA Orphan Products Grant program, and European Union (EU) rare disease research programs to participants representing pharmaceutical, biotechnology, and device companies, as well as to academics. The workshop is being held in partnership with the European Organisation for Rare Diseases (EURORDIS), Genetic Alliance and the National Organization for Rare Disorders (NORD). There will be no registration fee for the workshop.
For further details
3rd Pan-European Conference on Haemglobinopathies and Rare Anaemias: Towards the Future
Date: 24–26 October 2012
Venue: Limassol, Cyprus
The Thalassaemia International Federation is delighted to announce the organisation of the 3rd Pan-European Conference, held under the auspices of the Cyprus Presidency and in close collaboration with the Cyprus Ministry of Health. The conference will bring together stakeholders to discuss avenues of action to tackle the growing public health burden of chronic and rare diseases in Member States and the EU.
For further details
The Second Joint International Symposium on Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation
Date: 26–27 October 2012
Venue: Ede, Netherlands
Topics will include autophagy; clinical studies; erythropoiesis; new genes; pathophysiology; protein-misfolding; treatment strategies and round table discussions with patient organisations and basic and clinical researchers.
For further details
41st European Society of Clinical Pharmacy Symposium: Personalised and Safe Therapy
Date: 29-31 October 2012
Venue: Barcelona, Spain
Featuring a session on Cross-border Healthcare and Rare Diseases. Other topics include Orphan drugs and ultra orphan drugs; European perspective of the clinical trials; Modeling and simulation in the development of new drugs by the pharmaceutical industry; Pharmacogenetics and pharmacists; Advances in personalized therapy in oncology; Approach to the polymedicated patient; Cost containment measures in hospital pharmacy services: the role of the hospital pharmacy services in the rational use of drugs, and more.
For further details
International Ataxia Research Conference
Date: 1-3 November 2012
Venue: London, UK
Topics will include emerging therapeutic strategies for the ataxias; genetic and molecular analysis of the frataxin gene and protein; episodic ataxias and non-inherited ataxias; ataxia clinical research from trials to clinic – biomarkers and clinical trials; and more. .
For further details
8th International Society for Newborn Screening European Regional Meeting
Date: 4-6 November 2012
Venue: Budapest, Hungary
Topics will include: To screen or not to screen - setting up screening panels; Congenital adrenal hyperplasia; Cystic fibrosis; Severe combined immune deficiencies; Lysosomal storage disorders; and more. .
For further details
6th International Symposium on Childhood MDS and Bone Marrow Failure syndromes
Date: 7-9 November 2012
Venue: Prague, Czech Republic
Topics will include Refractory Cytopenia of Childhood, advanced MDS; Juvenile Myelomonocytic Leukemia; Ph-negative Myeloproliferative Disorders; Therapy-related myeloid neoplasia; Severe Aplastic Anemia; Congenital Bone Marrow Failure; Morphology and Classification; Stem cell biology; Molecular aberrations and potential targets; Novel therapeutics, and Hematopoietic Stem Cell Transplantation.
For further details
3rd Annual World Orphan Drug Congress
29-30 November 2012
Geneva, Switzerland
The 3rd annual World Orphan Drug Congress provides a forum for the rare disease industry. This commercial event has three dedicated tracks this year: clinical development and R&D; market access, pricing, and reimbursement; corporate development and partnerships.
For further details
10th Asia-Pacific Conference on Human Genetics
Date: 5-8 December 2012
Venue: Kuala Lumpur, Malaysia
The APCHG2012 will examine various themes on personalised medicine, human variations in the Asia-Pacific region as well the latest advances on genetic diagnostics and technology and their implications to healthcare in the region. In addition, the APCHG2012 will also discuss issues pertaining to bioethics, genetics education and counselling as well as preventative strategies for birth defects and inborn errors of metabolism, and to provide a platform for patients and families to discuss emerging issues in individuals with inherited conditions and chronic disabilities.
For further details
7th Alstrom Syndrome International Family Conference and Scientific Symposium
Date: 9-13 May 2013
Venue: Massachusetts, USA
Medical professionals and scientists will hold Symposia on Thursday, 9 May and Saturday 11 May.
For further details
9th European Cytogenetics Conference
Date: 29 June - 02 July 2013
Venue: Dublin, Ireland
An opportunity for cytogeneticists to come together to discuss developments ranging from applications in prenatal or cancer diagnosis to chromosome biology in epigenetics and evolution.
For further details
8th International Prader-Willi Syndrome Conference
Date: 17-21 July 2013
Venue: Cambridge, UK
An opportunity for all involved worldwide in research, working or living with people with PWS to present current research and explore best practice in clinical and day to day management of PWS.
For further details
First International Primary Immunodeficiencies Congress (IPIC)
Date: 7-8 November 2013
Venue: Estoril, Portugal
The International Patient Organisation for Primary Immunodeficiencies (IPOPI) is delighted to announce the First International Primary Immunodeficiencies Congress (IPIC), a congress for all stakeholders with an interest in primary immunodeficiencies (PIDs). IPIC will provide a two-day programme focusing on clinical developments including PIDs pathogenesis, treatment, management of complications and more. Access to diagnosis and care, SCID newborn screening and other key world developments will also be addressed.
For further details