20 February 2014 print
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The much awaited ontology of rare diseases has just been released

All real knowledge which we possess depends on methods by which we distinguish the similar from the dissimilar. {Carolus Linnaeus (1707-1778)}

Jointly developed by Orphanet and the European Bioinformatics Institute (EBI), the Orphanet Rare Disease Ontology (ORDO) provides a structured vocabulary for rare diseases, capturing relationships between diseases, genes and other pertinent features, in a language directly understandable by computers. This is an all-inclusive and singular resource point for the ontological analysis of rare diseases.

Due to the substantial advances in genome technology in recent decades, we are now witnessing an increasing complexity of genetic data with greater dispersion of phenotypic data in clinical databases. Additionally the intricacy and multiplicity of scientific and medical terminologies has mandated the need for reference tools that integrate normalised data for use by systems health information and research.

The Orphanet database is world renowned for integrating rare disease nosology (classification of rare diseases), their relationships (gene- disease relations, epidemiological data , orphan drugs) and connections with other terminologies (MeSH, SNOMED CT, UMLS), genes or non-coding RNA loci related diseases connected to scientific databases (HGNC, OMIM, UniProt, Genatlas, Reactome, Ensembl, IUPHAR), or classifications (ICD10). This data is freely downloadable on a solid platform through Orphadata (www.orphadat.org).

The partnership with the European Bioinformatics Institute (EBI, Hinxton, UK) has facilitated the modelling of rare disease information mentioned above, generating an ontology with a robust and consistent structure that reveals significant relationships. In particular, it contains semantic relationships between genes and diseases: causal germ or somatic mutations, modifier genes, susceptibility genes, fusion genes involved in causation of tumours, genes with a major role in the phenotype of chromosomal abnormalities. This is an immense help for researchers as they can globally review rare disease relationships, classifications and allow cross referencing with other ontologies. Additionally, it is also characterised by inter-operability with other resources used by genetic databases. Thus, this alliance provides bioinformaticians and researchers a method to understand the associations between these wide-ranging data in a standardised format that is integrated with other IT environments

The official ontology of rare diseases produced and maintained by Orphanet (INSERM, US14). Orphanet classifications can be browsed in the Ontology Lookup Service (OLS) view. The Orphanet Rare Disease Ontology is updated monthly following the OBO guidelines on deprecation of terms. This ontology is available to all on BioPortal, EBI as well as Orphadata.

Spotlight on...
ECRIN-ERIC inauguration ceremony
The official inauguration of ECRIN-ERIC was hosted by the French Permanent Representation in Brussels on 30th January 2014. On 29th November 2013, ECRIN (European Clinical Research Infrastructure Network, www.ecrin.org) was officially awarded the status of European Research Infrastructure Consortium (ERIC), a legal status designed to facilitate the joint establishment and operation of research infrastructures of European interest. ECRIN-ERIC is a distributed infrastructure supporting multinational clinical research in Europe. ECRIN was developed and matured through the support of the European Union FP6 and FP7 programmes in a series of projects coordinated by Inserm. Germany, Spain, France, Italy and Portugal are the founding members of ECRIN-ERIC, whose management office is located in the host country (France), in Paris.

Robert-Jan Smits, Roger Genet and Jacques Demotes

The ceremony started with Robert-Jan Smits, Director General for Research and Innovation, DG RTD, European Commission, who handed over the ECRIN-ERIC plate, signifying the formal recognition of the ERIC status, and highlighted the support provided by the EU 7th Framework Programme during ECRIN development. Director-General Smits said: ‘It is a great pleasure for me to hand over the official name plate confirming the ERIC legal status of ECRIN. ECRIN-ERIC will bring more coherence and efficiency to the area of clinical research which is of crucial importance for Europe. By setting common standards and harmonising procedures and protocols between clinical trials centres, the ECRIN-ERIC will further strengthen the European Research Area.”

Government representatives of the ECRIN-ERIC member countries (Roger Genet, Director General for Research Innovation, French Ministry of Higher Education and Research, Renate Loskill, Head of Division ‘Health Research’, German Federal Ministry of Education, Fabrizio Oleari, President of Istituto Superiore di Sanità, Italy, Antonio Andreu, Director General, Instituto de Salud Carlos III, Spain, and Paulo Pereira, Vice-President Fundação para a Ciência e Tecnologia, Portugal) highlighted, in the context of the national policy on health research and on research infrastructures, the importance of cooperation to foster competitiveness in clinical research and in health innovation. Silvio Garattini, Chair of ECRIN Scientific Board and Director of the Mario Negri Institute, Milan, addressed the need for multinational cooperation in independent clinical trials, then Jacques Demotes, ECRIN-ERIC Director General, presented an overview of ECRIN-ERIC development and activities. Finally Ruxandra Draghia-Akli, Director, Health, demographic change and wellbeing challenge, DG RTD, European Commission, discussed clinical trials in the context of the H2020 programme, and his Excellency Philippe Etienne, French Ambassador at the European Union, closed the discussion with considerations on the integration of Europe’s scientific policies and capacities.

ECRIN-ERIC, an infrastructure for multinational clinical research in Europe
Clinical trials represent a critical step in health innovation, as the only way to demonstrate efficacy and safety in patients. Clinical trials are also essential instruments for health systems, as comparing established treatments is the basis for optimisation of healthcare strategies and for evidence-based medical practice. Access to patients and to medical expertise are key factors in the conduct of clinical trials. ECRIN-ERIC was therefore designed to facilitate multinational trials in spite of the fragmentation and poor interoperability of national clinical trial legislation, of health systems, of competent authorities and ethics committees, of national research infrastructures, of tools and procedures, of training, of funding and of language. ECRIN-ERIC boosts the competitiveness of Europe, taking advantage of its potential patient population size and its medical expertise.

Antonio Andreu, Ruxandra Draghia-Akli, Jacques Demotes, Fabrizio Oleari, Roger Genet, Renate Loskill, Paulo Pereira, Philippe Etienne, Silvio Garattini and Christian Ohmann

In individual countries, academic sponsors, clinical research centres or clinical trial units have the capacity to conduct national trials, but face major obstacles in the management of multinational trials. By connecting and coordinating these national centres and networks, ECRIN-ERIC makes it possible to conduct multinational trials in Europe. For this purpose, ECRIN-ERIC establishes permanent contracts with its national scientific partners. ECRIN-ERIC therefore provides, at not-for-profit cost, operational support in the conduct of multinational trials whose protocol is accepted by the ECRIN-ERIC Scientific Board, based on their scientific excellence. This support includes information and consulting before protocol finalisation then, after protocol review, operational services supporting the management of the trial in multiple countries (ethical and regulatory submissions, pharmacovigilance, monitoring, data management). ECRIN-ERIC European Correspondents, hosted in each national hub, ensure coordinated support to clinical trial operations.

Members of ECRIN-ERIC also benefit from a series of structuring activities enhancing the competitiveness of the national partners and of the European network as a whole, developing harmonised practice, tools for multinational collaboration, training, and high quality standards. For instance ECRIN-ERIC develops a certification policy to promote quality and interoperability in clinical trial management. ECRIN-ERIC also promotes harmonisation of the regulatory systems, in Europe and other world regions, shared ethical standards, transparency and optimal use of data, with the objective to stay at the forefront of methodological and technological development in clinical research.

ECRIN-ERIC thus represents a major instrument for health innovation and for the optimisation of healthcare strategies, fostering the competitiveness of European health industry, and promoting evidence-based medical practice for the benefit of healthcare systems, of healthcare professionals, and of European patients and citizens.
Press release provided by ECRIN for dissemination

Currently the ECRIN Hub for rare diseases is coordinated by the INSERM US14, which also hosts Orphanet and the scientific secretariat of the IRDiRC.
Visit the ECRIN website


Save the date: 7-9 November, 2014 for the second IRDiRC conference in Shenzhen, China
The International Rare Diseases Research Consortium (IRDiRC) will organize its next conference in Shenzhen, China, with the collaboration of the Beijing Genomics Institute (BGI). The conference aims to gather stakeholders active in the rare disease area from across the globe. It will be held on 7-9 November 2014, with two days of conference and one day of satellite events (for Chinese participants). There will be four parallel tracks: Diagnostics / Therapies / Infrastructures - Technologies / Educational track. Registration for this exciting event will be open shortly.


National & International Policy Developments
Other International News
11th national NCL Congress on Molecular mechanisms of axonal and neuronal degeneration
The disease Neuronal Ceroid Lipofuscinosis (NCL), also named Batten disease, is an orphan disease, thus having a very low awareness level. The juvenile form of NCL, caused by a deletion located within the CLN3 gene, reveals the first symptoms at an age of six to eight. The children suffer a rapid loss of eye-sight, followed by epileptic seizures and a degradation of the mental and motor skills. Since there is no therapy for NCL yet, the course of disease ends with the death of the patients usually at an age of around 30 years. To close this gap in treatment, the NCL Foundation supports research in the field of NCL and networking of scientists of different areas. A perfect opportunity for this scientific exchange is given by the NCL Congress which is organized by the NCL Foundation every year. In December 2013, international scientists met in Hamburg to present and discuss their current research results concerning the molecular mechanisms of axonal and neuronal degeneration. Besides the established CLN3-mouse model, the zebrafish was presented as a new model system useful for up-scaled drug testing. To provide a better copy of the human symptoms caused by NCL, Prof. David Pearce and his team are developing a pig model for NCL. This is a promising new approach for a model system that might ease the search for a reasonable drug target. The scientific exchange was widened by the expertise of scientists who work on other diseases and novel imaging techniques, and also joined the meeting. Thus, one of the topics intensively discussed was the question how relevant findings concerning other diseases can be helpful for the research of the lysosomal storage disease NCL. For instance, Dr. Jakub Sikora from the Albert Einstein College of Medicine in New York provided a deeper insight into one major neuropathological component of different lysosomal storage diseases, the neuroaxonal dystrophy. The keynote speaker of the 11th NCL Congress, Prof. Klaus-Armin Nave emphasized the interplay of oligodendrocytes and axons, which might be an important factor in neurodegenerative diseases. The NCL Congress was also an excellent platform for the successful initiation and extension of research collaborations. This encourages the NCL Foundation to believe in the goal of developing the first therapy approach by 2020.
More information about the NCL Foundation can be found here: www.ncl-foundation.com

Guidance Documents and Recommendations
Guidelines on pharmacogenomics drafted by the EMA
More and more medicinal products authorised by the European Medicines Agency (EMA) contain pharmacogenomic information in their Summary of Product Characteristics. Pharmacogenomics is the study of variations of DNA and RNA characteristics as related to drug response. Nowadays, pharmacogenomics is part of the development and the marketing (post-authorisation) phase for several medicines.
The EMA published its first pharmacogenomic guideline in 2012, in order to promote the integration of pharmacogenomics in product development for patient treatment. This guideline provides in-vitro and in-vivo cut-off values to guide industry drug development.
As serious adverse drug reactions have already been identified after marketing authorization, the EMA has draft a second guideline on key aspects for the use of pharmacogenomic methodologies in the pharmacovigilance evaluation of medicinal products.
With the drafting of these two guidelines, the EMA intends to further enable the potential of pharmacogenomic during drug development and surveillance, and gain insight into the associated scientific challenges such as translating data from pharmacogenomic studies into clinically relevant product information, as well as discuss potential solutions.
It is too early to measure the impact of these guidelines, however, they are expected to improve genomic data-informed drug development and clinical experience so that patients and public can benefit from the advancements of genomic science and technology.
Access the abstract
Access the EMA guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products
Access the EMA guideline on key aspects for the use of pharmacogenomic methodologies in the pharmacovigilance evaluation of medicinal products

A scientific statement from the American Heart Association on prevention and treatment of thrombosis in pediatric and congenital heart disease
Consult the Pubmed abstract
Circulation ; 128(24):2622-703 ; December 2013
Physical activity in adolescents and adults with congenital heart defects: individualized exercise prescription
Consult the Pubmed abstract
Eur Heart J. ; 34(47):3669-74 ; December 2013
Enteropancreatic endocrine tumor: recommendations for management of patients with liver metastases
Consult the Pubmed abstract
To read more about "Enteropancreatic endocrine tumor"

Lancet Oncol. ; 15(1):e8-e21 ; January 2014
Bioinformatics, Registries and Data Management
EUROCAT helps the better understanding oculo-auriculo-vertebral spectrum
Oculo-auriculo-vertebral spectrum (OAVS) is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. The authors of an article published in European Journal of Human Genetics used the congenital anomalies registries in Europe EUROCAT, a large network of population-based congenital anomaly registries in Europe, to provide population-based information on OAVS patients, including the total prevalence and birth outcomes during the 1990–2009 period. They analysed the data of 355 infants diagnosed with oculo-auriculo-vertebral spectrum from 34 registries active in 16 European countries. The authors found using the EUROCAT registry was extremely helpful to understand the the high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.
Consult the Pubmed abstract

YODA has a possible answer to open access for sharing clinical trial data
The recently developed Yale University Open Data Access Project (YODA) Project model provides a methodology to patients and physicians for the rigorous and objective evaluation of clinical trial data. According to YODA, the project "ensure(s) that all necessary information about a drug or device when making treatment decisions" is provided without compromising data privacy. YODA helps in coordinating with the industry by analysing every request for clinical data scientifically in a manner that is precise, unbiased and fair. They do this by systematically examining all the relevant product data by "two separate qualified research groups and making all patient-level clinical research data available for analysis by other external investigators". The model is notable as it is designed to promote transparency as well as to protect against industry influence. They require companies that avail the service of YODA to provide all relevant product data. After a systematic analysis of the product data an independent Steering Committee, which includes leaders in the field of clinical research and biomedical ethics, advise the YODA project team A Clinical Advisory Committee. The YODA project emaphasises that "(their) leadership is committed to transparency, publication, and making the data publicly available".

Johnson & Johnson announced a partnership with YODA, in which they will share raw data from many of its clinical trials. This initiative in part belongs to a broader shift in both the United States and Europe, where researchers and some regulators are increasingly frustrated by the secrecy surrounding many drug trials, and want to get the information out in the open.
Go to the YODA website

Screening and Testing
Carrier screening for cystic fibrosis: how efficient would it be?
Newborn screening for Cystic Fibrosis (CF) has now been implemented in the majority of countries where CF is common, including North America, Australia and several parts of Europe. Carrier screening is less extensively used, but has been growing in acceptance, and it is offered to females or couples in the USA and in parts of Europe and Australia. In the USA carrier screening has been recommended by the American College of Obstetricians and Gynaecologists and by the American College of Medical Genetics, and, although there is not an established public health programme, millions of carrier tests have been performed. The authors of an article published in European Respiratory Journal describes some of the advantages and disadvantages of carrier screening. The authors believe that the advantages of the introduction of CF newborn screening is that it has been added to existing newborn screening programmes, which significantly defrays the cost. However, they believe that CF newborn and carrier screening have complementary roles and neither can replace the other. In contrast to newborn screening, carrier screening allows informed reproductive choices before the birth of a child with CF. A disadvantage of carrier screening that the authors believe is significant is that it may get infants into care earlier than newborn screening, but would miss more affected babies.
Consult the Pubmed abstract

Newborn Screening for Fragile X Syndrome
Fragile X syndrome (FXS), caused by a tri-nucleotide expansion (>200 CGG repeats) in the fragile X mental retardation gene (FMR1), is currently not included in newborn screening (NBS) panels in the United States as it does not meet the standards for recommendation. The recent advances in genomic testing as well as groundbreaking advances in targeted treatment for FXS have been challenging the dogma and principle of the national NBS program: screen only if you can intervene. An article published in Clinical Review & Education provides arguments in favour of NBS which include benefits of early intervention and follow-up for the identified baby, which would justify NBS even in the absence of medical benefit to the child. In addition, the extended family members may benefit from genetic and reproductive counselling, informed decision making before a subsequent pregnancy, and access to treatment and services.

The authors also point to a controversial issue of the identification of premutation carriers (55-200 CGG repeats), because it not only can lead to information on the reproductive possibility of having a child with FXS but also leads to information about personal health risks associated with the premutation. If NBS for FXS is developed, it must be carried out with clear awareness of the potential impact on the lives of the children, and it should be done after counselling and parents’ informed consent. Importantly, the infrastructure to support testing, counselling, treatment, and follow-up will have to be made available to the families.
Consult the Pubmed abstract


Ethical, Legal & Social Issues
Quality of Life in Children and Adolescents with Spinal Muscular Atrophy and their parents in the Czech Republic is lower than U.S.
An article published in Pediatric Neurology has reported on the quality of life of children suffering from spinal muscular atrophy in the Czech Republic comparing it to the data obtained from U.S. Spinal muscular atrophy is a rare hereditary neuromuscular disorder that has high impact on debilitating patients and, in most cases, on shortening their life expectancy. Although there is no causal therapy, improvements in symptomatic therapy have extended the patients’ life expectancy and increased their quality of life. Unfortunately, the advancements in care vary in different countries. The authors found that compared to the U.S. data, the Czech data generally show a lower quality of life, mainly in the family resources part. The highest score was achieved in the part about communication. Altogether, the parents’ scores are lower than those of the children. In the Czech Republic SMA patients and, especially their parents, have a significantly lower quality of life when compared to the U.S. patients, mostly due to economy factors and social facilities. The authors believe that these results imply that there is a need for family support through social care as well as civic or patients’ organizations’ support.
Consult the abstract


New Syndromes

Novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal caused by mutations in the T gene
The authors described for the first time four patients from three consanguineous families with a syndrome with sacral agenesis, a persistent notochordal canal and abnormal ossification of the vertebral bodies. Sequencing of the T gene (brachyury gene) in the affected individuals led to the identification of a homozygous missense mutation linked to this syndrome.
Consult the Pubmed abstract

J Med Genet. ; 51(2):90-7 ; February 2014
Syndromic severe intellectual deficiency in male patients due to truncating mutations in IQSEC2
The authors reported on three male patients with intellectual deficiency, midline stereotypic hand movements, hypotonia, hyperkinesia, strabismus, as well as seizures, and non-inherited and postnatal onset microcephaly. They proposed that truncating mutations in IQSEC2 are responsible for syndromic sever intellectual deficiency in male patients.
Consult the Pubmed abstract

Eur J Hum Genet. ; 22(2):289-92 ; February 2014

New Genes

Inherited cerebral palsy associated with a homozygous mutation in ADD3 in a multiplex consanguineous Jordanian family
Consult the Pubmed abstract
To read more about "Inherited congenital spastic tetraplegia"

Ann Neurol. ; 74(6):805-14 ; December 2013
Migrating partial seizures in infancy: SLC25A22 variant identified in a consanguineous pedigree
Consult the abstract
To read more about "Malignant migrating partial seizures of infancy"

Annals of Neurology ; 74(6):873-882 ; December 2013
Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1 in ten patients from eight families
Consult the Pubmed abstract
Ann Neurol. ; 74(6):914-9 ; December 2013
Congenital disorders of glycosylation: exome sequencing identified MAN1B1 mutations in seven patients with slight facial dysmorphism, psychomotor delay and truncal obesity
Consult the Pubmed abstract
To read more about "Congenital disorder of glycosylation"

PLoS Genet. ; 9(12):e1003989 ; December 2013
Isolated complex III deficiency: homozygous UQCC2 mutation at cause in a patient with severe intrauterine growth retardation, neonatal lactic acidosis and renal tubular dysfunction
Consult the Pubmed abstract
To read more about "Isolated CoQ-cytochrome C reductase deficiency"

PLoS Genet. ; 9(12):e1004034 ; December 2013
Boucher-Neuhäuser syndrome, Gordon Holmes syndrome, and cases of early onset spastic ataxia/hereditary spastic paraplegia are caused by PNPLA6 recessive mutations
Consult the Pubmed abstract
To read more about "Ataxia - hypogonadism - choroidal dystrophy"
To read more about "Cerebellar ataxia - hypogonadism"

Brain ; 137(Pt 1):69-77 ; January 2014
Renal Fanconi’s syndrome: identification of a heterozygous missense mutation in EHHADH in members of a five-generation black family
Consult the Pubmed abstract
To read more about "Primary Fanconi syndrome"

N Engl J Med. ; 370(2):129-38 ; January 2014
Gray platelet syndrome associated with a dominant nonsense mutation in GFI1B
Consult the Pubmed abstract
To read more about "Gray platelet syndrome"

N Engl J Med. ; 370(3):245-53 ; January 2014
Fryns-Aftimos syndrome (pachygyria, epilepsy, intellectual deficit and dysmorphism): early and severe manifestation of Baraitser-Winter syndrome due to ACTB mutations
Consult the Pubmed abstract
To read more about "Pachygyria - epilepsy - intellectual deficit - dysmorphism"

Eur J Hum Genet. ; 22(2):179-83 ; February 2014
X-linked nonsyndromic sensorineural hearing loss with cochlear malformation caused by a mutation in COL4A6
Consult the Pubmed abstract
To read more about "X-linked nonsyndromic sensorineural deafness type DFN"

Eur J Hum Genet. ; 22(2):208-15 ; February 2014
Familial atrial fibrillation associated to a novel PITX2 loss-of-function mutation
Consult the Pubmed abstract
To read more about "Familial atrial fibrillation"

Eur J Med Genet. ; 57(1):25-31 ; January 2014
Infantile bilateral striatal necrosis due to mutations in ADAR1
Consult the Pubmed abstract
To read more about "Infantile bilateral striatal necrosis"
To read more about "Familial infantile bilateral striatal necrosis"

J Med Genet. ; 51(2):76-82 ; February 2014
Autosomal recessive spastic ataxia, paraparesis and cerebellar dysfunction: nonsense and missense mutations in KIF1C identified in two consanguineous families
Consult the Pubmed abstract
To read more about "Autosomal recessive spastic ataxia"

J Med Genet. ; 51(2):137-42 ; February 2014
Autosomal recessive cerebrofaciothoracic dysplasia caused by TMCO1 deficiency in Turkish families
Consult the Pubmed abstract
To read more about "Cerebro-facio-thoracic dysplasia"

Am J Med Genet A. ; 164(2):291-304 ; February 2014
Growth deficiency - brachydactyly – dysmorphism (Frias syndrome) may be due to haploinsufficiency of BMP4
Consult the Pubmed abstract
To read more about "Growth deficiency - brachydactyly - dysmorphism"

Am J Med Genet A. ; 164(2):338-45 ; February 2014
Autosomal recessive early-onset inflammatory bowel disease: TTC7A mutations identified in five infants with variable phenotype including lymphopenia and intestinal atresia
Consult the Pubmed abstract
To read more about "Autosomal recessive early-onset inflammatory bowel disease"

Gastroenterology ; [Epub ahead of print] ; January 2014
Congenital hypothyroidism due to thyroid development defects, including thyroid hypoplasia and athyreosis, associated with SLC26A4 mutations
Consult the Pubmed abstract
To read more about "Thyroid hypoplasia"
To read more about "Athyreosis"

J Clin Endocrinol Metab. ; 99(1):E169-76 ; January 2014
Dense granule disease: alterations in FLI1 and RUNX1 may be common in patients with platelet dense granule secretion defects and mild thrombocytopenia
Consult the Pubmed abstract
To read more about "Dense granule disease"

Blood ; 122(25):4090-3 ; December 2013
Familial patients with multiple café au lait spots and Noonan syndrome-like facial features linked to a mutation in MAP2K2
Consult the Pubmed abstract
To read more about "Neurofibromatosis - Noonan syndrome"

Am J Med Genet A. ; 164(2):392-6 ; February 2014
Kawasaki disease: first evidence supporting the association between TARC/CCL17 polymorphisms, susceptibility of the disease, and intravenous immunoglobulin treatment responses
Consult the Pubmed abstract
To read more about "Kawasaki disease"

Pediatr Res. ; 74(5):545-51 ; November 2013

Research in Action

Clinical Research
Familial amyloid polyneuropathy: the use of diflunisal for two years reduced the rate of progression of neurological impairment and preserved quality of life
Consult the Pubmed abstract
To read more about "Familial amyloid polyneuropathy"

JAMA ; 310(24):2658-67 ; December 2013
Oculopharyngeal muscular dystrophy: autologous myoblast transplantation in the pharyngeal muscles seems to be a safe and efficient procedure
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Oculopharyngeal muscular dystrophy"

Mol Ther. ; 22(1):219-25 ; January 2014
Nasopharyngeal carcinoma: chemotherapy in combination with adoptive T-cell transfer achieves one of the best survival outcomes in patients with advance disease
Consult the Pubmed abstract
To read more about "Nasopharyngeal carcinoma"

Mol Ther. ; 22(1):132-9 ; January 2014
Hepatoblastoma: high-intensity focused ultrasound combined with transarterial chemoembolization is as safe and promising method
Consult the Pubmed abstract
To read more about "Hepatoblastoma"

Hepatology ; [Epub ahead of print] ; June 2013
Esophageal adenocarcinoma: docetaxel can be recommended as an appropriate second-line treatment for patients with disease refractory to treatment with platinum and fluoropyrimidine
Consult the Pubmed abstract
To read more about "Esophageal adenocarcinoma"

Lancet Oncol. ; 15(1):78-86 ; January 2014
Follicular lymphoma: the combination of pidilizumab plus rituximab is well tolerated and active in patients with relapsed disease
Consult the Pubmed abstract
To read more about "Follicular lymphoma"

Lancet Oncol. ; 15(1):69-77 ; January 2014
B-cell chronic lymphocytic leukemia: encouraging safety and activity of ibrutinib in elderly, previously untreated patients
Consult the Pubmed abstract
To read more about "B-cell chronic lymphocytic leukemia"

Lancet Oncol. ; 15(1):48-58 ; January 2014
Ataxia-telangiectasia: EryDex treatment led to a significant improvement in neurological symptoms, without association with the typical steroid side effects
Consult the Pubmed abstract
To read more about "Ataxia-telangiectasia"

Orphanet J Rare Dis. ; 9(1):5 ; January 2014
Creutzfeldt-Jakob disease: doxycycline was well tolerated but did not significantly affect the course of the disease
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Creutzfeldt-Jakob disease"
To read more about "Inherited Creutzfeldt-Jakob disease"

Lancet Neurol. ; 13(2):150-8 ; February 2014
Donor-derived allogeneic anti-CD19-CAR T cells can cause regression of B-cell malignancies resistant to standard donor lymphocyte infusions
Consult the Pubmed abstract
To read more about "B-cell chronic lymphocytic leukemia"
To read more about "Mantle cell lymphoma"

Blood ; 122(25):4129-39 ; December 2013
Fanconi anemia: best survival benefit in patients transplanted before 10 years with bone marrow after a fludarabine-based regimen
Consult the Pubmed abstract
To read more about "Fanconi anemia"

Blood ; 122(26):4279-86 ; December 2013
Severe hemophilia A: a novel recombinant factor VIII with prolonged half-life, rFVIIIFc, was well tolerated and resulted in low bleeding rates
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Severe hemophilia A"

Blood ; 123(3):317-25 ; January 2014
Idiopathic pulmonary arterial hypertension: the use of anticoagulation is associated with a survival benefit in patients
Consult the Pubmed abstract
To read more about "Idiopathic and/or familial pulmonary arterial hypertension"
To read more about "Idiopathic pulmonary arterial hypertension"

Circulation ; 129(1):57-65 ; January 2014
Prader-Willi syndrome: N-acetylcysteine treatment could help in limiting skin-picking, a component of behavioral troubles that can result in serious skin infections
Consult the Pubmed abstract
To read more about "Prader-Willi syndrome"

Am J Med Genet A. ; 164(2):421-4 ; February 2014
Stem Cells

Glioblastomas: intrasanal delivery of mesenchymal stem cells significantly extends survival of irradiated mice with experimental brain tumours
Consult the Pubmed abstract
To read more about "Glial tumor"
To read more about "Glioblastoma"

Mol Ther. ; 22(1):140-8 ; January 2014
Huntington disease: transplant of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in transgenic rat model
Consult the Pubmed abstract
To read more about "Huntington disease"

Stem Cells ; 32(2):500-9 ; February 2014
Gene Therapy
X-linked centronuclear myopathy: adeno-associated virus-mediated gene therapy prolongs survival and restores muscle function in murine and canine models
Consult the Pubmed abstract
To read more about "X-linked centronuclear myopathy"

Sci Transl Med. ; 6(220):220ra10 ; January 2014
Amyotrophic lateral sclerosis: widespread spinal cord transduction by intrathecal injection of rAAVrh10 expressing miRNA targeting SOD1 slowed the disease progression in model mice
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis"

Hum Mol Genet. ; 23(3):668-81 ; February 2014
Reversibility of neuropathology in Tay-Sachs-related diseases appears limited as it was not achieved after early manifestation of the disease in a mouse model of Sandhoff disease
Consult the Pubmed abstract
To read more about "Sandhoff disease"

Hum Mol Genet. ; 23(3):730-48 ; February 2014
Hemophilia A and B: platelet gene therapy corrects the hemophilic phenotype in model mice
Consult the Pubmed abstracts
To read more about "Hemophilia B"
To read more about "Hemophilia A"

Mol Ther. ; 22(1):169-77 ; January 2014
Blood ; 123(3):395-403 ; January 2014
Therapeutic Approaches

Pantothenate kinase-associated neurodegeneration: panthetine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a mouse model
Consult the Pubmed abstract
To read more about "Pantothenate kinase-associated neurodegeneration"

Brain ; 137(Pt 1):57-68 ; January 2014
Isolated aniridia: early postnatal manipulation of Pax6 dosage reverses congenital tissue malformation defects in mice
Consult the Pubmed abstract
To read more about "Isolated aniridia"

J Clin Invest. ; 124(1):111-6 ; January 2014
Alpha-1-antitrypsin deficiency: antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin-related liver disease in mice
Consult the Pubmed abstract
To read more about "Alpha-1-antitrypsin deficiency"

J Clin Invest. ; 124(1):251-61 ; January 2014
West syndrome: neonatal estradiol stimulation prevents epilepsy in Arx mouse model of X-linked infantile spasms syndrome
Consult the Pubmed abstract
To read more about "West syndrome"

Sci Transl Med. ; 6(220):220ra12 ; January 2014
Familial or sporadic hemiplegic migraine: the pro-oxidant BHQ, a Cav2.1 gating modifier, can ameliorate defects associated with a disease-causing mutation in Cav2.1
Consult the Pubmed abstract
To read more about "Familial or sporadic hemiplegic migraine"

Neuron ; 81(1):91-102 ; January 2014
Proximal spinal muscular atrophy: VPAC2 receptor agonist BAY 55-9837 increases SMN protein levels and moderates disease phenotype in mouse models
Consult the Pubmed abstract
To read more about "Proximal spinal muscular atrophy"

Orphanet J Rare Dis. ; 9(1):4 ; January 2014
Systemic sclerosis: CDDO, a synthetic PPAR-γ agonist, significantly ameliorated dermal fibrosis in two mouse models
Consult the Pubmed abstract
To read more about "Systemic sclerosis"
To read more about "Localized scleroderma"

Ann Rheum Dis. ; 73(2):446-54 ; February 2014
Acute myeloid leukemia: cell-targeted STAT3 silencing and TLR9 triggering generate systemic antitumor immunity in a mouse model
Consult the Pubmed abstract
To read more about "Acute myeloid leukemia"

Blood ; 123(1):15-25 ; January 2014
Immune thrombocytopenic purpura: allogeneic platelet transfusions prevent murine T-cell mediated immune thrombocytopenia
Consult the Pubmed abstract
To read more about "Immune thrombocytopenic purpura"

Blood ; 123(3):422-7 ; January 2014
Blocking von Willebrand factor seems promising for treatment of cutaneous inflammation in patients suffering from immune complex-mediated vasculitis
Consult the Pubmed abstract
To read more about "Immune complex mediated vasculitis"
To read more about "Cutaneous leukocytoclastic angiitis"

J Invest Dermatol. ; 134(1):77-86 ; January 2014
Hepatocellular carcinoma: a novel RNA oligonucleotide improves liver function and inhibits carcinogenesis in a rat model
Consult the Pubmed abstract
To read more about "Hepatocellular carcinoma"

Hepatology ; 59(1):216-27 ; January 2014
Diagnostic Approaches

Limbic encephalitis with NMDA receptor antibodies: the sensitivity of NMDA receptor antibody testing is higher in cerebrospinal fluid (CSF) than in serum
Consult the Pubmed abstract
To read more about "Limbic encephalitis with NMDA receptor antibodies"

Lancet Neurol. ; 13(2):167-77 ; February 2014

Patient Management and Therapy
Rasmussen subacute encephalitis: review on clinical features, pathobiology and treatment advances
Consult the Pubmed abstract
To read more about "Rasmussen subacute encephalitis"

Lancet Neurol. ; 13(2):195-205 ; February 2014
Heavy chain deposition disease: an overview
Consult the Pubmed abstract
To read more about "Heavy chain deposition disease"

Clin Exp Nephrol. ; 17(6):771-8 ; December 2013
Single amino acid supplementation in aminoacidopathies: a systemic review
Consult the Pubmed abstract
To read more about "Disorder of amino acid and other organic acid metabolism"

Orphanet J Rare Dis. ; 9(1):7 ; January 2014
McCune-Albright syndrome: routine screening by magnetic resonance imaging including both pancreatobiliary and liver sequences should be performed in patients
Consult the Pubmed abstract
To read more about "McCune-Albright syndrome"

J Clin Endocrinol Metab. ; 99(1):E97-E101 ; January 2014
One new Clinical Utility Gene Card published in the European Journal of Human Genetics
EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases.
The European Journal of Human Genetics has published one new Clinical Utility Gene Card for:
Phosphomannomutase 2 deficiency


Orphan Drugs
Renewed hope for the Duchenne muscular dystrophy exon skipping treatment, drisapersen
Although Prosensa's Duchenne muscular dystrophy exon skipping treatment, drisapersen, suffered a setback at its Phase III trial (Read about results on OrphaNews ), a deeper examination of the data has revealed that all may not be lost for the drug. Prosensa has revealed that after analysing the drisapersen's results further, it was observed that administering the drug earlier in the disease and treating longer can delay the progression of DMD.

According to their data, in the 96-week extension data from a Phase III study, patients on continual treatment could walk 49 meters farther in a 6-minute walking test than those who took placebo for 48 weeks before switching to drisapersen, the company has released a statement, emphasising that "These data encourage us to engage patient groups, clinical experts and regulators to explore a path forward for drisapersen, which includes the possibility of re-dosing". Prosensa’s partner, GlaxoSmithKline has exited from the collaboration, but the new analysis of drisapersen's data has renewed the prospects of the Dutch company as its share prices have soared by 25%.

Pluripotent stem cells in regenerative medicine: the road ahead
The potential of stem cells as an unlimited cells source of cells as well as its promise in being able to differentiate cells into disease-relevant cell types has led to several research efforts gathering significant preclinical success. Thus bringing human pluripotent stem cells (hPSCs) from bench to bedside is not a distant dream. However, the preparedness of academia as well as the industry for this eventuality is not certain.

In an article published in Nature Genetics Reviews the authors have described how the stage is set for clinical translation of stem cell treatments. The authors have described the greatly improved protocols that are now available for directed differentiation which has led to the production of vastly superior technology leading to the derivation of therapeutically relevant cell types from hPSC sources. The authors have exemplified recent breakthroughs in the therapeutic development for many cell lineages that have neural as well as non-neural identities. Although there are roadblocks and challenges, the authors have described the tools that helped this differentiation process, where small molecules and recombinant proteins play an important role but have also described matrigels and other three dimensional matrices. They also emphasised the progress made in directed differentiation through transcriptional programming. They have also described how recent in-vitro and imaging technology will be able to address whether the hPSCs have reached the specific fates meant for them and whether they are performing the function that they are meant to perform.

The authors then provide one of the challenging aspects of bringing (hPSC)-derived cells from laboratory into market authorisation. They have provided the readers with a roadmap that will help towards clinical translation. The authors’ advice that following a preclinical proof of concept, it is important to validate robustness in relevant disease models and to develop a cell-manufacturing strategy that is suitable for clinical translation. Important steps include producing cells at a sufficient scale (that is, creating a cell bank) and using fully standardized protocols under current good manufacturing practice (GMP)-compliant conditions. The resulting bank of the candidate therapeutic cell product needs to be revalidated for safety and efficacy before it can be considered as a candidate clinical product for early safety studies, and eventually efficacy studies, in human patients.
Consult the Pubmed abstract

Regulatory News
Recent positive opinions adopted by the committee of medicinal products for human diseases
On 23 January 2014, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Bemfola intended for the treatment of fertility disorders. The applicant for this medicinal product is FINOX Biotech AG.
Read the positive opinion

On 23 January 2014, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Adempas, 0.5 mg, 1 mg, 1.5 mg, 2.0 mg and 2.5 mg, film-coated tablets intended for the treatment of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension. The applicant for this medicinal product is Bayer Pharma AG.
Read the positive opinion

Political and Scientific News
NIH inventions translate into drugs and biologics with high public impact
The role of National Institute of Health (NIH) in leading translational success of drugs is not widely known. After 1980, two legislations passed in the United States, the Bayh-Dole Act, the Stevenson-Wydler technology Innovation Act, allowed and incentivised technology transfer from government funded institutions to the private sector for commercialization. Whether these legislative changes have helped in procuring more drugs into the market is a point of contention. It has been shown that public-sector research institutions (PSRIs) have had a more immediate effect on improving public health than was previously realised as they have contributed significantly towards drug development (http://www.nejm.org.gate2.inist.fr/doi/pdf/10.1056/NEJMsa1008268). Now a study shows that the NIH-Intramural Research Program (IRP) has had a disproportionately high level of impact on bringing drugs to the market through the US Food and Drug Administration (FDA).

An in-depth comparison of the specific contributions of the NIH-IRP and other PSRIs to the development of drugs and biologics approved by the FDA published in Nature Biotechnology. The authors, who belong to the Office of Technology Transfer at NIH, have procured data which reveals that NIH-IRP inventions have had a disproportionately greater impact as the largest institutional contributor to the PSRI drugs. Among other categories, NIH-IRP has had a great impact on the number of drugs that has been granted orphan status and the number of drugs developed under New Drug Applications (NDAs) granted priority review by the FDA because they offer major advances in treatment, through to 2007.

Out of all the FDA-approved drugs, 153 drugs materialised from inventions in extramural PSRIs or NIH-IRP, out of which 14.4% of the drugs have received licences from NIH-IRP alone. The authors have thus revealed that the NIH-IRP contributions to obtaining market authorisations are disproportionately large relative to its level of funding (11.2% of all NIH research funds). While NIH-IRP has made higher contributions towards some therapeutic categories than others, they have significantly overshadowed extramural PSRI’s in contributing towards FDA approved drugs. Notably, 15% of the 39 PSRI drugs that received orphan status by the FDA used licensed technology from the NIH-IRP. Another compelling statistic provided by the authors is that that while the funding for NIH-IRP in 2010 was around $3.3 billion, the global net sales accounted by drugs and biologics that were due to inventions coming from NIH-IRP have amounted to at least $6.9 billion.

The percentage of large companies executing the licences for inventions from NIH-IRP exceeds small companies or start-ups, which is different from other PSRIs where smaller companies and start-ups have played a larger role. This is possibly because NIH-IRP cannot actively participate in the formation of a company around the institution’s inventions while other PSRIs can and thus be more involved with startup or spinoff companies.

The success of the NIH-IRP technology transfer program may be related to its resources and structures where scientists have access to high-quality resources and the opportunity to address biomedical challenges in a relatively stable funding environment. Furthermore, the authors also highlight the high-quality technology transfer infrastructure at NIH, which makes the transmission of licences smooth and quick.
Consult the Pubmed abstract

Could the advances in human genetics be an opportunity for drug development?
A fascinating article published in Nature Biotechnology provides an interesting perspective on human genetics to be perhaps the single best opportunity to innovate and improve clinical success rates in drug development. Genetic screens are comparatively unbiased, and provide a causative link between a sequence variant and a phenotype. There is little doubt that genetics plays a major role in the risk (and pathogenesis) of most if not all common human diseases. The authors believe that once a pathogenic biochemical pathway has been pinpointed, drug hunters can embark on the difficult journey to correct or neutralize it. Taking the most direct route, they can exploit the protein encoded by the gene variant as a drug target; alternatively, they can act against other proteins in the same biochemical pathway; or finally they can attempt to counter the destructive effects of the biochemical pathway by up- or down-regulating another pathway that affects the same physiologic function.

The authors have performed a post hoc assessment of phase 3 successes and failures (during the period: 2000–2008) which supports their case for genetics as a positive predictor. All targets with clear genetic evidence and good pharmacologic agents in this set produce the clinical effect predicted by human genetics. The authors also provide other advantages of human genetics as it gives functional insights that liberate the target selection process from poorly predictive animal models. Genetic experiments can be designed without a priori assumptions about the nature of the disease as they are largely independent of models and hypotheses. This is particularly important for an industry that is on a slippery slope in terms of declining business success.

Genetically defined targets offer the opportunity to determine if candidate drugs directed against these targets can correct the biochemical defects, before the launch of lengthy and expensive clinical endpoint trials. They may allow shorter, less expensive registration studies based on surrogate endpoints, rather than disease outcomes such as survival—so long as surrogate and outcome endpoints can be linked by convincing human genetics studies.

The authors have also provided an example where large and very costly clinical trials were performed in an attempt to show that agents that increase levels of HDL protect against coronary artery disease. The results to date suggest that raising HDL does not, by itself, affect the risk of getting cardiovascular diseases but the discovery of a rare variant of proprotein convertase subtilisin/kexin type 9 (PCSK9), which lowers LDL cholesterol substantially and decreases the risk of early-onset heart attack, was an important advance. The authors highlight the several pharmaceutical companies have developed antibody inhibitors of PCSK9 and have shown that they dramatically lower levels of LDL cholesterol in people and are well tolerated.
Consult the Pubmed abstract



SMA Europe announces its 6th international Call for SMA Research Projects
This new Call for SMA Projects will be open to any research project aimed at finding a therapy for Spinal Muscular Atrophy (SMA) or at elucidating the basic pathophysiological processes of the disease. The overall goal of SMA Europe is to help the dedicated international scientific and medical community in its search for therapies for SMA. Time being critical for people with SMA, preferences will be given to projects that have the greatest potential to overcome barriers to translation of advances in basic science and to accelerate the identification of effective treatments. For more information please visit the SMA Europe web site
The ECD Global Alliance is soliciting Letters of Intent for funding of research projects focused on the study of Erdheim-Chester Disease
The Erdheim-Chester Disease Global Alliance is interested in receiving Letter of Intents for any study that can lead to an increase of knowledge related to the etiology, pathophysiology, diagnosis or treatment of Erdheim-Chester Disease. Upto a 100,000 USD will awarded to a maximum of 2 grants for projects that focus on areas that include development and implementation of an ECD patient registry, clinical trials related to treatment of ECD, improving the quality of life for ECD patients, simplifying diagnosis of ECD, understanding the pathobiology and molecular mechanisms of the disease. All investigation proposals will be considered and all qualified and interested investigators are encouraged to submit before 1 April, 2014.
For further information

DEBRA International research grants
This grant aims to
• Improve our 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
The deadlines for application submissions are normally twice per year, on 15th February or March and 15th September. Decisions on funding applications from these calls will normally be made in June and December, respectively.
However, details of calls and submission dates can vary from year to year, so always check this page

Call for proposals IFCAH 2014
This call for proposals, open to European groups, aimed to support research on Congenital Adrenal Hyperplasia (CAH). Specific topics that the proposals should focus on include: Increasing knowledge on pathophysiology of the disease, Prevention, diagnostic and treatment of natural or iatrogenic complications, Proposition of new therapeutic targets and protocols. Selected research projects will be supported up to EUR150k (total) and the funding period will not exceed three years. Funds will have to be used for expenses directly linked to the project, including specific equipment, operating costs or salaries of co-workers.

Applicants must hold an M.D., Ph.D., or equivalent academic degree and have a faculty position or equivalent at a college, university, medical school, or comparable institution. The projects submitted will be evaluated by international experts. Applications must be submitted no later than March 15th, 2014.. Specific forms for application can be obtained from cfp2014@ifcah.org.
For further details


Partnersearch, Job Opportunities
Group leader positions in the Imagine Institute of Genetic Diseases
The new Imagine Institute of Genetic Diseases, affiliated with the Necker Enfants maladies Hospital campus Paris, is inviting applications for group leader positions. Imagine is an interdisciplinary research center with excellent core facilities for genomics, cell imaging, flow cytometry, bioinformatics, pathophysiology and animal housing for transgenic mice and zebra fish. The new tailor-made building (to be opened in early January 2014) will offer cutting-edge research facilities. The Institute focuses on rare diseases, their genetic architecture and life-long outcomes. Imagine intends to address unmet basic and clinical research questions related to rare diseases, in order to increase knowledge in a major medical field that is currently insufficiently covered. This will result in the development of new biological concepts, diagnostic tools and innovative therapeutics. Applications can focus on any field directly linked or related to the basis, pathophysiology and treatment of genetic diseases, with special emphasis on:
1- Development, stem cells and neuroscience.
2- Computational biology and/or bioinformatics.
Applications in these two areas will be separately evaluated. Appointments will be made at a junior or senior level, depending on experience. Applications should be submitted to Professor Alain Fischer before May 15 2014 Further information can be found at
www.institutimagine.org or email

Head of the research unit for genodermatoses
DEBRA Austria seeks a head of the research unit at the EB House Austria, with specialisation in genodermatoses.
The ideal candidate will have the following qualifications
• Held/hold a leading position in a research setting for at least 5 years.
• A natural science and/or medical background and a record of research in the field of genodermatoses.
• Fulfil this position as an organisational lead of a research unit, including issues of staffing and finances.
• Experience and record in acquiring third-party funding is excellent.
• Familiar with basic research and translational aspects, and ready to bring promising therapeutic approaches further to the clinic.
• Take care of IP rights and exploitation issues, and to establish contact with an IP expert as counsel.
• Strong interest in sharing knowledge and ideas with colleagues and stakeholders from the scientific and rare disease community, and are willing to participate in relevant conferences and events.
• Bring across complex scientific matters to lay people – e.g. patients and their families – so they are able to understand the basic principles of your research.
Desirable qualities/ qualifications
• Experience with IP rights and technology exploitation are an asset.
• Preferably, you have experience in undertaking and leading on clinical studies. • A management degree is an asset.
TO APPLY Please send in your application by e-mail to office@debra-austria.org. Applications should include: Application letter, CV, Short outline of your field(s) of research, for a lay audience, Publications record. Please contact Dr. Rainer Riedl, chairman of DEBRA Austria, at +43-1-876 40 30-15 if you have any questions. Closing date: Monday, March 10th, 2014


Courses & Educational Initiatives
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 2014 course is now available. For Further details
5th ESO-SIOP Europe Masterclass in paediatric oncology
Date: 17-22 May 2014
Venue: Ljubljana, Slovenia

ESO and SIOP-Europe are pleased to announce the fifth Masterclass in Paediatric Oncology. This clinically-oriented educational programme has been designed for young paediatric oncologists who wish to improve their skills in clinical management of common childhood tumours. It is designed to offer a unique learning experience, providing practice-oriented training and the teaching sessions will focus on the application of the most recent research findings to clinical practice. Application deadline: 3 February 2014. Information, detailed programme and application form available at www.eso.net

radiz - Rare Disease Initiative Zurich
Date: 14-16 July 2014
Venue: Zurich, Switzerland

The 2nd radiz Rare Diseases Summer School will focus on a wide variety of subjects in the arena of rare diseases, from disease mechanisms and animal models, to improving diagnoses, to novel therapeutics. There will be lectures and workshops on drug development, model organisms, how to choose clinical endpoints, clinical trials, regulatory aspects, patient registries, patient initiatedresearch, ethical considerations, as well as what rare diseases may tell us about common diseases.
Further Information

Registration opens for joint EMA/FDA/MHLW-PMDA orphan medicinal product workshop
Registration is open for the third workshop on orphan product designation and grants jointly organised by the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), the Japanese Ministry of Health, Labour and Welfare (MHLW) and Pharmaceuticals and Medical Devices Agency (PMDA).
The event will be held on Monday 10 March 2014 at the EMA, London, United Kingdom.

The aim of the workshop is to provide information to companies as well as academics on the EMA, FDA and MHLW-PMDA systems for orphan medicinedesignation and on the grant programmes available for the development of orphan medicines. These programmes aim to promote the development of new medicines for the treatment of rare diseases.
Further Information


What's on Where?

Striving for Professionalism in investigator-initiated clinical trials
Date: 26-27 February; 2014
Venue: Brussels, Belgium

This workshop aims at bringing together investigators, academic organisations, hospital and university administration representatives, regulators, ethics committee members, lawyers, pharmaceutical companies, SMEs and patient representatives from different countries to learn about different approaches to sponsorship and public-private partnerships in conducting clinical trials in different countries. These multi-stakeholder discussions is intended to support professionalism in investigator-initiated trials (IITs) through working out recommendations for facilitating and harmonizing the framework and organisation for investigator-initiated clinical research.
For further information

EUROPLAN National Conferences Croatia
Date: 27-28 February, 2014
Venue: Zagreb, Croatia

Organised by the Croatian Alliance for Rare Diseases

EUROPLAN National Conferences Belgium
Date: 28 February 2014
Venue: Brussels, Belgium

Organised by Belgian National Alliance for Rare Diseases
For further details go to RaDiOrg.be

RE(ACT) Congress: 2nd International congress on research of rare and orphan diseases
Date: 5-8 March 2014
Venue: Basel, Switzerland

The conference sessions will explore issues and cutting-edge technologies that affect many adult and paediatric conditions. The following topics are to be discussed include Stem cell and cell therapy approaches, mapping diseases and genome instability, pathophysiology and diagnostics, bringing treatments to the clinic, degenerative disorders and research and patients.
For further information
Genomic Disorders 2014: The Genomics of Rare Diseases
Date: 5-7 March 2014
Venue: Cambridge, UK

Genomic Disorders 2014 will discuss the latest findings on the genomic basis of rare disorders as these can provide such powerful insights into human biology. The meeting will focus on how human genome analysis can best assist future clinical practice and patient care. A particular emphasis of this year’s meeting will be on genomics in reproductive medicine, modelling rare disorders in animal models and cells, and interpreting genomic variants in rare diseases.
For further information

The 9th International Congress on Autoimmunity
Date: 26-30 March 2014
Venue: Nice, France

This is a prominent conference with experts in immunology, rheumatology and related fields participating. The congress will address the genetic, etiology, diagnostic, clinical aspects and novel therapies of 80 autoimmune diseases.
For further details

Gene, Cell and Molecular Therapies for Inherited Metabolic Disease
Date: 27 March 2014
Venue: London, UK

The aim of this meeting is to establish and encourage a closer interface between clinicians and scientists with the goal of translating gene therapy and novel technologies into clinical treatment of inherited metabolic disorders to UK patients at the earliest opportunity.
For further information

2014 Lymphangioleiomyomatosis International Research Conference
Date: 28-30 March 2014
Venue: Chicago, USA

The LAM Foundation will be holding its 17 Annual International Lymphangioleiomyomatosis Research Conference and Patient & Family Educational Symposium on March 28 - 30 in Chicago, IL, USA. Save the date for this informative conference
For further details

International Meeting on Fibrodysplasia Ossificans Progressiva, 2014
Date: 4-5 April 2014
Venue: Genova, Italy

The 8th International Meeting on Fibrodysplasia Ossificans Progressiva (FOP) organized by the FOP Italia Association will take place in Genova with the participation of scientists from European and American countries who will discuss pathogenic mechanisms of FOP as possible targets for treatments. Representatives of patients associations from several countries and individual patients and families will also participate.
For further information go to fopilatia.it or www.cisef.org

7th European Conference on Rare Diseases & Orphan Products (ECRD 2014)
Date: 8-10 May 2014
Venue: Berlin, Germany

The European Conference on Rare Diseases & Orphan Products (ECRD) promises to be an enlightening forum for rare disease stakeholders across various disciplines across in European countries. It aims to cover research, development of new treatments, healthcare, social care, information, public health and support. For further details

EUROPLAN National Conferences Spain
Date: 6 June 2014
Venue: Madrid, Spain

Organised by FEDER; the Spanish Alliance for Rare Diseases

LGDA Patient – Family Conference
Date: 13-14 June 2014
Venue: Texas, U.S.

"The Lymphangiomatosis & Gorham's Disease Alliance (LGDA) will hold its inaugural Patient - Family Conference. This milestone event will bring patients, families, and experts in the field from around the world together for the very first time on June 13 & 14, 2014, at the Sheraton Suites Market Center in Dallas, Texas, U.S. For details about the conference visit the website.

Euromit 2014 - International Meeting on Mitochondrial Pathology
Date: 15–19 June, 2014
Location: Tampere, Finland

Euromit 2014 will be the 9th in a series of international conferences dedicated to understanding mitochondrial disease. The conference will bring together leaders of the field as well as many young talents. The organisers expect that around 700 molecular scientists, clinicians and representatives of the healthcare industry to attend.
For further information

13th International Congress on Neuromuscular Diseases - ICNMD 2014
Date: 5-11 July 2014
Venue: Marseille, France

The XIII ICNMD experts will come together to share knowledge and experiences in the field of neuromuscular diseases. Physicians and scientists, involved in the diagnosis and care to the most updated research in basic mechanisms and therapeutic approaches in the theme will greatly benefit. For further details

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

The conference will provide high quality contributions on a wide range of topics including clinical innovations, genetics and basic science. Update on new therapeutic strategies will be presented and challenging issues will be discussed. They have planned to invite distinguished lecturers notably in the field of innate immunity.
For further information

3rd International Conference on Immune Tolerance 2014
Date: 28th - 30th 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

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

The meeting will bring together high-profile scientists from around the world and will focus on how basic science on rare diseases can have an impact for the development of novel therapeutic strategies. This conference will bring together a number of high profile speakers active in the field of rare disease research and translational medicine.
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. There is presently no known cure for Batten disease
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 which was attended by 400 participants. The congress will be a two-day programme and is opened to all stakeholders with an interest in the clinical management of primary immunodeficiencies (PIDs).
For Further Information

Commercial events

2nd Orphan Drugs Research & Commercialization Conference
Date: 20-21 February 2014
Venue: San Diego, U.S.

This meeting provides a forum for all stakeholders, from researchers, industry leaders, patient advocacy organizations, and regulatory experts to gather and share different perspectives on how to best guide the field forward. The program will include presentations on the latest scientific research, such as RNAi therapeutics and gene therapy; pricing and reimbursement challenges; clinical endpoints; and much more.
For Further Information

Cell & Gene Therapy Conference
Date: 20-21 February 2014
Venue: San Diego, U.S.

This meeting will discuss the evolving regulatory challenges and pre-clinical requirements, the development and applications of cell and gene therapy, immune responses, as well as business models and commercial milestones.
For further information

The Commercialisation of Orphan & Rare Disease Drugs 2014
Date: 20–21 March, 2014
Venue: London, UK

This forum provides a unique opportunity to meet, network and hear from acknowledged industry experts. Discover untapped revenue streams in the blockbuster market - increase your bottom line and ensure the commercial success of your organisation. Explore the latest trends in pricing and reimbursement, and more importantly what lies beyond – from optimal business models to improving your marketing and sales strategy.
For further information

World Orphan Drug Congress USA
Date: 23 – 25 April, 2014 Venue: Washington D.C., U.S. The 4th annual World Orphan Drug Congress USA is dedicated to fostering partnerships and collaboration. It is about expediting orphan drug development and articulating its value, from discovery to patient access, so that manufacturers are guaranteed full and speedy reimbursement.
For Further Information

Stem Cell Commercialization & Partnering Conference
Date: 23–25 April, 2014
Venue: Boston, U.S

This forum presents information regarding cutting-edge developments in all areas of stem cell research including the biology, medicine, applications, regulations and business of stem cells. This track focuses on the business opportunities, challenges and potential strategies for overcoming them.
For further information

9th World Stem Cells & Regenerative Medicine Congress
Date: 20–22 May, 2014 Location: London, UK In this event pharma, biotech, academia and investors join together and which is a medium for biotechs and academia to get their research noticed.
For further information

The World Orphan Drug Congress Asia 2014
Date: 10-11 June 2014
Venue: Singapore

The World Orphan Drug Congress Asia 2014 focuses on fostering partnerships and relationships between industry, governments, payers, investors and patients as well as to expedite orphan drug development and articulating its value, from discovery to clinical development, to license, to manufacturing, to launch and to sustainability of supply, so that manufacturers are guaranteed full and speedy reimbursement.
For Further Information


Orphanews International, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews International 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: Divya Unni
Editors for Scientific Content: Catherine Pouzat, Sophie Höhn
Contact Us
Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Barbara Cagniard, Virginie Hivert, Helena Kaariainen, Odile Kremp, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Jaroslaw Waligora

EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Rumen Stefanov (Bulgaria), Ivo Baric (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek Jr. (Czech Republic), Marianne Jespersen (Denmark), Inna Vabamae (Estonia), Helena Kaariainen (Finland), Alain Garcia (France), Birgit Schnieders (Germany), Christos Katamis (Greece), Janos Sandor (Hungary), Thor Thorarinsson (Iceland) , John Devlin (Ireland), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Romalda Baranauskiene (Lithuania) , Yolande Wagener (Luxembourg), Miriam Dalmas (Malta), Jolande Huizer (Netherlands), Stein Are Aksnes (Norway), To be nominated (Poland), Alexandre Diniz (Portugal), Emilia Severin (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Isabel Pena-Rey (Spain), To be nominated (Sweden) , Sabina Gallati (Switzerland), Edmund Jessop (UK)
EUCERD ECDC Representative: Andrew Amato
EUCERD Patient Organisation Representatives: Dorica Dan, Yann Le Cam, Christel Nourissier, Bianca Pizzera
EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolène Aymé, Jean Donadieu, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Gerard Wagemaker
EUCERD European Commission Participants: Catherine Berens, Iiro Eerola, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Jaroslaw Waligora, Antoni Montserrat Moliner, Michael Huebel, Bruno Sepodes (EMA-COMP)

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), Zsuzsanna Lengyel (Hungary), Andrew Green (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)
For more information on the European Union Committee of Experts on Rare Diseases
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