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The 2014 annual report on rare disease activities in Europe is now available

The annual report on the State of the Art of Rare Disease Activities in Europe is now available online. This extensive report, elaborated by the Scientific Secretariat of the EUCERD Joint Action, with the cooperation and input of the rare disease community, including Member State representatives of the EC Expert Group on Rare Diseases, provides a comprehensive overview of rare disease and orphan drug activities at both the European Union (EU) and Member State levels throughout 2013. The report includes EU Member States’ progress in developing and implementing a national plan/strategy for rare diseases, as recommended by the Council Recommendation on an Action in the Field of Rare Diseases.

By end 2013 - the deadline to elaborate national plans/strategies for rare diseases -, most EU Member States had submitted a plan/strategy to their national authorities. Sixteen countries have adopted a plan/strategy. France and Spain have implemented and assessed their first plan. As a top priority, most countries plan to identify and design centres of expertise for rare diseases. Many of these plans/strategies, however, have no dedicated budget for their actions, a result of the unfavourable economic context which may hinder the implementation of defined measures. The next challenge for EU Member States will be to implement and assess these plans, which the new Commission Expert Group on Rare Diseases will follow closely.

The year 2013 was not without highlights. The EUCERD completed its mandate with two new recommendations and one opinion adopted in 2013. Altogether, five recommendations and one opinion were adopted throughout EUCERD's mandate. A new EC Expert Group on Rare Diseases - replacing the EUCERD in January 2014 - will strive to reach its goals as successfully as the Committee did. Once again, Rare Disease Day was an acclaimed success in 2013, with 73 participating countries. The 2011 Cross-Border Healthcare Directive led to the 2014 publication of the Commission Delegated and Implementing Decisions concerning European Reference Networks.

The International Rare Disease Research Consortium (IRDiRC) constituted its Scientific Committees, ran the first IRDiRC conference in Dublin in April 2013 and published its policies and guidelines, all aimed to reach diagnosis of most rare diseases and 200 new therapies for rare diseases by 2020. Regarding orphan medicinal products, the EMA received 201 applications for Orphan Designation in 2013, the Committee on Orphan Medicinal Products adopted 136 positive opinions and the European Commission granted 136 orphan designations. Seven new orphan medicinal products received EU marketing authorisation in 2013.

The five-part report’s first volume provides an overview of rare disease activities in Europe. Additional individual country reports are available via the National resources link. These country reports provide up-to-date information concerning national activities on rare diseases. A synthesis of all 2013 activities is proposed in Part II: Key developments in the field of rare diseases in Europe in 2013. The report covers the following topics: 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. Bibliographies, web addresses organised by country and rare disease national plan/strategy document are provided in the report links. Over one hundred contributors supported this report update.

The six volumes of the report are freely accessible via the EUCERD Joint Action website.


EU Policy News
First Conference on European Reference Networks sheds light on the future of ERNs

At the invitation of the European Commission, a Conference on European Reference Networks (ERNs) was held on 23rd June 2014 in Brussels. The conference aimed to discuss the organisation of specialised networks across the EU and examine the next steps of the deployment process, in preparation of the forthcoming call for European Reference Networks in the fourth quarter of 2015.

The establishment of ERNs lays in accordance with Directive 2011/24/EU on patients' rights to cross-border healthcare. In the directive, along with low prevalence complex diseases or conditions, rare diseases are mentioned explicitly as an area in particular need of European clinical entity networks. Regardless of the region, the network must provide highly specialised, affordable, high-quality and cost-effective care.

The idea of linking centres of expertise throughout Europe in an effort to pool expertise and concentrate knowledge and resources is, of course, very attractive. The principles of such an approach were explored in depth by the Rare Disease Task Force and, subsequently, by the EU Committee of Experts on Rare Diseases (EUCERD) who published reports and recommendations.

The Member States and the European Commission began exploring the necessity of such networks in 2003, resulting in the publication of a Commission Delegated Decision and a Commission Implementing Decision on 10th March 2014. While the first document sets out criteria and conditions that ERNs and healthcare providers wishing to join ERNs must fulfil, the second document defines criteria to establish and evaluate ERNs and facilitate the exchange of information and expertise on establishing and evaluating such networks.

The conference gathered 340 participants from 29 countries who represented national public health authorities, as well as experts who coordinated past collaborative networks, financially supported by DG Research or DG Public Health, and patient organisation representatives. Participants expected to gain a clearer understanding of the type of ERN to propose in order to prepare for the first call in 2015.

The future ERNs will consist of networks of healthcare centres expected to collaborate without a specific allocated budget to support their networking activity. These networks will be quite different from the network models funded in the past in the field of rare diseases, which were networks between experts with allocated budgets to reach specific goals in research or public health. To date, no ERN of the new type exists, besides possibly networks in the field of cancer which benefit from funding through sources independent of the EC budget. The selected ERNs will have to support their budget through other sources to be identified.

The new ERNs are intended to network centres of expertise, but such centres will not necessarily be designated ones. Furthermore, while Member State health care authorities will be required to endorse and approve the selection of networks, they will not have given their prior consent at the stage of application for these networks. A further question concerns the scope of ERNs: should they be designed around one disease or around a large group of diseases? The Commission indicated that networks should include all diseases within a therapeutic area which may be difficult to reconcile with the very concept of highly specialised health care.


Sponsors to post clinical trial summary results in the European Clinical Trials Database
The EMA has announced that sponsors must begin posting clinical trial results in the European Clinical Trials Database (EudraCT) from 21st July 2014, once the final version of EudraCT is launched. Following the recent announcement of the new clinical trials regulation No 536/2014, and in accordance with the European Commission’s Guideline, Clinical Trials Directive 2001/20/EC and Paediatric Regulation to standardise clinical trials throughout the EU, sponsors will be legally required to upload clinical trial results to EudraCT within six or twelve months following trial completion, depending on the trial. Protocols and results information will become increasingly available for the public to access, download and save through the European Union Clinical Trials Register. Protocols and information from over 23,000 clinical trials registered in EudraCT are already available for public search in the register.

Read the EMA news release


National & International Policy Developments

The European Medicines Agency and US Food and Drug Administration propose joint clinical research on new medicines for Gaucher disease in children

The EMA and FDA released a draft joint proposal to facilitate clinical research on new medicines to treat Gaucher disease, a rare, inherited lysosomal storage disorder, in children. Based on extensive consultation with various stakeholders which began in October 2011, the proposal aims to reach an agreement on an EMA Paediatric Investigation Plan and FDA Pediatric Study Plan to conduct clinical investigation of treatments for children with Gaucher disease. While several drugs have been approved to treat patients with Gaucher disease, regulators consider treatments to be ill-adapted to paediatric patients. The treatment burden is considered to be particularly high in children with neurological symptoms. The EMA and FDA have therefore joined forces to develop a collaborative clinical research programme to demonstrate safety and efficacy of treatments and new routes of administration for paediatric Gaucher disease Type 1 and Type 3 patients.

Since recruitment of children in clinical trials is typically difficult for ethical reasons, the joint proposal suggests two complementary approaches. Sponsors can extrapolate data from adults for paediatric patients to avoid unnecessary clinical studies in children. The proposal also recommends conducting multi-arm and multi-sponsor trials in order to test larger numbers of investigational therapies simultaneously, thus keeping the number of children involved in trials as low as possible. Sponsors wishing to take part in this project are encouraged to seek advice from their regulatory authorities, as well as the EMA and FDA.

The document is available for public consultation and all comments should be sent in by 31 August 2014.

Read the EMA/FDA joint proposal

Proposal for international guidelines on conducting research and sharing genomic data
Sugano et al. published a proposed International Code of Conduct for Genomic and Health-Related Data Sharing in The HUGO Journal last month. Earlier this year, Knoppers et al. recommended, in an article published in Human Genetics, that a Code of Conduct be drawn up to promote data sharing within a human rights framework. OrphaNews reported on this last April. The latest draft of the Code was designed, under the aegis of the Global Alliance for Genomics and Health, by a consortium of research, patient advocacy, policy and bioethics communities including the Biobank Standardisation and Harmonisation for Research Excellence project (BioSHaRE), International Cancer Genome Consortium (ICGC), International Rare Disease Research Consortium (IRDiRC), International Society for Biological and Environmental Repositories (ISBER), Human Heredity and Health in Africa Initiative (H3Africa) and Public Population Project in Genomics and Society (P3G) among others.

Based on four founding principles regarding health, respect, research and transparency, the Code proposes guidelines to conduct research and share genomic data internationally with respect for human privacy and non-discrimination rights. Besides ethical values and the wish to avoid data misuse, the guidelines are designed to adapt to evolving genomic science and data sharing practices. The Code aims to establish a legal framework to be adopted by research organisations, institutions and industry conducting work using genomic and health-related data. In a spirit of wide collaboration, the authors of the Code invited anyone concerned to submit feedback on the draft until 1st July, before finalising the Code for implementation.

Read the Open Access article

Fostering orphan medicine research and development: The success of the FDA’s Orphan Products Grants Program
With support from the FDA’s Office of Orphan Products Development, the authors of an article published in Expert Opinion on Orphan Drugs studied the impact of the FDA’s Orphan Products Grants Program on the development of medicines and products for rare diseases. Since the Orphan Drug Act launch in 1983, US$320 million have been awarded to clinical studies on rare disease products. From an initial US$500,000 in 1983, funding has continued to rise, reaching US$12 million in 2013, a slight decrease from the US$14 to US$15 million allocated annually from 2005 to 2012.

The grant programme receives on average 90 to 100 applications a year. Though Imosili et al. note that applicants are US-based essentially, foreign public and private entities are also eligible to apply under an active Investigational New Drug application (IND) or Investigational Device Exemption (IDE). In fact, the programme funds a number of grants concerning multiple international sites.

Based on scientific and technical criteria, applications are reviewed and evaluated by an independent panel of experts. This independent review process avoids funding projects that are not regulatory sound or likely to meet market approval. Out of 567 awarded grants, the programme’s funds have contributed to the authorisation of 34 drugs, 9 biologics and 8 devices, representing around 10% of orphan products. Imosili et al. highlight that incentives such as the FDA’s grant programme are effective to foster research on rare diseases. Grants provide a significant source of funding for investigators with limited resources. While FDA’s Orphan Products Grants Program is one of the main programmes to fund rare disease clinical trials, others such as NIH’s Therapeutics for Rare and Neglected Diseases (TRND) programme and IRDiRC aim to accelerate the development of drugs and diagnostic tools for rare diseases.

Consult the abstract

New standardised protocols to conduct research on Congenital Muscular Dystrophy in mouse models
With the support of AFM Téléthon, Cure CMD and TREAT-NMD have developed a set of Standard Operating Procedures (SOPs) to study Congenital Muscular Dystrophy (CMD) in mouse models. Deficiency in the laminin alpha2 gene causes some of the most severe forms of muscular dystrophy. Laminin alpha2 deficient mice are therefore valuable models to conduct research and gain better knowledge of the underlying causes of CMD. Furthermore, disease-specific animal models offer the opportunity to study the efficacy of new treatments for neuromuscular diseases. However, while there is no shortage of data on animal models, standard protocols to conduct research are essential to compare data generated by different research groups. Led by Dr. Raffaella Willmann, a number of researchers have contributed towards developing standardised study procedures. Several SOPs describing step-by-step protocols to conduct research on neuromuscular diseases are now available.

Access the available animal model SOPs from TREAT-NMD or from Cure CMD.

If you wish to contribute to SOP development, please email Anne Rutkowski.

Beyond economic considerations: Health Technology Assessment for rare diseases should incorporate multiple criteria
In an editorial published in Expert Review of Pharmacoeconomics & Outcomes Research, Simoens defends the validity of Health Technology Assessment (HTA) using multi-criteria decision analysis to evaluate medicines and technologies for rare diseases. As he points out, HTA does in theory appear suitable to assess health products for rare diseases based on the European Network for Health Technology Assessment’s (EUnetHTA) definition of HTA: “Health technology assessment is a multidisciplinary process that summarises information about the medical, social, economic and ethical issues related to the use of a health technology in a systematic, transparent, unbiased, robust manner. Its aim is to inform the formulation of safe, effective health policies that are patient focused and seek to achieve best value.”

In practice however, HTA is often and almost exclusively based on the cost-effectiveness of orphan products. In an article published earlier this year in QJM, Hyry et al. argue that orphan drugs usually do not meet efficiency criteria under such conditions. Drummond et al. agree and add, in another article published recently in European Journal of Health Economics, that unless orphan drugs acquire ‘special’ status, policies to stimulate orphan drug development and policies to reimburse these medicines will continue to diverge. They suggest that increased collaboration between governments internationally, reflecting the global reach of pharmaceutical companies, might be part of the solution to reconcile these opposing policies. At a European level, EUnetHTA and EMA have in fact examined HTA policies in efforts to coordinate regulatory approval and reimbursement decisions. The outcome report of their joint initiative was announced last month and published in Value in Health. The EMA and EUnetHTA continue to investigate ways of addressing regulatory obstacles early on in efforts to improve medicines and orphan product evaluation, based on multi-stakeholder and multidisciplinary criteria.

Read the open access editorial

Other International News
Australia’s Life Saving Drugs Programme up for review
The Australian Minister for Health, Peter Dutton, announced last April that the Life Saving Drugs Programme (LSDP) post-market Review was to begin on 1st May. The LSDP aims to offer eligible patients access to subsidised drugs for serious and rare diseases. The LSDP Review, last conducted in 2009, will examine the programme over the next year to ensure that it still meets its objectives. Presently, ten orphan drugs are offered to rare disease patients through the LSDP to treat Gaucher disease, Fabry disease, Mucopolysaccharidosis, Pompe disease and Paroxysmal Nocturnal Haemoglobinuria.

Read the Department of Health’s announcement

Guidance Documents and Recommendations
Letter to the Editor: Urgent communication for medical staff caring for Ebola patients
Patients suffering from Ebola-virus or Marburg-virus hemorrhagic fevers often have deficiency in ionized serum calcium. Therefore calcium must be substituted in order to repair the coagulation defect.

Hemorrhagic diathesis in these cases is caused by the formation of gaps in the vascular endothelial layer. Ebola-virus infects macrophages/monocytic cells and these cells secrete cytokines which bind to endothelial cells. Endothelial gaps are caused directly by viral infection and indirectly by the cytokines released from infected macrophages.

Defects in the endothelial layer will result in a disseminated intravascular coagulation (DIC) with consumption of clotting factors including calcium and platelets. Clotting factors are also lost due to the permeability of the endothelial lining. This situation resembles the crust formation in a bleeding wound. The only difference is: in Ebola fever, a clotting defect is caused by consumption of clotting factors. The limiting factor in the virus induced hemorrhagic diathesis is calcium. This was demonstrated in 1971 by Egbring and Slenczka in guinea pigs infected with the Marburg virus. At day five of disease, these animals had <20% of the normal clotting factor and platelet values. In a thrombo-elastogramme, no coagulation was observed. However, when calcium was added with a final concentration of 0.01 or 0.02 M, coagulation was restored in a dose dependent way to ca. 50% of the normal values. It should be mentioned: this effect was achieved in an in vitro system containing less than 20% of clotting factors and platelets.

Meanwhile, Rollin, Bausch and Sanchez (J Infect Dis.; 196(Suppl.2):S364-71; 2007) demonstrated that patients suffering from Ebola Sudan hemorrhagic fever have an unfavourable prognosis when their level of calcium is < 6 mg/dL. From the above description, it follows that substitution of calcium as early as possible would help to save lives. Transfusion of blood or platelet concentrates cannot cure the hemorrhagic diathesis when patients are calcium deficient.

Prof. Dr. med. Werner Slenczka, Marburg, Germany, July 2014.

Microcytic anemias due to genetic disorders of iron metabolism or heme synthesis: practice guidelines
Consult the Pubmed abstract
To read more about "IRIDA syndrome"
To read more about "Hemochromatosis type 4"
To read more about "Aceruloplasminemia"
To read more about "Congenital atransferrinemia"
To read more about "Microcytic anemia with liver iron overload"
To read more about "Severe congenital hypochromic anemia with ringed sideroblasts"
To read more about "Autosomal recessive sideroblastic anemia"
To read more about "X-linked sideroblastic anemia with ataxia"
To read more about "X-linked sideroblastic anemia"
To read more about "Adult-onset autosomal recessive sideroblastic anemia"
To read more about "Erythropoietic protoporphyria"
To read more about "Congenital erythropoietic porphyria"

Blood ; 123(25):3873-3886 ; June 2014

Cystic fibrosis: practical guidelines for lung transplantation
Consult the Pubmed abstract
To read more about "Cystic fibrosis"

Pulm Med. ; 2014:621342 ; March 2014

Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline
Consult the Pubmed abstract
Hepatology ; 60(1):362-98 ; July 2014

Use of JAK inhibitors in the management of myelofibrosis: a revision of the British Committee for Standards in Haematology Guidelines 2012
Consult the Pubmed abstract
To read more about "Myelofibrosis with myeloid metaplasia"

Br J Haematol. ; [Epub ahead of print] ; June 2014

Acute hepatic porphyria: recommendations for diagnosis
Consult the Pubmed abstract
To read more about "Acute hepatic porphyria"

Eur J Intern Med. ; 25(6):497-505 ; July 2014

Bioinformatics, Registries and Data Management

Do-it-yourself patient registries: Proposed user-friendly design software
In an article published in Source Code for Biology and Medicine, Bellgard et al. propose new features for rare disease registry frameworks (RDRFs) that allow non-professional software developers to generate and manage patient registries. As the number of identified rare diseases grows, the need for dynamic registries has become increasingly important to manage the quantity of information and data. The ability to exchange information between registries is also essential to develop and optimise patient databases. Most registries, however, are still constructed on static programmes and data elements (DEs) requiring assistance from software developers. Exchanging information between registries therefore becomes complex and inefficient.

In efforts to standardise DEs to optimise registry use, update and aggregation, Bellgard et al. encourage the use of software that can be applied across different registries by all administrators. The authors propose constructing registries using several web framework programmes and open source database systems. The aim is to design dynamic and user-friendly patient registries that do not require additional software development or professional assistance. Python programming and MongoDB open-source document repository allow non-professional administrators to build efficient, dynamic and interrelated registries. Data coding programmes such as YAML also allow designers to import and export documents whenever necessary to complete information – such as patient consent – or share data with other research communities. Bellgard et al. believe these programmes and features to enhance RDRF design will improve data mining, sharing and re-use across registries, essential to conduct research and clinical trials on rare diseases.

Read the open access article

The dos and don’ts of designing patient registries: Learning from the European Cystic Fibrosis Society Patient Registry
An article published in Orphanet Journal of Rare Diseases describes mistakes to avoid when constituting and managing rare disease patient registries. Based on experience from the European Cystic Fibrosis Society Patient Registry (ECFSPR), the authors recommend key considerations to design an efficient registry. Researchers wishing to set up a registry must first collaborate with all data contributors and other registries in order to establish criteria on patient inclusion and the information to collect. Viviani et al. suggest defining an initially limited set of variables to test in a small patient population. At this early stage, adjustments are easily made. Subsequent variables should be added and tested gradually. This progressive approach to establish information criteria allows data collection to begin early, based on core criteria. The ECFSPR experience shows that attempting to analyse large data sets from different established patient registries, set up according to non-standard criteria, is burdensome and causes loss of information.

As research progresses and the knowledge on diseases evolves, Viviani et al. recommend that registries collaborate regularly on updating definitions to reflect new findings, improved technologies and disease understanding. The authors further suggest that peer reviewed published research contributes towards establishing universal criteria for disease definition and management. Resulting information collection criteria should be translated into standard operating procedures and multi-lingual documents to ensure data gathering and management standards are respected throughout registries for a rare disease. The authors further highlight the need to ensure registries are sustainable. Efficient management, national and international collaboration, quality of data and accreditation all contribute to attract funds to patient registries.

Read the open access article

Screening and Testing

Potential treatment for Duchenne Muscular Dystrophy: A strong argument for routine newborn screening
In her article published in Molecular Genetics and Metabolism, Pillers argues the case for systematic genetic screening of newborns and children at-risk of developing or carrying mutations for Duchenne Muscular Dystrophy (DMD). Belgium remains the only country to conduct systematic newborn screening and follow-up testing for DMD. Germany, Wales and Canada have abandoned DMD routine genetic testing and the US have never implemented newborn screening. The US Discretionary Advisory Committee on Heritable Disorders in Newborns and Children (DACHDNC) recommends screening for 57 disorders, among which DMD does not feature.

Pillers argues that past criteria for excluding DMD from routine screening , namely high rates of false positives and lack of treatment, no longer apply to the disease. The author highlights that growing progress in DMD genetic diagnosis and potential treatments must be considered. While ten years ago, no medical benefit resulted from newborn screening for DMD, today’s personalised therapeutic approaches show promise in slowing disease progression and, in some cases, reversing the underlying causes of DMD. Two drugs in late stage clinical development, Ataluren (PTC Therapeutics) and Drisapersen (Prosensa) demonstrate efficacy to increase dystrophin production - a key protein in muscle function - in DMD patients affected by several DMD gene mutations. The author therefore urges newborn screening committees to address the value of routine testing, enabling early disease management.

Consult the first page preview

Newborn screening for Fragile X is a delicate matter
In a further article published in JAMA Neurology, Tassone also supports newborn genetic screening for selected rare diseases and recommends including routine testing for Fragile X syndrome (FXS) in screening programmes. Again, early routine testing for FXS has not been adopted in the US due to past lack of screening accuracy and treatment. Diagnosis is conducted in suspected cases from 36 months of age only. Reproductive counselling and patient management are therefore delayed and inadequate. A recent large scale US newborn screening study demonstrates, however, that blood spot screening for FXS is reliable and feasible to detect FRM1 mutations before symptoms appear. Presymptomatic individuals could therefore benefit from early disease management and emerging targeted treatments.

While some individuals express full mutations in the FMR1 gene, others carry unstable premutations that could develop into full mutations in future generations. Though Tassone’s study demonstrates successful early detection of FMR1 full mutations, it also identifies these premutations and other unstable partial mutations. Such findings raise practical and ethical issues concerning carrier screening. Reproductive counselling may be offered to carrier parents, but Tassone recognises that repercussions of premutation detections on others family members could be difficult to assess. Nevertheless, the author maintains the importance of early screening to improve disease knowledge and, in view of recent therapeutic advances, address policy decisions regarding patient management.

Read the open access article
Read the letter to the author


EU Project Follow-up

First two candidates selected for EMA’s adaptive licensing pilot project
Following the launch of the EMA’s adaptive licensing pilot project last March, the agency has selected two products from the twenty applications received from companies. While the medicines have not been publicly revealed, the agency will contact the selected applicants in order to begin exploring potential adaptive licensing for these products. The EMA welcomes the rapid response and growing interest from companies to engage in the pilot project. The greater the numbers of projects, the more evidence regulators can gather to validate the adaptive licensing project.

As announced in OrphaNews last April, adaptive licensing aims to improve early access to new drugs for diseases with unmet medical needs. Data for benefit/risk assessment will be collected progressively to establish safety and efficacy of medicines, with a view to treat a wider patient population. Built on multi-stakeholder cooperation, the EMA’s adaptive licensing is a further effort to speed up the design of products and treatments based on concrete evidence.

Read the EMA news release


New Syndromes

Novel form of congenital lipodystrophy and fatty liver disease due to biallellic loss-of-function mutations in PCYT1A in two unrelated patients
The authors identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in PCYT1A. The phenotypic consequences include severe fatty liver and low HDL cholesterol levels. Both patients also had lipodystrophy, severe insulin resistance and diabetes.
Consult the Pubmed abstract

Proc Natl Acad Sci U S A ; 111(24):8901-6 ; June 2014
Early-onset autosomal recessive retinitis pigmentosa with macular coloboma is associated with a missense mutation in DHX38 in one consanguineous family
The authors described four individuals of a consanguineous Pakistani family affected by early-onset autosomal recessive retinitis pigmentosa with macular coloboma due to a missense mutation in DHX38.
Consult the Pubmed abstract

J Med Genet. ; 51(7):444-8 ; July 2014
Novel form of microcephaly with severe visual impairments, intellectual disability and short stature caused by a homozygous loss of DIAPH1 in a consanguineous family
The authors described a novel form of microcephaly with severe visual impairment, intellectual disability and short stature caused by a homozygous nonsense alteration in DIAPH1 in a multiply-affected consanguineous family.
Consult the Pubmed abstract

Eur J Hum Genet. ; [Epub ahead of print] ; April 2014
New type of mitochondrial disorder due to a defect in mitochondrial protein synthesis linked to a homozygous mutation in TRIT1 in one family
The authors identified a novel form of severe combined mitochondrial respiratory chain defects and corresponding perturbation in mitochondrial protein synthesis associated to a homozygous mutation in TRIT1 in one family.
Consult the Pubmed abstract

PLoS Genet. ; 10(6):e1004424 ; June 2014

New Genes

46,XY gonadal dysgenesis is associated with independent missense mutations in FOG2 in two patients
Consult the Pubmed abstract
To read more about "46,XY partial gonadal dysgenesis"

Hum Mol Genet. ; 23(14):3657-65 ; July 2014
Mild to moderate intellectual disability and epilepsy associated with a disruptive mutation in the X-linked KIF4A in four males from a single family
Consult the Pubmed abstract
J Med Genet. ; 51(7):487-94 ; July 2014
Microvillus inclusion disease caused by homozygous truncating mutations in STX3
Consult the Pubmed abstract
To read more about "Microvillus inclusion disease"

Gastroenterology ; 147(1):65-68.e10 ; July 2014
Sedaghatian-type spondylometaphyseal dysplasia linked to truncating mutations in GPX4 in two families
Consult the Pubmed abstract
To read more about "Spondylometaphyseal dysplasia, Sedaghatian type"

J Med Genet. ; 51(7):470-4 ; July 2014
Progressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in CLIC5 in a consanguineous Turkish family
Consult the Pubmed abstract
To read more about "Autosomal recessive non-syndromic sensorineural deafness type DFNB"

Eur J Hum Genet. ; [Epub ahead of print] ; April 2014
Autosomal dominant eccentric core disease due to a heterozygous mutation in the MYH7 gene in four affected family members over three generations
Consult the Pubmed abstract
To read more about "Central core disease"

J Neurol Neurosurg Psychiatry ; [Epub ahead of print] ; May 2014
MEND syndrome, a male-specific disorder characterized by digital abnormalities, intellectual disability and short stature, due to hypomorphic EBP mutations
Consult the Pubmed abstract
To read more about "Digital anomalies - intellectual disability - short stature"

Am J Med Genet A. ; 164(7):1642-7 ; July 2014
15q14 microdeletion syndrome is associated with haploinsufficiency of MEIS2 in four affected individuals from one family
Consult the Pubmed abstract
To read more about "15q14 microdeletion syndrome"

Am J Med Genet A. ; 164(7):1622-6 ; July 2014
Rodriguez syndrome due to a heterozygous de novo SF3B4 mutation in a long-surviving patient could be a severe form of Nager syndrome
Consult the Pubmed abstract
To read more about "Acrofacial dysostosis, Rodríguez type"

Am J Med Genet A. ; 164(7):1841-5 ; July 2014
Brachydactyly type E, non-dysmorphic facial features and normal intelligence caused by haploinsufficiency of HDAC4 in three individuals
Consult the Pubmed abstract
To read more about "Brachydactyly type E"

Am J Med Genet A. ; 164(7):1826-9 ; July 2014
Spectrum of diseases represented by somatic PIK3CA mutations: for the first time, these mutations are associated to the hemihyperplasia-multiple lipomatosis syndrome
Consult the Pubmed abstract
To read more about "Hemihyperplasia-multiple lipomatosis syndrome"

Am J Med Genet A. ; 164(7):1713-33 ; July 2014
Familial supravalvular aortic aneurysm is caused by the ELN gene triplication
Consult the Pubmed abstract
Cardiol Young. ; [Epub ahead of print] ; June 2014
Biphenotypic sinonasal sarcoma due to recurrent PAX3-MAML3 fusion
Consult the Pubmed abstract
Nat Genet. ; 46(7):666-8 ; July 2014
Ameloblastoma: identification of recurrent SMO and BRAF mutations
Consult the Pubmed abstract
To read more about "Ameloblastoma"

Nat Genet. ; 46(7):722-5 ; July 2014

Research in Action

Pericarditis: efficacy and safety of colchicine for treatment of multiple recurrences
Consult the Pubmed abstract
To read more about "Pericarditis"
To read more about "Idiopathic recurrent pericarditis"

Lancet ; 383(9936):2232-7 ; June 2014
Diffuse cutaneous systemic sclerosis: autologous hematopoietic stem cell transplantation increases mortality but confers a long-term event-free survival benefit
Consult the abstract
Consult this study on Orphanet

To read more about "Diffuse cutaneous systemic sclerosis"

JAMA ; 311(24):2490-2498 ; June 2014
Twin to twin transfusion syndrome: fetoscopic laser coagulation of the entire vascular equator reduces post-operative fetal morbidity
Consult the Pubmed abstract

To read more about "Twin to twin transfusion syndrome"

Lancet ; 383(9935):2144-51 ; June 2014
Uveal melanoma: selumetinib compared with chemotherapy results in mixed results
Consult the Pubmed abstract
To read more about "Uveal melanoma"

JAMA ; 311(23):2397-405 ; June 2014
Advanced biliary cancer: the addition of cetuximab to gemcitabine and oxaliplatin did not enhance the activity of chemotherapy
Consult the Pubmed abstract
To read more about "Cholangiocarcinoma"
To read more about "Carcinoma of the gallbladder"
To read more about "Carcinoma of the ampulla of Vater"

Lancet Oncol. ; 15(8):819-28 ; July 2014
Oesophageal cancer: gefitinib does not improve overall survival but has palliative benefits
Consult the Pubmed abstract
To read more about "Esophageal adenocarcinoma"
To read more about "Esophageal squamous cell carcinoma"

Lancet Oncol. ; 15(8):894-904 ; July 2014
Pancreatic carcinoma: adding GV1001 vaccination to chemotherapy does not improve overall survival
Consult the Pubmed abstract
To read more about "Pancreatic carcinoma"

Lancet Oncol. ; 15(8):829-40 ; July 2014
Patients with platinum-sensitive recurrent serous ovarian cancer with a BRCA mutation have the greatest likelihood of benefiting from olaparib treatment
Consult the Pubmed abstract
Lancet Oncol. ; 15(8):852-61 ; July 2014
MYH9-related disease: cochlear implantation is safe and effective in most patients with severe to profound deafness
Consult the Pubmed abstract
To read more about "MYH9-related disease"

Orphanet J Rare Dis. ; 9(1):100 ; June 2014
Immune thrombocytopenic purpura: eltrombopag and high-dose dexamethasone as frontline treatment
Consult the Pubmed abstract
To read more about "Immune thrombocytopenic purpura"

Blood ; 123(25):3906-8 ; June 2014
Immune thrombocytopenic purpura: avatrombopag, a thrombopoietin-receptor agonist, is well-tolerated and active
Consult the Pubmed abstract
To read more about "Immune thrombocytopenic purpura"

Blood ; 123(25):3887-94 ; June 2014
Steinert myotonic dystrophy: recommendation to advise women about the possibility of early decreasing ovarian function
Consult the Pubmed abstract
To read more about "Steinert myotonic dystrophy"

Reprod Biomed Online ; 29(1):94-101 ; July 2014
Interstitial 22q13 deletions not involving SHANK3 may contribute to cognitive and speech development and be involved in a new contiguous gene syndrome
Consult the Pubmed abstract
Am J Med Genet A. ; 164(7):1666-76 ; July 2014
Congenital pulmonary alveolar proteinosis in children on La Réunion Island could be a new inherited disorder
Consult the Pubmed abstract
To read more about "Congenital pulmonary alveolar proteinosis"

Orphanet J Rare Dis. ; 9:85 ; June 2014
Stem Cells

Duchenne muscular dystrophy: ex vivo gene editing of the dystrophin gene in muscle stem cells induced improvement in muscle morphology in a mouse model
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Stem Cells ; 32(7):1817-30 ; July 2014
Human umbilical cord blood-derived mesenchymal stem cells producing IL-15 eradicate established pancreatic tumor in syngeneic mice
Consult the Pubmed abstract
To read more about "Pancreatic tumor"

Mol Cancer Ther. ; [Epub ahead of print] ; June 2014
Gene Therapy
Catecholaminergic polymorphic ventricular tachycardia: AAV9 containing CASQ2 is able to cure the disease from birth to advanced age in knock-in mice
Consult the Pubmed abstract
To read more about "Catecholaminergic polymorphic ventricular tachycardia"

Circulation ; 129(25):2673-81 ; June 2014
Engineering adeno-associated viruses for clinical gene therapy: a review
Consult the Pubmed abstract
Nat Rev Genet. ; 15(7):445-51 ; July 2014
Therapeutic Approaches

Tauopathy: methylene blue improved behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice
Consult the Pubmed abstract
To read more about "Tauopathy"

Hum Mol Genet. ; 23(14):3716-32 ; July 2014
Beta-thalassemia: modified activin receptor IIB ligand trap mitigated ineffective erythropoiesis and reduced disease complications in a murine model
Consult the Pubmed abstract
To read more about "Beta-thalassemia"
To read more about "Beta-thalassemia intermedia"

Blood ; 123(25):3864-72 ; June 2014
Darier disease: miglustat, a pharmacological chaperone, restored mature adherens junctions and desmosome formation, and improved adhesion strength
Consult the Pubmed abstract
To read more about "Darier disease"

J Invest Dermatol. ; 134(7):1961-70 ; July 2014
Cold agglutinin disease: TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins
Consult the Pubmed abstract
To read more about "Cold agglutinin disease"

Blood ; 123(26):4015-22 ; June 2014
Nipah virus disease: African green monkeys treated with m102.4, a neutralizing human monoclonal antibody, survived infection
Consult the Pubmed abstract
To read more about "Nipah virus disease"

Sci Transl Med. ; 6(242):242ra82 ; June 2014
Pancreatic carcinoma: RG7787, a low-immunogenic anti-mesothelin immunotoxin, has high cytotoxic activity and gives durable tumor responses when combined with paclitaxel
Consult the Pubmed abstract
To read more about "Pancreatic carcinoma"

Mol Cancer Ther. ; [Epub ahead of print] ; June 2014
Biliary atresia: high-dose IgG therapy mitigates bile duct-targeted inflammation and obstruction in a mouse model
Consult the Pubmed abstract
To read more about "Biliary atresia"

Pediatr Res. ; 76(1):72-80 ; July 2014
Diagnostic Approaches

Inclusion body myositis: retrospective study identifying the principal pathological features useful in the diagnosis
Consult the Pubmed abstract
To read more about "Inclusion body myositis"

BMJ Open ; 4(4):e004552 ; April 2014

Patient Management and Therapy
Congenital heart malformation: birth during the early term period of 37 to 38 weeks’ gestation is associated with worse outcomes after neonatal cardiac surgery
Consult the Pubmed abstract
To read more about "Congenital heart malformation"

Circulation ; 129(24):2511-7 ; June 2014
Myelofibrosis with myeloid metaplasia: review on pacritinib, a JAK2/FLT3 inhibitor
Consult the abstract
To read more about "Myelofibrosis with myeloid metaplasia"

Expert Opinion on Orphan Drugs ; 2(7):725-733 ; July 2014
Peripheral T-cell lymphoma: evaluation of the treatment with mogamulizumab
Consult the abstract
Expert Opinion on Orphan Drugs ; 2(7):735-742 ; July 2014
Hereditary angioedema: review on icatibant
Consult the abstract
To read more about "Hereditary angioedema"

Expert Opinion on Orphan Drugs ; 2(7):743-750 ; July 2014
Cystic fibrosis: review on inhaled dry powder mannitol
Consult the abstract
To read more about "Cystic fibrosis"

Expert Opinion on Orphan Drugs ; 2(7):751-757 ; July 2014
Advanced renal cell carcinoma: review on pharmacotherapy options
Consult the abstract
Expert Opinion on Orphan Drugs ; 2(7):643-652 ; July 2014
Beta-thalassemia: an overview of current treatment strategies
Consult the abstract
To read more about "Beta-thalassemia"

Expert Opinion on Orphan Drugs ; 2(7):665-679 ; July 2014
Laron syndrome: review on emerging treatment options
Consult the abstract
To read more about "Laron syndrome"

Expert Opinion on Orphan Drugs ; 2(7):681-694 ; July 2014
Childhood autoimmune chronic uveitis: infliximab and adalimumab provide similar benefits and are superior to etanercept
Consult the Pubmed abstract
To read more about "Juvenile idiopathic arthritis"
To read more about "Behçet disease"
To read more about "Blau syndrome"

Arthritis Care Res (Hoboken) ; 66(7):1073-84 ; July 2014
Juvenile idiopathic arthritis: Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans
Consult the Pubmed abstract
To read more about "Juvenile idiopathic arthritis"

Arthritis Care Res (Hoboken) ; 66(7):1063-72 ; July 2014
Adrenal insufficiency: a review
Consult the Pubmed abstract
To read more about "Primary adrenal insufficiency"
To read more about "Cushing syndrome"
To read more about "Non-acquired combined pituitary hormone deficiency"

Lancet ; 383(9935):2152-67 ; June 2014
Cholangiocarcinoma: a review
Consult the Pubmed abstract
To read more about "Cholangiocarcinoma"

Lancet ; 383(9935):2168-79 ; June 2014
Myelodysplastic syndromes: a review
Consult the Pubmed abstract
To read more about "Myelodysplastic syndrome"

Lancet ; 383(9936):2239-52 ; June 2014
Schistosomiasis: a review
Consult the Pubmed abstract
To read more about "Schistosomiasis"

Lancet ; 383(9936):2253-64 ; June 2014
7 updated GeneReviews published
GeneReviews are expert-authored, peer-reviewed disease descriptions ("chapters") presented in a standardized format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions. 7 GeneReviews have been updated for:
Glycogen storage disease type V
Systemic primary carnitine deficiency
Adenosine deaminase deficiency
Familial Mediterranean fever
Greig cephalopolysyndactyly syndrome
Muenke syndrome
Pyridoxine dependent epilepsy


Orphan Drugs

Crowdfunding for orphan drug research and development: A little can go a long way
In an article published in Drug Discovery Today, authors Dragojlovic and Lynd examine the impact of crowdfunding - i.e. raising small amounts of capital from a large pool of donors through web-based tools - for research on rare diseases. Crowdfunding appears successful to support early-stage research into rare diseases. As pharmaceutical companies become increasingly risk-averse, fewer industry funds are allocated to early-stage investigations. The authors suggest that crowdfunding could bridge the gap between early proof-of-concept research, for which funding is difficult to obtain, and access to traditional grant competitions or industry funding.

Examples include the iCancer campaign to support research on neuroendocrine tumours (NET). The Indiegogo crowdfunding campaign created public awareness, attracting sufficient funds to reach its £2 (€2.5) million target within eight months. The Cure Black Bone Disease campaign, launched by Nicolas Sireau and the AKU Society, raised US$121,012 (€89,000) to support patients taking part in DevelopAKUre clinical trials on nitisinone to treat Alkaptonuria, also known as Black Bone Disease. Three further campaigns, Can anle138b delay the onset of genetic prion disease?, Kawasaki Disease Challenge and I Lowe you!, also illustrate the success of crowdfunding to raise funds to support research on rare diseases.

The authors suggest that, though crowdfunding appears to contribute to research on neglected rare diseases, campaigns require careful planning. To run a successful campaign, the authors encourage project leaders to seek support from foundations, advocacy groups or even celebrities to raise awareness. Some universities have set up fundraising programmes to sponsor university-based research. The question remains whether crowdfunding for rare disease research will continue to raise small amounts to finance early-stage research or whether not-for-profit funds might one day become a significant part of later-stage research and development.

Consult the PubMed abstract

Will Big Pharma turn orphan drugs into the new blockbusters?
Following the end of the drug blockbuster age, pharmaceutical companies increasingly turned their attention to the potential gains from orphan drug development. In an article published in Expert Opinion on Orphan Drugs, Stephens and Blazynski studied the trends in orphan drug development, based on Pharmaprojects data. Over the past thirty years, 657 orphan drugs were launched, representing 23% of products in development for rare diseases. The authors observe, however, that only a handful of rare diseases attracts industry attention, cancer being the leader with far more drugs in development than for other rare diseases.

The article reveals that companies increasingly investigate single drugs to target multiple rare diseases, thus increasing the chance for multiple indications and drug repositioning resulting in greater commercial gains. And while Big Pharma is turning its attention to rare disease markets, the authors suggest that companies follow general market trends in which even the orphan drug segment offers guaranteed returns, such as oncology. Rare diseases that are not sub-segments of well understood diseases or for which drug repurposing is not possible attract far less industry attention. The authors fear that economic downturn and governments’ reluctance to reimburse very expensive orphan drugs might further limit investment into orphan drug development for a great number of rare diseases.

Read the open source article

Regulatory News
EMA grants Kalydeco™ (ivacaftor) a positive opinion for eight additional indications in cystic fibrosis

The EMA’s Committee for Medicinal Products (CHMP) recommends the approval of Kalydeco™ (ivacaftor) to treat eight non-G551D gating mutations in cystic fibrosis patients, aged six and above. Kalydeco™ was first approved in Europe in July 2012 to treat patients with the G551D gating mutation. Indications now extend to some 250 patients in Europe affected by the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene. Based on Phase 3 clinical data, the CHMP’s positive opinion will be reviewed by the European Commission. The final decision on marketing approval will be announced within the next three to four months.

Read the CHMP opinion

FDA grants early marketing authorisation for Beleodaq™ (belinostat) to treat rare non-Hodgkin lymphoma
On 3rd July, Danish-based biopharmaceutical company Topotarget received FDA early marketing authorisation for Beleodaq™ (belinostat) under the agency’s accelerated approval programme. Beleodaq™ is approved to treat patients with relapsed or refractory peripheral T-cell lymphoma, a rare form of non-Hodgkin lymphoma (NHL). The drug is the third treatment for peripheral T-cell lymphoma approved since 2009 and its approval expands treatments options for patients.

Read the FDA news release



Call4proposals: Research Osteogenesis Imperfecta (OI)
The aim of this call is to (co-) fund projects that will generate better treatment of Osteogenesis Imperfecta.
Researchers from any country are invited to respond to this call. A wide range of treatment or research strategies will be considered. No area will be excluded as long as the quality of life of people with OI can be improved in a tangible and sustainable manner. All disciplines contributing to the well-being of people with OI are invited to join. Creation of alliances and partnerships across national boundaries and medical institutions are welcome. Application deadline: 1 August, 2014.
For further details

Care-for-Rare Science Award 2014
The Care-for-Rare Foundation at the Dr. von Haunerschen Children’s Hospital of the Ludwig-Maximilian University Munich is launching, for the second time, the Care-for-Rare Science Award 2014. The Care-for-Rare Research Award 2014 is endowed with €50,000 and should give young scientists the chance to initiate a basic or clinical research project in the field of rare diseases.
Application deadline: 15 August, 2014.
For further details

Ataxia research grants
The National Ataxia Foundation (NAF) is committed to funding the best science relevant to hereditary and sporadic types of ataxia in both basic and translational research. NAF invites research applications from U.S.A. and International non-profit and for-profit institutions. One-year seed money grants of up to $15,000, and promising proposals up to a maximum of $30,000, will be considered for early or pilot phases of studies and ongoing investigations.
Deadline for letter of intent (half- to one-page abstract with specific research aims): 15 August, 2014.
Deadline for full application: 15 September, 2014.
For further details

Fondation Jérôme Lejeune Grants
The Scientific Advisory Board of the Jérôme Lejeune Foundation invites researchers investigating genetic intellectual disability to submit their projects on treatment identification to improve cognitive deficits of patients, especially those with trisomy 21 (Down syndrome) and other rare abnormalities such as fragile X, cri du chat, Rett, Williams-Beuren, Prader-Willi, Angelman, and other syndromes, excluding autism.
Jérôme Lejeune Foundation will provide a special consideration to projects leading to a better understanding of the mechanisms of accelerated brain aging associated with trisomy 21.
Grants are offered for one or two years. Funding is around €20,000 per year.
The Scientific Advisory Board reviews applications twice a year (November and December).
Application deadline for the second funding cycle: 19 August, 2014.
For further details

The Sturge-Weber Foundation Research Grants
The Foundation strives to stimulate and support research on all aspects of Sturge-Weber syndrome, Klippel-Trenaunay, and Port Wine Stain related conditions.
Young Investigator Awards: up to US$ 30,000 per year for maximum of two years in postdoctoral fellowship support (salary stipend and conference allowance) to encourage the brightest young minds to enter the field. Applicants must be no more than four years out of M.D. or Ph.D. programme and work under the supervision of an established mentor.
Pilot Research Studies: up to US$30,000 per year for maximum of two years for innovative studies with the potential for continued support from federal or other agencies. These awards are available to investigators at any stage in their career. Applicants from accredited medical schools and universities will be considered. The award will be made to the institution where the investigator will conduct his/her work and will not pay indirect costs.
Deadline for letter of intent summarising the proposed project: 1 September, 2014.
Application deadline: 15 December, 2014.
For further details

Myotonic Dystrophy Foundation (MDF) Fund-a-Fellow postdoctoral grant programme
The Fund-a-Fellow programme supports MDF's commitment to care and a cure for myotonic dystrophy (DM) by attracting new researchers to the field of DM research and increasing the knowledge and science available regarding myotonic dystrophy. In 2013 MDF expanded the list of scientific research endeavours eligible for fellowship support, including DM research efforts focused on improving care, treatment and support of the DM patient and the patient's family, as well as research focused on molecular biology and basic science.
MDF Fund-a-Fellow grants are US$100,000 each, disbursed over two years, and are awarded to post-doctoral students who have received doctoral degrees from accredited US or international institutions within the past three years.
Application deadline: 5 September, 2014.
For further details

DEBRA International research grants
Epidermolysis Bullosa (EB) is a group of rare genetic skin conditions, characterised by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. This grant aims to:
  • Improve the understanding of the biology and genetics of all forms of EB, as better understanding can lead to new approaches to diagnose and treat EB;
  • Work towards the development of therapies (including possible gene-therapies, cell-therapies, drug therapies or protein therapies);
  • Understand the nature of wound healing and the development of skin cancer in EB, and seek to develop better treatments and prevention strategies;
  • Support clinical care research to improve the management of EB through symptom relief.
  • Application deadlines: 15 February or March and 15 September, 2014.
    Decisions on funding applications from these calls will normally be made in June and December, respectively.
    However, details of calls and submission dates vary from one year to another, so keep checking this page

    NBIA Disorders Association Announces Research Grants for Pantothenate Kinase-Associated Neurodegeneration (PKAN)
    The NBIA Disorders Association is accepting applications for one-year grants for clinical and translational research studies related to the early detection, diagnosis, or treatment of patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN), the most common of the NBIA disorders. NBIA is a group of rare, genetic, neurological disorders characterised by the accumulation of iron deposits in the brain and progressive degeneration of the nervous system.
    The grant programme aims to encourage meritorious research studies designed to improve the diagnosis or treatment of NBIA. Research can be conducted in the US, EU, Canada, Australia, New Zealand, Brazil, Argentina, Chile, South Africa, Japan, or Israel, and in other countries where adequate supervision of grant administration is possible.
    Application deadline: 15 September, 2014.
    For further details

    FRT - Fondation René Touraine (FRT) Award
    These grants are awarded to encourage exchanges and international collaboration between research laboratories or clinical departments for pre- or post-doctoral research fellows and dermatologists. The award consists of one €18,000 fellowship for a long-term exchange and four €4,500 fellowships for a short-term exchanges. Eligibility criteria for these grants includes: exchange with a laboratory or department from another country; involvement of at least one European laboratory; benefits for both host and home laboratories.
    Application deadline: 1 October, 2014.
    Download the application form
    For further details


    Partnersearch, Job Opportunities
    Telethon Italy call for two career award positions
    The mission of the Fondazione Telethon is to advance excellent research in Italy towards a cure for human genetic diseases. To this aim, Telethon funds Career Awards for outstanding scientists wishing to establish their independent laboratory in a public or private non-profit Italian research institution.
    Three position levels are under consideration: Assistant (entry level), Associate and Senior Telethon Scientist.
    In the present Call, two Assistant Telethon Scientist positions are open. Awards will depend on availability of funds.
    The successful candidates will join the Dulbecco Telethon Institute (DTI), a virtual institute whose members are given the title of “Telethon Scientists”. These talented scientists work on a broad range of topics and in different Italian Institutions but share the same principles of rigour and excellence in the pursuit of scientific research aimed at understanding, preventing and curing genetic diseases.
    Application deadline: 18 July, 2014.
    Calls for application


    Courses & Educational Initiatives

    EUPATI Training Course
    The EUPATI Expert Training Course is an opportunity offering patient advocates expert-level training in medical research and development, specifically tailored for them. The certificate course will be a mixture of online and face-to-face modules over a 13-month period, beginning in September 2014.
    For further information

    INTERNATIONAL SUMMER SCHOOL: Rare diseases and orphan drug registries
    Date: 15-19 September, 2014
    Venue: Rome, Italy

    The School will take the participants through the main concepts and methodological steps that must be undertaken in the establishment and management of a rare disease registry and to ensure its usefulness, scientific soundness and sustainability.
    For further information

    ‘EXPLIQUE-MOI LES ESSAIS CLINIQUES’: The keys to understanding clinical trials to become an actor of one’s disease (in French)
    Date: 14-15 October 2014
    Venue: Marseille, France

    The objective of this course is to sensitise patients to clinical trials through better understanding of the drug development process, in particular the way in which clinical trials are conducted.
    The course will be held in French.
    For further information

    III INTERNATIONAL EPIRARE WORKSHOP: Rare disease and orphan drug registries
    Date: 24-25 November, 2014
    Venue: Rome, Italy

    Participants will be able to exchange experiences and present scientific results, in an effort to foster international collaboration.
    For further information

    Quality assessment of health care guidelines for rare diseases
    Date: 26-27 January, 2015
    Venue: Rome, Italy

    Target: Health professionals
    For further information

    Health care guidelines for rare diseases
    Date: 28 January, 2015
    Venue: Rome, Italy

    Target: Rare disease patients and their caregivers, patient representatives
    For further information


    What's on Where?

    Disorders of the Corpus Callosum Conference
    Date: 18-20 July, 2014
    Venue: Massachusetts, US

    Featuring 35 informative lectures and discussion groups, the conference's professional presentations are grouped into five tracks under the headings of Medical, Therapies, Behaviours, Education, and Financial/Community Life. Panel question and answers discussions will be held on the medical, genetic and behavioural aspects of disorders of the corpus callosum. Adults over 18 years, diagnosed with a DCC, are invited to participate in discussion groups and life-skills workshops.
    For further information

    Ehlers-Danlos Conference 2014
    Date: 18-20 July, 2014
    Venue: Parramatta, Australia

    The conference will cover topics that affect children, adolescents and adults with Ehlers-Danlos Syndrome, offering a comprehensive programme with local and international experts.
    For further information

    Third Symposium ATP1A3 in disease: Genotype/phenotype correlations, modelling and identification of potential targets for treatment
    Date: 29-31 August, 2014
    Venue: Lunteren, The Netherlands

    Pathogenic ATP1A3 mutations causing Alternating Hemiplegia of Childhood, rapid-onset dystonia-parkinsonism, and CAPOS syndrome will be discussed at the level of genetics, medicine, physiology and biochemistry. Participants of this conference are patient families, physicians and scientists from academia and indutry.
    For further information

    3rd Nordic Conference on Rare Diseases
    Date: 4-5 September, 2014
    Venue: Helsinki, Finland

    NCRD 2014 will be the 3rd Nordic conference focusing on the rare diseases and current topics related to them. NCRD 2014 will introduce national plans and strategies for rare diseases in Nordic countries, implementation of the plans and experience gained so far. The conference offers an excellent opportunity to network and to support the exchange of best practices throughout Nordic countries. Joint action will further help patients and professionals share expertise and information across borders.
    For further information

    25th European Dysmorphology Meeting
    Date: 10-12 September, 2014
    Venue: Strasbourg, France

    The aim of this meeting is to bring young clinical geneticists and trained dysmorphologists together to share their professional experience and present their clinical challenges. EuroDysmorpho is open to any presentation in the field of human development. Illustrative case reports are equally welcome. The meeting offers ample opportunities for exchanges and discussion. Everyone coming to the meeting is committed to present a communication and/or an “unknown” case report.
    For further information

    EFGCP Multi-Stakeholder Workshop & Discussion: How to Ensure Optimal Ethical Review within the New Clinical Trials Regulation?
    Date: 11 September, 2014
    Venue: Brussels, Belgium

    This workshop aims to facilitate an exchange of opinions on opportunities and threats of the new Clinical Trial Authorisation (CTA) assessment requirements for the ethical review. It will also be an opportunity for early feedback from some Member States on potential concepts and options for the successful collaboration between ethics committees and competent authorities. This event will benefit commercial and non-commercial sponsors, as well as patients who are eagerly waiting to participate in Clinical Trials and benefit from new treatment options.
    For further information

    15th International Conference on Human Genome Variation and Complex Genome Analysis (HGV2014)
    Date: 17-19 September, 2014
    Venue: Belfast, Ireland

    Around 100 delegates and 25 internationally recognised speakers will discuss, in a workshop-style atmosphere, latest progress on next generation sequencing, epigenomic variation, population studies, stratified and personalised medicine, data and knowledge sharing, biomedical informatics, genomic evolution, genomic technology advances, and human mosaicism and aging.
    For further information

    International Clinical Conference Jérôme Lejeune: Intellectual disability and the importance of assessment
    Date: 18-19 September, 2014
    Venue: Paris, France

    Renowned leaders from around the world will present their cutting-edge research on assessment and how it can contribute to improving our understanding of the different genetic conditions associated with intellectual disability, improve our evaluation of individual functioning, personalise our delivery of supports and services, and measure intervention effectiveness. The conference programme was developed for an audience of clinicians who provide care or supports to persons with intellectual disability and their families.
    For further information

    SIOPE – ENCCA Conference 2014: Joining Efforts for a Brighter Future for Children and Adolescents with Cancer
    Date: 18-19 September, 2014
    Venue: Brussels, Belgium

    The conference will address: Integrating innovative therapies into standard care; Improving quality of life in survivors; Solving inequalities across Europe; and Mobilising all stakeholders.
    EU and national policy makers, parents, patients, health professionals, researchers, regulators, charities and international bodies are welcome.
    For further information

    16th International Conference on Behçet’s Disease
    Date: 18-20 September, 2014
    Venue: Paris, France

    This conference will provide high quality contributions on a wide range of topics including clinical innovations, genetics and basic science. Updates on new therapeutic strategies will be presented and challenging issues will be discussed. Distinguished lecturers in the field of innate immunity are expected to participate in panel discussions.
    For further information

    2nd European Conference on Aniridia
    Date: 19-20 September, 2014
    Venue: Venice, Italy

    Aniridia Europe and Aniridia Italiana are pleased to announce the 2nd European conference on Aniridia. Their aim is to improve information and treatment of aniridia, foster research by creating scientific interest, connect professionals at local and international levels, develop guidelines, and support patients. Aniridia is a rare genetic disorder affecting vision, characterised by incomplete formation of the iris.
    For further information

    4th Annual Brain Metastases Research and Emerging Therapy Conference
    Date: 19-20 September, 2014
    Venue: Marseille, France

    This European Organisation for Research and Treatment of Cancer (EORTC) initiative intends to foster a multidisciplinary approach needed to develop brain metastases (BM) projects across several tumour types and disciplines such as breast cancer, lung cancer, melanoma, imaging, pathobiology and radiation oncology. This conference aims to stimulate innovative and insightful research in a collaborative environment and improve the standard of care and methodology of clinical research. Topics will cover new models of Academia-Industry partnership and biobanking strategies in BM to enhance personalised medicine approaches.
    For further information

    9th International Research Symposium on Marfan Syndrome and related disorders
    Date: 25-27 September, 2014
    Venue: Paris, France

    The International Symposia are state-of-the-art meetings on Marfan syndrome and related disorders at which new cutting-edge research is presented and discussed. Efforts have been made to integrate both basic and translational mouse studies with clinical studies in each session. This is done to encourage discussion between clinicians and researchers so all can better understand the value and limitations of translational mouse model studies.
    Session topics include presentations on current clinical trials, controversial surgical issues and techniques, challenging issues in non-cardiovascular aspects of Marfan syndrome, clinical management of new related disorders, phenotype/genotype correlations, pathogenic mechanisms in animal models, and emerging therapeutic strategies.
    For further information

    3rd International Conference on Immune Tolerance 2014
    Date: 28-30 September, 2014
    Venue: Amsterdam, The Netherlands

    The Third International Conference on Immune Tolerance will bring together international delegates to share their latest research and insights into the mechanisms and treatment of many conditions, most notably in transplantation, autoimmune diseases, inflammation and cancer.
    For further information

    EFGCP / DIA / EMA Annual Conference 2014 on Better Medicines for Children: ‘Explore Ways to Enhance Collaboration Between Key Players’
    Date: 30 September - 1 October, 2014
    Venue: London, UK

    The programme will soon be published on EFGCP website.
    Keep checking here for upcoming information

    Single topic symposium in metabolic liver disease
    Date: 2-4 October, 2014
    Venue: Birmingham, UK

    This symposium will include experts presenting information on diagnosis and treatment of metabolic liver disease as well as information on lipid disorders such as homozygous hypercholesterolaemia, Lysosomal acid lipase deficiency, Mitochondrial Diseases and other specific metabolic disorders.
    For further information

    ICORD 2014 Annual Meeting: Societal value of Prevention, Diagnosis and Treatment of Rare Diseases
    Date: 7-9 October, 2014
    Venue: Ede, The Netherlands

    The ICORD annual meeting will take place in conjunction with the FIGON Dutch Medicine Days and interactive sessions with ZonMw, the Dutch Drug Evaluation Board and the Dutch Clinical Trial Foundation will be organised in addition to separate ICORD sessions. The conference will cover a wide range of medical, investigational, political, social, industrial and economical topics. Sessions will include: Prevention, diagnosis and neonatal screening, Orphan drugs and personalised medicine, Patient views of the societal value, Registries and biobanks, and Worldwide collaborations. In addition to plenary sessions, the ICORD working groups, open to all, will further discuss regulatory business, research and patient organisations.
    For further information

    The Translational Science of Rare Diseases: From Rare to Care II
    Date: 8-10 October, 2014
    Venue: Herrenchiemsee, Germany

    This meeting will bring together high-profile scientists from around the world, active in the field of rare disease research and translational medicine, and will focus on how basic science on rare diseases can have an impact for the development of novel therapeutic strategies.
    For further information

    9th ISNS European Neonatal Screening Regional Meeting
    Date: 12-15 October, 2014
    Venue: Birmingham, UK

    This conference will focus on neonatal screening for various diseases.
    For further information

    Dysmorphology and Radiology of Inborn Errors of Metabolism
    Date: 16-17 October, 2014
    Venue: Manchester, UK

    The topics covered will be of interest to clinicians who deal with rare disorders or have an interest in clinical genetics, IEMs or paediatrics. Participants are expected to have some background knowledge of the field, although extensive experience is not required. Participants are strongly recommended to bring interesting, unusual or unsolved cases for discussion.
    For further information

    International Scientific Symposium on Angelman Syndrome 2014
    Date: 17-19 October, 2014
    Venue: Paris, France

    Organised by the French Angelman Syndrome Association (AFSA), the symposium will bring together international scientists studying the mechanisms associated with Angelman syndrome and promote exchanges between researchers to advance research in genetics and neuroscience on this rare disease. The meeting is open to official representatives of European and national Angelman syndrome organisations (up to 2 persons per organisation).
    For further information

    64th Annual Meeting of the American Society of Human Genetics: ASHG 2014
    Date: 18-22 October, 2014
    Venue: San Diego, US

    The ASHG Annual Meeting is the largest human genetics meeting and exposition in the world. This year’s meeting is expected to attract over 6,500 scientific attendees and over 200 exhibiting companies. ASHG members and leading scientists from around the world are selected to present their research findings at invited, platform, and poster sessions. Abstracts of work submitted for presentation at the Annual Meeting are published online and are citable. ASHG's Annual Meeting also features a trade show floor that offers attendees the opportunity to view state-of-the-art medical and laboratory equipment, products, services, and computer software designed to enhance human genetics research, teaching, and consultation.
    For further information

    NORD’s Rare Diseases and Orphan Products Breakthrough Summit
    Date: 22-23 October, 2014
    Venue: Alexandria, Virginia, US

    The 2014 Breakthrough Summit will concentrate on innovative content and will welcome the top leaders from the FDA, NIH, Industry, Patient Groups, Payers and Research Institutions to address the progress of rare disease diagnosis, genomics, drug development, patient engagement, product approvals, FDA oversight and market accessibility to orphan products.
    For further information

    14th International Congress on Neuronal Ceroid Lipofuscinoses (Batten Disease)
    Date: 22-25 October, 2014
    Venue: Córdoba, Argentina

    Batten disease is a common name for a group of rare, neurodegenerative genetic disorder affecting approximately 1 in 30,000 individuals. This conference will bring together experts on the latest research into Batten disease, experimental therapies, and clinical perspectives. Workshops will also be organised, covering topics such as patient registries and ethical issues.
    For further information

    International VHL Medical Symposium
    Date: 23-25 October, 2014
    Venue: Madrid, Spain

    Biennial International VHL Medical Symposia bring together the leaders in VHL basic, translational and clinical research, as well as the leading clinicians in clinical treatment for VHL. The gathering creates a stimulating environment while helping to make connections among these professionals that will spur the pace of progress in understanding and treating VHL. The content is aimed at medical researchers and healthcare professionals. Patients and caregivers are encouraged to attend. Their participation is highly valued as they are the true authorities of von Hippel-Lindau.
    For further information

    30th Annual Meeting of the Histiocyte Society
    Date: 28-30 October, 2014
    Venue: Toronto, Canada

    The Annual Meeting of the Histiocyte Society serves as the main forum for many of the world's most accomplished histiocytosis researchers and medical professionals to engage in vital collaboration and dialogue with one another. This year, the Society's 30th Annual Meeting will feature presentations on the study and treatment of the histiocytic disorders. Society members will present updates on ongoing Society-sponsored clinical trials on the histiocytic disorders.
    For further information

    ESID Meeting 2014
    Date: 29 October - 1 November, 2014
    Venue: Prague, Czech Republic

    The 16th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2014), offers access to the latest research and analysis in the field. Meeting participants will gain insights into innovative perspectives in both basic and clinical research. The scientific programme will draw together experts from around the world to discuss breakthroughs in diagnostic immunology, genetics and immunobiology of human diseases, advances in clinical practice, novel therapeutic approaches to tolerance induction and new insights into stem-cell and cellular therapies.
    For further information

    New frontiers in Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation: From Benchside to Bedside
    Date: 30 October - 1 November, 2014
    Venue: Stresa, Italy

    This third joint symposium on Neuroacanthocytosis addresses neurologists, interns, haematologists and biotechnologists working in the field of diagnostic, clinical and therapeutic management of patients affected by Neuroacanthocytosis and brain iron accumulation diseases. The scientific issues of this meeting will cover both the identification and characterisation of new aspects of this condition, as well as clinical developments.
    The international NBIA umbrella patient organisation NBIA Alliance offers travel grants for postdoctoral fellows and early career clinical doctors, involved in NBIA research and interested to attend the 3rd Joint NA & NBIA Symposium.
    For further information

    2nd International Rare Diseases Research Consortium (IRDiRC) Conference
    Date: 7-9 November, 2014
    Venue: Shenzhen, China

    The second conference is organised by the International Rare Diseases Research Consortium (IRDiRC), in collaboration with the BGI. The conference will gather top scientists from Europe, North America and Asia-Pacific for dynamic exchanges on knowledge and expertise. The event will also include an educational track. The ambition of this conference is to provide researchers with opportunities to establish new collaborations and confront different cultural approaches to the challenges posed by rare diseases.
    For further information

    Ataxia Telangiectasia Clinical Research Conference 2014
    Date: 13-15 November, 2014
    Venue: Nijmegen, The Netherlands

    The bi-annual A-T Clinical Research Conference 2014 brings together leading figures from the fields of clinical science and translational research in Ataxia-Telangiectasia. The objective of the conference is to share knowledge and map progress in the fields of current research and help identify priorities for future research and opportunities for collaboration. The programme includes lectures, presentation of selected abstracts, a poster session, four workshops, a ‘best poster prize’ and a social programme.
    For further information

    Cilia 2014
    Date: 18-21 November, 2014
    Venue: Paris, France

    Cilia 2014 will focus on (but not be limited to) recent advances in cilia structure and function, including trafficking, cilia and development, cilia in human genetic disease and cilia in infectious microorganisms. The event is organised by four European cilia networks: GDR CIL (France), the Ciliopathy Alliance, the Nordic Cilia & Centrosome Network (Scandinavia) and the EU-FP7 SYSCILIA programme.
    For further information

    22nd René Touraine Foundation for Dermatology Scientific Meeting
    Date: 5 December, 2014
    Venue: Paris, France
    Every year, the Scientific Meetings go over any acquired knowledge on one skin cell. Mornings are reserved for fundamental approaches, while afternoons are devoted to approaches applied to physiopathology, pharmacology and therapeutic. These are multi-subject meetings. Each presentation starts with a general overview of the terminology used, and continues with the speaker’s own research.
    For further information

    2nd International Primary Immunodeficiencies Congress (IPIC)
    Date: 5-6 November, 2015
    Venue: Budapest, Hungary

    The International Patient Organisation for Primary Immunodeficiencies (IPOPI) announces the Second International Primary Immunodeficiencies Congress (IPIC). This event will build on the successful outcomes of the first IPIC, attended by 400 participants. The congress will consist of a two-day programme and is open to all stakeholders with an interest in clinical management of primary immunodeficiencies (PIDs).
    For further information

    13th International Congress of Human Genetics (ICHG) 2016
    Date: 3-7 April, 2016
    Venue: Kyoto, Japan

    Hosted by the East-Asian Union of Human Genetic Societies (EAUHGS) and the Japan Society of Human Genetics, the 13th ICHG will focus on progress in genome analysis technologies and big data in order to explore disease mechanisms and treatment opportunities.
    Registrations open in 2015.
    For further information


    Commercial events

    Orphan Drugs Summit 2014
    Date: 17-19 September, 2014
    Venue: Copenhagen, Denmark

    A well-established platform where pharmaceutical companies of all sizes, hospital representatives, researchers, patient organizations, venture capitalists, regulatory bodies, and industry associations meet to discuss and influence the future of orphan drugs. The Summit is designed to increase interaction among participants, promote knowledge flow and instigate partnerships and alliances for those working with orphan drugs.
    For further information

    Orphan Drugs and Rare Diseases
    Date: 20-21 October, 2014
    Venue: London, UK

    SMi present the 3rd Annual Orphan Drugs and Rare Diseases Conference. The Orphan Drugs market is set to rise as a result of pharmaceutical companies now looking to orphan drugs as an essential revenue stream with 2014 set to be the year to see Orphan adoption.
    For further information

    3rd annual World Biosimilar Congress
    Date: 11-12 November, 2014
    Venue: Geneva, Switzerland

    The 3rd annual World Biosimilar Congress offers keynotes, case studies and roundtables covering topics relating to process, production, regulation and marketing strategies for biosimilars. Speakers and attendees include industry executives, middle managers, academics, key influencers and end-users.
    For further information

    The World Orphan Drug Congress Europe 2014
    Date: 12-14 November, 2014
    Venue: Brussels, Belgium

    The World Orphan Drug Congress Europe offers partnering opportunities in the orphan and rare disease field. Key networking platforms include: Dedicated networking functions; Privately hosted meeting areas; Online partnering portal and access to free smartphone app; Personal networking managers to assist in meeting scheduling.
    For further information


    Media, Press & Publications

    Discover the new Journal of Neuromuscular Diseases

    The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.

    Product details:
    ISSN print: 2214-3599
    ISSN online: 2214-3602
    Volume: 1; 2 issues
    Status: First issue (1:1) published on 5 June 2014
    Next issue: 1:2 scheduled for December 2014
    Subject: Biochemistry, Medicine & Health,Neurosciences

    Carsten G. Bönnemann, National Institute of Neurological Disorders and Stroke/NIH, Bethesda, USA
    Hanns Lochmüller, Institute of Genetic Medicine Newcastle University, Newcastle upon Tyne, United Kingdom


    OrphaNews, The Newsletter of the Rare Diseases Community.
    OrphaNews is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
    and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Ségolène Aymé
    Editor: Antonia Mills
    Editors for Scientific Content: Catherine Pouzat, Sophie Höhn
    Contact Us
    Editorial Board: Ségolène Aymé, Paul Boom, Anna Bucsics, Kate Bushby, Barbara Cagniard, Lorenzo Dagna, Adam Heathfield, Lilian Lau, Yann Le Cam, Jordi Llinares-Garcia, Antoni Monserrat, Charlotte Rodwell, Gerhard Steffes, Till Voigtländer, Jaroslaw Waligora

    Orphanet Partner Country Representatives: Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Joerg Schmidtke (Germany), Helen Michelakakis (Greece), Eileen Treacy (Ireland), Annick Raas-Rothschild (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Vaidutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
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    Photo credit : Serimedis http://www.serimedis.inserm.fr/ (unless otherwise stated)