29 April 2014 print
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RNAi lost and found in translation: a breakthrough therapeutic area

Nature Biotechonology has recently reported on the progress industry is making in understanding the benefits of RNAi as a treatment modality, news that is especially promising for rare diseases patients. RNAi is a part of the “gene silencing” technology where the introduction of small strands of RNA (20-24 base pairs) binds to its complementary RNA in vivo, forming a double stranded RNA stopping the protein formation of that RNA.

While this methodology has been successfully tried and tested in fundamental research, its foray into clinical research has been markedly sketchy. The authors describe how start-ups were developing therapeutic platforms using this technology and big pharma followed suit, which unfortunately, did not bear fruit. However, the initial setbacks were tempered by recent success of Alnylam in using RNAi –with effective delivery vehicle to the liver – in not only knocking down target genes but also causing a therapeutic effect in humans, has been good news for patients suffering from rare liver diseases. The authors present how Alnylam is now courted by Genzyme boosting its ability to bring this therapy to the market a possible dream. The article also describes the case of fellow RNAi specialist Dicerna, who has also netted $USD 92.9 million in an IPO encouraged by the success of Alnylam.

According to the authors, these ventures into newer and advanced methodologies to treat diseases, by looking beyond conventional drugs is the sign of times to come as “companies pursue gene therapy, gene editing and protein misfolding correction, to name a few, are reminding investors of what it was like in the genomics era, to dare to imagine transformative advances”.
Access the article through the journal

EU Policy News
Report on the application of the Regulation (EC) No 1394/2007 on Advanced Therapy Medicinal Products

The European Commission has adopted a Report on the application of the Regulation (EC) No 1394/2007 on Advanced Therapy Medicinal Products (ATMP). In the report, the Commission takes stock of the situation of advanced therapy medicinal products in the EU and has amended the Directive to provide an efficient approach in an effort to advance the development of ATMPs.

The EU has recognised the potential of advanced therapies for a range of population with unmet needs. To provide for a common framework for the marketing of ATMPs, Regulation (EC) No 1394/2007 of the European Parliament and of the Council on ATMP Regulation was adopted in 2007. Due to the strenuousness to bring ATMP’s into the market, a public consultation was issued, the results of which led to the amendment of the Directive 2001/83/EC and Regulation (EC) No 726/2004. The amendments include an increased clarification of the scope of the ATMP regulation, avoiding disparities in the classification of ATMPs in the EU. Clarification of the conditions for the application of the hospital exemption, as well as the role of data obtained in the context of marketing authorisation procedures is expected. The Directive also calls for revising the requirements for the authorisation of ATMPs with a view to ensure that applicable requirements are proportionate and well-adapted to the specific characteristics, where streamlining the marketing authorisation procedures as well as extending the certification procedure and clarification of the link between the certification and the marketing authorisation procedure is highlighter. Also in the Directive is a push towards creating a more favourable environment for ATMP developers working in an academic or non-for-profit setting, including by promoting early contacts with the authorities through the application of the fee reduction for scientific advice and by extending the certification scheme to these developers. The Directive invites considering possible fee incentives to reduce the financial impact of post-marketing obligations.
Read the Directive
EU moves towards increasing clinical trial transperancy
Under a draft law unanimously agreed with EU ministers and passed by Parliament on 2 April, 2014, pharmaceutical companies and academic researchers will have to post the results of all their European clinical trials in a publicly-accessible database. According to this law, which is part of the continuous effort to increase transparency, researchers who perform clinical trials in the European Union will have to make the results public. These trials must be registered in a central database and a summary of results— positive or negative—must be uploaded within 1 year after the end of the trial. In addition, researchers must release a full clinical study report containing detailed information about the trial design and analysis, including patient-level data sets, if the medicine is submitted for marketing authorisation, irrespective of that application's success. This piece of legislation is expected to come into force in mid-2016 and the EU will fine non-compliant academic researchers and companies. Other aspects of the law include facilitation of cross-border cooperation to make clinical trials larger, more viable and more reliable, which should in turn boost efforts to develop treatments for rare diseases.
For further information

EMA surging ahead with schemes to help rare disease patients
Several initiatives were announced by the European Medicines Agency in April 2014 that will prove to be advantageous to rare disease stakeholders

European Medicines Agency introduces new fee incentives for SMEs for post-authorisation activities
The EMA has announced an increase in fees payable by applicants and marketing-authorisation holders to increase by 1.5% on 1 April 2014 to account for inflation, at the same time they have introduced new post-authorisation fee incentives to support micro, small and medium-sized enterprises (SMEs). More than 60% of orphan medicinal products (OMP's) were developed by SME’s between 2010-2012, as they have been in the forefront of developing innovative medications. Thus these incentives is viewed as favourable news for patients suffering from rare diseases as it lowers costs for cash-strapped SME's and speeds up market entry for OMPs. SME’s had previously raised concerns about the increase in fees (See Orphanews for article) and this announcement may allay the disquiet among them. The incentives include a 100% fee reduction for micro-sized companies, a 40% reduction for small and medium-sized enterprises. Other kinds of support that are already provided by the EMA for SME’s include fee reductions for scientific advice throughout the medicine’s lifecycle, outreach programmes and dedicated newsletters.
Read the EMA press release

EMA and Australian regulators collaborate to accelerate access to orphan drugs

In an exceedingly collaborative move that will profit rare disease patients in the European Union and Australia, the European Medicines Agency (EMA) and the Australian Therapeutic Goods Administration (TGA) will organise the sharing of the workload for marketing-authorisation applications of orphan drugs, as well as the possibility of scientific exchange to facilitate the evaluation of such medicines. They will be sharing full assessment reports related to marketing authorisations of orphan drug which promises to be economical in terms of time and resource. This move endorses parallel submissions by sponsors to EMA and TGA, even though both regulators will independently decide over the suitability of each medicine to be authorised in their respective markets.
Read the EMA press release

EMA takes its cue from the European Parliament to increase transparency
The European Medicines Agency (EMA) has confirmed that AbbVie has withdrawn both its court cases brought against the Agency on access to clinical-trial data, although the case brought by InterMune is ongoing (Read the OrphaNews article). AbbVie requested EMA to consider an entirely new set of redacted documents along with justification for the redaction proposed by the company. EMA responded positively affirming that that the redactions proposed by AbbVie were limited and compatible with EMA's practices. This led to AbbVie accepting the new set of documents and thus dropping the case.
Read the EMA press release
In related news, as the new Clinical Trials Regulation was overwhelmingly voted in favour of releasing clinical trial data in the European Parliament on 2 April 2014 (See above), the European Medicines Agency has also announced its move towards increased transparency by maneuvering the release of clinical trial reports. The Agency has announced that they will be providing targeted discussions on how they will set the principles for the possible redaction of the clinical study reports to be published. These discussions will decide the criteria for redacting commercially sensitive material and provide clarifications on consulations with the clinical trial data-owners on these redactions. The Agency will liaise shortly with organisations representing patients, academia, pharmaceutical industry, as well as European Union (EU) institutions.
Read the EMA press release
Adaptive licensing: EMA pilot project
The Agency has also announced the launch of an adaptive licensing pilot project, which is a reflective stride towards understanding a different approach to marketing authorisation of specialised drugs which will benefit therapeutics that do not follow the conventional format, such as advanced therapeutics and/or medications for rare diseases.

Adaptive licensing is defined as a "prospectively planned, adaptive approach to bringing drugs to market, characterised by flexibility and an iterative process of evidence gathering". Currently there is an urgent need to explore how the regulatory processes and healthcare systems can be used to support research and development whilst collecting the data that is necessary to confirm the clinical profile of a product and thus support patient access to medications, such as orphan medicinal products (OMP’s) that offer acceptable safety and effectiveness. The adaptive licensing process conceptualised by EMA differs from traditional dichotomous license decisions where the presumption is that an experimental therapy, on receiving a license, is safe and efficacious for use in a given patient population. The Agency envisions the adaptive licensing process to be a graded, tightly-managed market entry, to account for higher risk and uncertainties than that involved in the conventional licensing paradigm.

To better comprehend the risks and challenges that might be associated with this process, EMA is inviting companies to participate in its adaptive licensing pilot project by submitting ongoing medicine development programmes for consideration as prospective adaptive licencing pilot cases. The experimental drugs or biologicals called “live assets” by the EMA should be in the early stage of clinical development, which is prior to initiation of phase II studies so as to enable “actionable input from stakeholders into the planning of the development, licensing, monitoring, reimbursement and utilisation pathways”. To make this possible, commitment-free discussions about the “live asset” will involve EU payers (or HTA bodies which advise payers) and, whenever possible, patients groups and provider groups to obtain an overall picture in the earliest developmental stage of the medication that is possible. Although the Agency warns that these discussions will be exploratory and not formal ‘Scientific Advice’ sessions, their therapeutic may have to opportunity to progress to more formal sessions.

The Agency envisages this pilot project as the building block to better understand this alternative process, and as it evolves the European Commission will “examine the legal and policy aspects related to adaptive licensing in collaboration with the EU Member States and by consultation with relevant stakeholders, as necessary”.
For further information or to initiate a pilot case, please contact adaptivelicensing@ema.europa.eu
Read EMA press release

All the above initiatives builds on the already existing regulatory processes that are set up at the EMA to ascertain that safe and effective OMP’s reach the patients in a timely manner.


National & International Policy Developments
Other International News
Pharmaceutical Management Agency of New Zealand seeks feedback on new rare disease fund
Pharmaceutical Management Agency (Pharmac) is seeking public feedback on a new funding approach specifically geared for high-cost medicines for rare disorders. The use of a contestable fund, worth an estimated $NZD 5 million a year, will be tested this year. According to the discussion document on the new funding model, the $5 million contestable fund will be sourced from savings made through the Named Patient Pharmaceutical Assessment pathway. Because the contestable fund is already capped, it won't limit Pharmac's ability to fund other treatments for less rare conditions. Once the details are ironed out, Pharmac anticipates receiving proposals from pharmaceutical companies by the end of 2014 and funding could begin early next year. However, New Zealand Organisation of Rare Diseases (NZORD) notes that $NZD 5 million budget is not enough, considering that an estimated between $NZD 20 and 25 million may be needed to give all patients with rare diseases the drugs they need. NZORD also finds the timing of the announcement prior to this year's election is also "a cause for suspicion".
Go to the Pharmac website
In related news, rare disease patients in New Zealand accuse Pharmac of failing to listen to the patients' and advocates' concerns, and welcome the opportunity to address Pharmac in person about their issues with the proposed decision criteria. NZORD wants Pharmac to soften their hard line of sticking primarily to economic factors as that approach contradicts so many important documents such as the guidance of International Covenants, NZ's Public Health and Disability Act, the NZ Medicines Strategy, and the moral frameworks that are central to the New Zealand health system.
Go to the NZORD website

PCORI of US announces expert panel on rare disease
The Patient-Centered Outcomes Research Institute (PCORI), authorised by the US Congress to conduct research to provide information about the best available evidence to help patients and their health care providers make more informed decisions has approved 13 people as members of PCORI’s new Advisory Panel on Rare Disease. The diverse group of panelists will apply their experience and expertise to advising PCORI on its research priorities in the area of rare disease, as well as on engaging with the rare disease research community. The new panelists represent a range of stakeholder groups and perspectives, including people with rare diseases, family caregivers, clinicians, drug and device makers, and researchers, among others with more than a third representing patients and patient advocates. The panel will assist PCORI in identifying experts to serve on ad hoc advisory panels as needed to consider research issues related to particular rare diseases to advice the US Congress.
For further information on PCORI

Guidance Documents and Recommendations
Constitutional mismatch repair deficiency syndrome: guidelines for surveillance of patients proposed by the European Consortium “Care for CMMR-D”
Consult the Pubmed abstract
To read more about "Constitutional mismatch repair deficiency syndrome"

J Med Genet. ; 51(5):283-93 ; May 2014
Classical Hodgkin lymphoma: guidelines for the first line management
Consult the Pubmed abstract
To read more about "Hodgkin lymphoma, classical"

Br J Haematol. ; [Epub ahead of print] ; April 2014
Acromegaly: a consensus on the medical treatment
Consult the Pubmed abstract
To read more about "Acromegaly"

Nat Rev Endocrinol. ; 10(4):243-8 ; April 2014
Bioinformatics, Registries and Data Management
Veneto Region’s rare diseases registry provides epidemiological data on rare diseases
An article published in Orphanet Journal of Rare Diseases presents the results of a study conducted at population level using the Veneto Regions rare disease registry to collect epidemiological data on rare diseases from the years 2002-2012. This has been the first known study on the prevalence of rare diseases at the population level. The authors describe the shortcomings of population registries focusing on single rare diseases as they do not provide a broad picture of rare diseases. The authors depict this database as a multi source web-based information system that combines aspects of population-based as well as clinically oriented registry which was introduced in the Veneto region in 2002 and subsequently adopted in 6 other Italian regions. From studying the data already collected, the authors were able to provide the first indication of the magnitude of the public health problem associated with rare diseases.

The authors observed that 1 in 3 rare disease patients belonged to the paediatric population where the most common diseases were congenital malformations, hematological diseases and inherited metabolic diseases. Also enlightening from the study was the high rate of survival into adulthood. The rare diseases suffered by the adults were mostly eye disorders but also included a population of patients suffering from rare neurological diseases, where ALS accounted for high fatality for half the deaths. From the data obtained from the registry, the authors extrapolated that “between 6,500,000 and 9,880,000 people living in the EU28 countries have a rare disease, which corresponds to 1.3%-2% of the whole population”, a number much lower than the estimated 6-8%. However, they attribute the lower number to some of the limitations of the registry. The authors believe that this study helps in justifying resource allocation and addressing the health care needs of the rare disease patients.
Read the open access article
The Developmental Brain Disorders Database

A brand new database that references the ontology of developmental brain phenotypes has been described in an article published in American Journal of Medical Genetics Part A. This database is called the
Developmental Brain Disorders Database (DBDB) is a “publicly available, online-curated repository of genes, phenotypes, and syndromes associated with neurodevelopmental disorders”. According to the authors, this database uses a novel system of levels of evidence for gene-phenotype associations that will assist clinicians to correctly identify neurodevelopmental phenotypes, recognise syndromes, as well as prioritise the best candidate for genetic testing in addition to providing researchers efficiently documented source of genes against which research sequencing results can be compared in addition to providing innovative observations about the landscape of the neurogenetics knowledge base.

Phenotype definitions in DBDD are drawn from the Medical Subject Headings controlled thesaurus (MeSH), the Human Phenotype Ontology, peer-reviewed publications indexed in PubMed, as well as key textbooks in neuroradiology, medical genetics, and epilepsy.

The authors believe that this database DBDB will streamline the understanding of neurodevelopmental disorders when used with existing web-based resources such as OMIM and GeneReviews by introducing levels of evidence for gene-phenotype associations and a structured ontology of neurodevelopmental disorders. The authors also highlight the user-friendly nature of this easily updatable database as well as its ability to provide consistency in the terms used for phenotypes. DBDB is hosted at the University of Rochester Medical Center.
Consult the Pubmed abstract

An InSiGHT into gene variants in Lynch syndrome
Clinical classification of hereditary sequence variants identified in disease-associated genes directly affects clinical management of affected individuals and their relatives. An article published in Nature Genetics describes a collaborative research study spearheaded by the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to develop, test and apply a standardised classification scheme to constitutional variants mismatch repair genes (MMR) causing Lynch syndrome. InSiGHT is an international multidisciplinary, scientific organisation whose efforts are directed towards improving the quality of care of patients as well as the quality of life of families with any condition resulting in hereditary gastrointestinal tumours. For this study, MMR gene variants submitted to the locus specific database (LSDB) were reviewed by an international panel consisting multidisciplinary experts of the clinical and functional data available for variants. This InSiGHT Variant Interpretation Committee (VIC) has outlined the criteria developed through these submissions, which provides a basis for the standardised clinical classification of variants to inform patient and family management through genetic counselling. The authors report that through this initiative, the systematic evaluation of 2,360 constitutional variants has been possible, which will benefit thousands of families internationally.

According to the authors “this initiative shows how clas¬sification may be assisted by promoting standardized data submission from stakeholders in the clinical and research settings, thereby allow¬ing access to unpublished clinical and functional information used to facilitate variant classification (and) provide a key model of LSDB-centric multidisciplinary collaboration for the transparent interpretation of DNA variants”.
Consult the Pubmed abstract


Ethical, Legal & Social Issues
The rising voice of rare disease patients
A recent article on health policy highlights the importance of patient and patient organisation involvement in decision-making concerning the evaluation and authorisation of medicinal products for rare diseases.

In this April’s issue of the Regulatory Rapporteur, authors Maria Mavris (Therapeutic Development Director) and Yann Le Cam (CEO, European Organisation for Rare Diseases, EURORDIS) demonstrate how efforts from both the European Medicines Agency (EMA) and EURORDIS to interact more closely have increased transparency and awareness of rare disease treatment research and development.

Founded in 1997, EURORDIS now represents over 600 patient associations from 58 countries. The organisation has provided increasing patient support and successfully raised awareness about rare diseases, through various initiatives such as Rare Disease Day, the European Conference on Rare Disease and Orphan Products (ECRD), the Rare Disease Day Policy Event and other workshops for patient organisations on Orphan Medicinal Products.

Through its continuous interaction with the EMA, EURORDIS acts as advocate for EU regulation on orphan treatments. Patients have become directly involved in making recommendations on orphan drug designation and health policy decisions. Furthermore, in the past three years, the EMA and EURORDIS have improved patient involvement and transparency through publication of documents and clinical trials.

Such efforts represent a great improvement in patient involvement and stakeholder interaction. Policy must, however, be strengthened further in order to ensure protection of all parties involved, from patient identity to conflicts of interest regarding research funding.
Read the abstract

A case for conducting genomic and clinical data sharing within the human rights framework
An article published in Human Genetics makes a case for positioning genomic and clinical data sharing within a human rights framework. The authors believe that while collaboration for data sharing is increasingly embraced by policymakers and the international biomedical community, there is a lack of common ethical and legal framework to connect regulators, funders, consortia, and research projects. The authors recommend an international code of conduct nestled within the human rights framework to provide accountability in the age of global genomic and clinical data sharing.

The authors have identified key obstacles that can be detrimental to data sharing in the current times which include lack of policy harmonization, lack of structural support, legal and ethical hurdles and cultural and behavioural differences. The authors believe that these obstacles can be overcome by a human rights approach as it has both political and legal dimensions, reaching beyond the moral appeals of bioethics and can provide a more robust governance framework for the regulation of genomics research. Another benefit is that human rights belong to individuals and groups and can distinguish between data sharing and privacy concerns. Additionally it can foster responsible translational genomic research by offering stronger protection in three critical areas: privacy; anti-discrimination and fair access; and procedural fairness.

The authors believe that even though there may be concerns and objections to a human rights framework, the benefits far outweigh the concerns. Finally, the authors themselves intend to engage stakeholders in co-designing this code and encourage questions as well as concerns to be sent to them to work on this “important policymaking project”. Contact edward.dove@mcgill.ca, or bartha.knoppers@mcgill.ca
Consult the Pubmed abstract


New Syndromes

GLOW syndrome is caused by mutations in the RNase IIIb domain of DICER1
The authors reported a novel syndrome termed GLOW, an acronym for its core phenotypic findings, which include Global developmental delay, Lung cysts, Overgrowth and Wilms tumour caused by mutations in the RNase IIIb domain of DICER1.
Consult the Pubmed abstract

J Med Genet. ; 51(5):294-302 ; March 2014
X-linked intellectual disability due to ZMYM3 and SYP mutations in Finnish families
The authors identified one missense mutation in the candidate gene ZMYM3 in three affected Finnish males with a previously unrecognized syndrome of intellectual disability characterized by unique facial features, aortic stenosis and hypospadias. In addition, a previously reported benign variant in SYP was identified in a large Finnish family with nine affected males in three generations, who have a syndromic phenotype.
Consult the Pubmed abstract

Orphanet J Rare Dis. ; 9(1):49 ; April 2014
Microdeletions involving 15q22.2: NARG2 and RORA may be responsible for neurological symptoms observed in patients with deletions in this region
The authors collected genotype and phenotype data from five patients with microdeletions involving 15q22.2. Intellectual disability and epilepsy were frequently observed in those patients. Genotype-phenotype correlation analysis narrowed the critical region for such neurologic symptoms to a genomic region including NARG2 and RORA.
Consult the Pubmed abstract

Eur J Med Genet. ; 57(4):163-8 ; March 2014

New Genes

Congenital heart defects in humans caused by rare variants in NR2F2
Consult the Pubmed abstract
To read more about "Atrioventricular canal defect"
To read more about "Congenital aortic valve stenosis"
To read more about "Tetralogy of Fallot"
To read more about "Hypoplastic left heart syndrome"
To read more about "Aorta coarctation"

Am J Hum Genet. ; 94(4):574-85 ; April 2014
Simplified gyral patterning and infantile-onset epilepsy in two unrelated individuals due to de novo mutations in TUBB2A
Consult the Pubmed abstract
Am J Hum Genet. ; 94(4):634-41 ; April 2014
TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function
Consult the Pubmed abstract
Nat Genet. ; Epub ahead of print ; March 2014
Spectrum of human diseases phenotypes associated with up-regulated type I interferon signalling caused by gain-of-function mutations in IFIH1
Consult the Pubmed abstract
To read more about "Aicardi-Goutières syndrome"
To read more about "Hereditary spastic paraplegia"

Nat Genet. ; Epub ahead of print ; March 2014
Megalencephaly-polymicrogyria-postaxial polydactyly–hydrocephalus syndrome due to de novo CCND2 mutations
Consult the Pubmed abstract
To read more about "Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus"

Nat Genet. ; Epub ahead of print ; April 2014
Predisposition to familial cutaneous malignant melanoma associated to missense loss-of-function variants in POT1
Consult the Pubmed abstracts
To read more about "Familial melanoma"

Nat Genet. ; Epub ahead of print ; March 2014
Small cell carcinoma of the ovary is characterized by recurrent mutations in SMARCA4
Consult the Pubmed abstracts
To read more about "Small cell carcinoma of the ovary"

Nat Genet. ; [Epub ahead of print] ; March 2014
Chrondromyxoid fibroma development linked to GRM1
Consult the Pubmed abstract
Nat Genet. ; [Epub ahead of print] ; March 2014
Severe arthrogryposis multiplex congenital with axoglial defects due to mutations in CNTNAP1 and ADCY6
Consult the Pubmed abstract
To read more about "Arthrogryposis multiplex congenita"

Hum Mol Genet. ; 23(9):2279-89 ; May 2014
EDS/myopathy overlap syndrome and Bethlem myopathy caused by mutations in COL12A1
Consult the Pubmed abstracts
To read more about "Bethlem myopathy"

Hum Mol Genet. ; 23(9):2339-52; 2353-63 ; May 2014
The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and modulates endolysosomal function
Consult the Pubmed abstract
Hum Mol Genet. ; 23(9):2428-39 ; May 2014
Predisposition to hereditary malignant pheochromocytoma-paraganglioma is associated to germline mutations in FH
Consult the Pubmed abstract
To read more about "Hereditary pheochromocytoma-paraganglioma"

Hum Mol Genet. ; 23(9):2440-6 ; May 2014
Isolated polycystic liver disease due to LRP5 mutations
Consult the Pubmed abstract
To read more about "Isolated polycystic liver disease"

Proc Natl Acad Sci U S A. ; 111(14):5343-8 ; April 2014
Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation
Consult the Pubmed abstract
Hum Mol Genet. ; [Epub ahead of print] ; February 2014
Metaphyseal chondrodysplasia, Spahr type, caused by MMP13 mutations
Consult the Pubmed abstract
To read more about "Metaphyseal chondrodysplasia, Spahr type"

Am J Med Genet A. ; 164(5):1175-9 ; May 2014
Progressive cerebello-cerebral atrophy type 2 due to VPS53 mutations
Consult the Pubmed abstract
To read more about "Progressive cerebello-cerebral atrophy"

J Med Genet. ; 51(5):303-8 ; May 2014
Two novel genetic causes of Dravet syndrome: GABRA1 in four cases and STXBP1 in three cases
Consult the Pubmed abstract
To read more about "Dravet syndrome"

Neurology ; 82(14):1245-53 ; April 2014
One case of spinal muscular atrophy with respiratory distress phenotype due to a mutation in LAS1L
Consult the Pubmed abstract
To read more about "Spinal muscular atrophy with respiratory distress"

Neurology ; 82(15):1322-30 ; April 2014
Increased risk of developing acute lymphoblastic leukemia for individuals born with the translocation between chromosome 15 and 21 compared to the general population
Consult the Pubmed abstract
To read more about "Acute lymphoblastic leukemia"

Nature ; 508(7494):98-102 ; April 2014

Research in Action

Clinical Research
WHIM syndrome: the CXCR4 antagonist plerixafor increases circulating leucocytes, decreases infections, but does not fully restore immunoglobulin levels
Consult the Pubmed abstract
To read more about "WHIM syndrome"

Blood ; 123(15):2308-16 ; April 2014
Acromegaly: primary treatment with lanreotide provides early and sustained reduction in GH-secreting macroadenomas volume and improves quality of life
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Acromegaly"

J Clin Endocrinol Metab. ; 99(4):1282-90 ; April 2014
Diffuse intrinsic pontine glioma: identification of recurrent activating ACVR1 mutations
Consult the Pubmed abstracts
To read more about "Astrocytoma"
To read more about "High-grade astrocytoma"

Nat Genet. ; [Epub ahead of print] ; April 2014
PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome
Consult the Pubmed abstract
To read more about "Hypotonia - cystinuria syndrome"

Neurology ; 82(14):1254-60 ; April 2014
Severe congenital neutropenia: detection of RUNX1 and CSF3R mutations could be used as a marker for identifying a high risk of progressing to leukemias or myelodysplastic syndrome
Consult the Pubmed abstract
To read more about "Severe congenital neutropenia"

Blood ; 123(14):2229-37 ; April 2014
Gene Therapy
Friedreich ataxia: adeno-associated virus rh10 vector expressing human FXN fully prevented the onset of cardiac disease and was able to reverse the cardiomyopathy in model mice
Consult the Pubmed abstract
To read more about "Friedreich ataxia"

Nat Med. ; [Epub ahead of print] ; April 2014
Therapeutic Approaches

Beta-thalassemia: RAP-011, an activin receptor IIA ligand trap, may have therapeutic relevance by suppressing the deleterious effects of GDF11 in mice
Consult the Pubmed abstract
To read more about "Beta-thalassemia"
To read more about "Beta-thalassemia intermedia"

Nat Med. ; 20(4):398-407 ; April 2014
Myelodysplastic syndromes: the ligand-trapping fusion protein ACE-536 as a new potential treatment for anemia, including that caused by ineffective erythropoeisis
Consult the Pubmed abstract
To read more about "Myelodysplastic syndromes"

Nat Med. ; 20(4):408-14 ; April 2014
Huntington disease: an oral therapy with FTY720 (fingolimod) improved motor function, prolonged survival and reduced brain atrophy in R6/2 mice
Consult the Pubmed abstract
To read more about "Huntington disease"

Hum Mol Genet. ; 23(9):2251-65 ; May 2014
Amelogenesis imperfecta: 4-phenylbutyrate can rescue the enamel phenotype in affected female mice offering a potential therapeutic option
Consult the Pubmed abstract

To read more about "Hypomaturation amelogenesis imperfecta"
To read more about "Amelogenesis imperfecta"

Hum Mol Genet. ; 23(9):2468-80 ; May 2014
Embryonal rhabdomyosarcoma: glycogen synthase kinase 3 inhibitors induce the canonical WNT/β pathway to suppress growth and self-renewal
Consult the Pubmed abstract

To read more about "Embryonal rhabdomyosarcoma"

Proc Natl Acad Sci U S A. ; 111(14):5349-54 ; April 2014
Glial tumor: amphotericin B enhances the microglial reduction of brain tumor initiating cells spheres in mice
Consult the Pubmed abstract
To read more about "Glial tumor"

Nat Neurosci. ; 17(1):46-55 ; January 2014
Neurofibromatosis type 2 (NF2): mTORC1 inhibitor rapamycin reduces the severity of NF2-related Schwann cell tumorigenesis without significant toxicity
Consult the Pubmed abstract
To read more about "Neurofibromatosis type 2"

Neuro Oncol. ; 16(4):493-504 ; April 2014
Hereditary hyperekplexia: DH-CBD, a non-psychoactive cannabinoid, can rescue glycine receptors functional deficiency and exaggerated acoustic and tactile startle responses in mice
Consult the Pubmed abstract
To read more about "Hereditary hyperekplexia"

Nat Neurosci. ; 17(2):232-9 ; February 2014
Mitochondrial diseases: mitochondrially addressed RNAs targeting a pathogenic point mutation in mtDNA induce a decrease of mtDNA bearing a pathogenic point mutation in ND5
Consult the Pubmed abstract
J Biol Chem. ; [Epub ahead of print] ; April 2014
GM1 gangliosidosis: adeno-associated viral vector carrying the therapeutic gene injected bilaterally into two brain regions of a cat model demonstrated normalization of disease
Consult the Pubmed abstract
To read more about "GM1 gangliosidosis"

Sci Transl Med. ; 6(231):231ra48 ; April 2014
Diagnostic Approaches

Metabolic evaluation of the child with an intellectual developmental disorder: diagnostic algorithm for identification of treatable causes and new digital resources
Consult the Pubmed abstract
To read more about "Rare intellectual disability with developmental anomaly"

Mol Genet Metab. ; 111(4):428-438 ; April 2014
Glioblastoma: a small non-coding RNA (RNU6-1) can be used as a differential diagnostic biomarker, and a 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma
Consult the Pubmed abstracts
To read more about "Glioblastoma"
To read more about "Anaplastic astrocytoma"

Neuro Oncol. ; 16(4):520-7 ; April 2014
PLoS One. ; 9(1):e85200 ; January 2014
Tako-Tsubo cardiomyopathy: a signature of four circulating microRNAs differentiates the disease from acute myocardial infarction
Consult the Pubmed abstract
To read more about "Tako-Tsubo cardiomyopathy"

Eur Heart J. ; 35(15):999-1006 ; April 2014
Creutzfeldt-Jakob disease: the combination of increased T-tau levels and increased T-tau to P-tau ratios may serve as a clinically useful diagnostic test
Consult the Pubmed abstract
To read more about "Creutzfeldt-Jakob disease"

JAMA Neurol. ; 71(4):476-83 ; April 2014

Patient Management and Therapy
A clinical guide to familial Mediterranean fever and other periodic fever diseases
Consult the Pubmed abstract
To read more about "Familial Mediterranean fever"
To read more about "Hereditary periodic fever syndrome"

Nat Rev Rheumatol. ; 10(3):135-47 ; March 2014
IgG4-related diseases: review on the mechanisms and the assessment of the diseases
Consult the Pubmed abstract
To read more about "Immunoglobulin G4-related sclerosing disease"
To read more about "Autoimmune pancreatitis type 1"
To read more about "Mikulicz disease"

Nat Rev Rheumatol. ; 10(3):148-59 ; March 2014
ANCA-associated vasculitis: review on treatments
Consult the Pubmed abstract
To read more about "Anti-neutrophil cytoplasmic antibody-associated vasculitis"
To read more about "Eosinophilic granulomatosis with polyangiitis"
To read more about "Microscopic polyangiitis"
To read more about "Granulomatosis with polyangiitis"

Nat Rev Nephrol. ; 10(1):25-36 ; January 2014
Soft tissue sarcoma: review on standard treatment and novel therapies
Consult the Pubmed abstract
To read more about "Soft tissue sarcoma"

Nat Rev Clin Oncol. ; 11(4):187-202 ; April 2014
Hepatocellular carcinoma : review on clinical frontiers and perspectives
Consult the Pubmed abstract
To read more about "Hepatocellular carcinoma"

Gut ; 63(5):844-55 ; May 2014
XMEN disease: review of the clinical presentation, genetics, mechanisms, diagnostics and therapeutics
Consult the Pubmed abstract
To read more about "X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia"

Blood ; 123(14):2148-52 ; April 2014
Congenital adrenal hyperplasia: review on treatment and health outcomes
Consult the Pubmed abstract
To read more about "Congenital adrenal hyperplasia"

Nat Rev Endocrinol. ; 10(2):115-24 ; February 2014
Glycogen storage disease due to glucose-6-phosphatase deficiency: most complications in liver transplantation seemed related to the procedure
Consult the Pubmed abstract
To read more about "Glycogen storage disease due to glucose-6-phosphatase deficiency"

Orphanet J Rare Dis. ; 9(1):47 ; April 2014
Dravet syndrome: review on the treatment with stiripentol
Consult the abstract
To read more about "Dravet syndrome"

Orphan Drugs: Research and Reviews ; Volume 2014:4 Pages 29 - 38 ; April 2014
Cystic fibrosis: update on biphosphonates for osteoporosis
Consult the Pubmed abstract
To read more about "Cystic fibrosis"

Cochrane Database Syst Rev. ; 3:CD002010 ; March 2014
Atypical hemolytic uremic syndrome: perspectives on cardiovascular complications
Consult the Pubmed abstract
To read more about "Atypical hemolytic uremic syndrome"

Nat Rev Nephrol. ; 10(3):174-80 ; March 2014
Progresses with an orphan ventricular assist device application in children
Consult the Pubmed abstract
Circulation ; 129(14):1530-7 ; April 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:
Prader-Willi syndrome


Orphan Drugs
Regulatory News
12 positive opinions recommending orphan designation at the April 2014 COMP meeting
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted twelve positive opinions issued at the April 2014 COMP meeting for the:

- treatment of biliary tract cancer
- treatment of follicular lymphoma
- treatment of gastro-entero-pancreatic neuroendocrine tumours
- treatment of epidermolysis bullosa
- prevention of scarring in post glaucoma filtration surgery
- treatment of choroideraemia
- treatment of central retinal vein occlusion
- treatment of mucopolysaccharidosis IIIA (Sanfilippo A syndrome)
- treatment of glioma
- treatment of mucormycosis
- treatment of glioma
- treatment of cystic fibrosis

Consult the European Register of Designated Orphan Medicinal Products
Consult the Orphanet list of orphan drugs authorised for marketing in Europe

Pathway for Approval of a Gene Therapy Orphan Product in the US
A commentary published in Molecular Therapy describes the long strides made by the US Food and Drug Administration (FDA) to augment the development and access to gene therapy products as well as recommendations for further improvement in regulation. The author notes that the FDA has yet to approve a gene therapy product but the recent approval of a rare disease treatment based on an adeno-associated virus (AAV) vector in the European Union sets the stage for similar programs to be presented to the FDA in the coming years.

The author describes the current role of, Food and Drug Administration Safety and Innovation Act (FDASIA) to expedite the development and review of innovative medicines that address certain unmet medical needs. Additionally, the new role of agency compels them to meet performance goals that include increasing interaction with drug sponsors during the review process and improving engagement with patients, specifically those with rare diseases.

The author recommends rethinking the traditional approach of staged development that includes developing effective surrogate end points is especially important when there is no alternative treatment and there is a high burden of disease. The author describes the notable role of FDASIA to expand the scope of products that qualify for fast-track status and accelerated approval such as “breakthrough therapy” status to include those intended for the treatment of a serious or life-threatening disease or condition for which there is an unmet medical need as beneficial, although meeting the criteria for accelerated approval is a challenge. The author hopes that once these pathways are mastered by the gene therapy and rare-disease research community many indications may have approved gene therapy product to its name in the US, supporting the rare disease community.
Read the open access article

Political and Scientific News
Rethinking the clinical trials of exon skipping therapy for DMD
Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy patients, but the road to drug approvals is foggy and an article published in Science Magazine makes a case for early-stage derisking and regulatory guidance for innovative strategies.

The focus of this article is the exon skipping therapy which treats a DMD patient systemically with antisense oligonucleotides directed against the dystrophin mRNA transcript restoring the proper reading frame and thus protein production. Although early reports in the mouse model as well the preclinical reports were impressive, the phase III trials of this therapeutic approach carried out by GlaxoSmithKline (GSK) in partnership with Prosensa failed to show significant improvement of the primary outcome measure—the 6-minute walk test. GSK has since terminated its relationship with Prosensa on the exon-skipping program in DMD. An alternative oligonucleotide therapy using morpholinos made by Sarepta showed impressive safety profiles and a wide therapeutic index in two small trials in DMD patients but were not granted accelerated approval by the U.S. Food and Drug Administration (FDA) suggesting, according to the authors, the lack of optimisation and improvement in the clinical approach.

The authors suggest that alternative methods such as alternatives to the 6-minute walk test (such as measures of strength) may have been more acute surrogate measures of potential drug efficacy. Also recommended by the authors was altering dose and chemistry at phase 2 to when greater and more consistent de novo dystrophin production was observed in patient muscle. The authors believe that optimising aspects of the clinical trial design, including younger age of treatment, dose optimization, and improvements in dystrophin protein measurements in patient muscle biopsies could have pave the way to a more compelling accelerated package.
Read the abstract

An article that might help understand the changing patterns of limb function of Duchenne muscular dystrophy (DMD) patients, which in turn might help the assessment of these patients, was published in Journal of Neurology. With increasing life expectancy, upper extremity (UE) function becomes more and more important in boys with DMD. In order to understand these changes the authors distributed a Web-based questionnaire on UE function, covering all domains of the International Classification of Functioning Disability and Health, worldwide. The authors found that UE pain, stiffness, and activity limitations increased with disease stage, despite which only a small number of the respondents used supportive aids. The authors ask the clinicians to pay attention to UE limitations before DMD patients lose their capacity to walk as well as prescribe effective and adequate aids to manage their activity as well as lower restrictions in social participation.
Consult the Pubmed abstract
Could adaptive clinical trials be the answer to developing orphan drugs? Methodologies and challenges explained
A commercial consultancy based in India named the Tata Consultancy Services has produced a report which features the use of adaptive designs to conduct clinical trials. The use of adapting clinical trial methodology has been in discussion in the rare disease field due to the small number of patients and the cost involved in conducting a clinical trial for an Orphan product. Although it is seen as method for making clinical trials cost-effective and time-efficient for conventional drugs, the report highlights some methods which can be used during the development of orphan drugs as well. The report shows how an adaptive clinical trial is conducted in various stages, with access to data at all stages, summarising the different types of adaptive designs, which allows the researcher to stop a trial midway if there is evidence indications of lack of safety or efficacy as well as “sample size (to) be re-estimated, inefficient treatment arms dropped, new arms added and the trial hypothesis changed”, along with the issues and challenges associated with implementing them. The report provides strategies by which at any stage, the data may be analysed and next stages redesigned taking into account all available data (from the trial and even from outside) based on predefined rules. Although challenging, an adaptive clinical trial has several advantages which allows the choosing the most promising option of a drug therapy early as well as correct wrong assumptions, allowing savings in terms of costs and time.
Download the report



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

The Ataxia of Charlevoix-Saguenay Foundation
The Ataxia of Charlevoix-Saguenay Foundation is offering an annual research grants for work aimed at developing treatments for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Such funding is offered regardless of where the research is being conducted and the deadline to apply is May 22, 2014. Further information and the application form can be obtained on the Foundation's website
For further details

Translational consortia for rare diseases research
The funding initiative aims to concentrate research capacities in regional or nationwide research consortia that will develop new knowledge on rare diseases through interdisciplinary cooperation. The research consortia should combine projects on basic research, clinical research and/or health care research into an integrated programme which promises convincing potential for innovation and a short to mid-term effect on improving care for patients. Application Deadline: May 21, 2014
For further details in German

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 may apply for these grants. The award consists of One fellowship of 18000€ for a long exchange and four fellowships of 4500€ for a short exchange. Eligibility criteria for this grant includes exchange with a laboratory or department from another country; involve at least one European laboratory; exchange of benefits to both host and home laboratory.
The deadline for receipt of applications is the 1st October 2014.
To download the application form, click here.
href="http://www.fondation-r-touraine.org/Presentation-and-rules?lang=en" target="_blank"class="Url">For further information.


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 newgroups@institugimagine.org

Call for projects “Preclinical Research in Rare Diseases”
The Rare diseases Foundation launches its first call for projects "Preclinical research in rare diseases: development of translational steps in large animals." The objective of this call for proposals is to support scientific programs pilots at the interface of the proof of concept in vivo obtained in rodents most often, and the development of a clinical application in humans to to improve the well-being of patients.Le Foundation support Rare diseases will allow carriers winners realize their projects in structures known for their expertise, in accordance with European regulations. All the elements to respond to this call for proposals are available you registering / connecting to the professional space , heading Funding Landscape Foundation tab rare diseases.

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
The changing spectrum of IMD: surviving longer and growing old with IMDs
Date: 7-9 May 2014
Venue: London, UK

Aimed at both paediatric and adult metabolic specialist and traineess, this course will discuss issues and address a number of specific controversies in the management of older patients with IMDs.
For further information

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

Intermediate Filaments in Neuromuscular Disorders
Date: 6 July, 2014
Venue: Nice, France

This workshop is a satellite to the XIIIth International Congress on Neuromuscular Diseases (ICNMD2014). The structure of this one-day workshop is organized in 4 sessions dedicated to a particular type of intermediate filament and its associated pathologies: Desmin, Plectin, Synemin and Lamins.
For further information

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 initiated research, ethical considerations, as well as what rare diseases may tell us about common diseases.
Further Information

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


What's on Where?

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

2014 International Collaboration for Clinical Genomics (ICCG)Conference
Date: 11-12 June 2014
Venue: Maryland, US

International Collaboration for Clinical Genomics (ICCG) is creating a universal, clinical-grade database of genomic variation (including structural and sequence variants), available to the public through resources such as NCBI's ClinVar database, and much more. For this conference ICCG encourage the attendance of clinical laboratory personnel (from both cytogenetics and molecular communities), clinicians, genetic counsellors, and others that are interested in setting the standards for clinical-grade databases of genomic variation.
For further information

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

European Reference Networks: Organised by the DG SANCO
Date: 23 June, 2014
Location: Brussels, Belgium

The aim of the conference is to discuss the state of the art on the organisation of highly specialised networks and centres of expertise across the EU and to look into the next steps of the deployment process, in preparation for the forthcoming call for European Reference Networks in 2015.
For further information

Genomic Technologies and Biomaterials for Understanding Disease
Date: 23-24, June, 2014
Location: San Diego, USA

The conference will discuss how advances in biomaterial sciences are being harnessed in the context of genomics and cell based technologies to deepen our understanding of the biology and revolutionize translational medicine. Topics will include advances in sequencing, gene editing and therapy, single cell analysis, stem cell and tissue engineering.
For further information

2014 EWGGD (European Working Group on Gaucher Disease) meeting
Date: 25–28 June, 2014
Location: Haifa Israel

This biannual meeting is organised by the European Working Group on Gaucher Diseases in order to promote the presentation and publication of scientific data and research, and to discuss freely all aspects of Gaucher disease. Physicians, researchers, and patients who are interested in Gaucher disease are welcome to attend the meeting.
For further information

Day To Day With SMA
Date: 28–29 June, 2014
Location: Warwickshire, UK

A day of information, workshops and opportunities to share experiences. Conference sessions are open to anyone aged 16 years + unless otherwise specified. Refreshments and lunch are provided as well as childcare activities for children and young people aged 0 - 15.
For further information

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

Phenotype Day - joint iniative with BioLink and BioOntologies SIG
Date: 12 July, 2014
Venue: Massachusetts, US

Jointly developed by the Bio-Ontologies and BioLINK special interest groups, the Phenotype Day will bring researchers together from different disciplines to share information about phenotype resources and issues as well as experiences with defining, representing, processing and using phenotype data.
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: 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

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

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

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

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, United Kingdom

The topics covered will be of interest to clinicians who deal with rare disorders or have an interest in clinical genetics, IEMs or Paediatrics. It is expected that participants will 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 further information

Third Angelman Syndrome International Meeting (2014)
Date: 18-19 October, 2014
Venue: Paris, France

The French Angelman Syndrome Association (AFSA), organised the Third Angelman Syndrome International Meeting, for researchers and clinicians working on neurosciences, gene therapy, neurological development impairment, more specifically on Angelman syndrome. The meeting is also open to the official representatives of European and national Angelman syndrome organisations (up to 2 persons per organisation).
For further information

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

It will bring together the international scientific community that studies the mechanisms associated with this syndrome to promote exchanges between researchers to advance research in genetics and neuroscience on this rare disease.
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

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

The conference is addressed to Neurologists, Internists, Hematologists and Biotechnologists who deal with diagnostics, 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 characterization of the new aspects of this illness as well as the developments in the clinical environment.
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

Cilia 2014
Date: 18-21 November, 2015
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. It is being organised by 4 European cilia networks: GDR CIL (France), the Ciliopathy Alliance, the Nordic Cilia & Centrosome Network (Scandinavia) and the EU-FP7 SYSCILIA programme.
For Further Information

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

Global partnering opportunities start here World Orphan Drug Congress Europe partnering opportunities are the most efficient and economical way to find a business partner in the orphan and rare disease field. The event plans to bring attendees face-to-face with prequalified buyers who have budget for your solutions. 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

12th European Conference on Rare Diseases: Living with a rare disease
Date: 4–6 July, 2014
Location: Spala, Poland

The objective of the Conference is to introduce the multifaceted nature of rare diseases. The Conference, seminars and training on rare diseases are there to make everyone aware that coordinated actions will allow to improve the quality of life of patients with MPS and rare diseases in Poland and all around the world.
For further information

Commercial events

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


Media, Press & Publications
Book Review: Orphan Drugs - undertstanding the rare disease market and its dynamics
There are limited books that are available describing the current climate surrounding orphan drugs. This book, written by authors Elizabeth Hernberg-Stahl and Miroslav Reljanovic, provides the readers comprehensive information on all aspects of orphan drugs that is useful for a naive as well as an experienced rare disease stakeholder.

The authors provide a historical context to orphan drug policies around the world and how these policies have developed over the course of time with the help of available data. They have described how patient network and advocacy groups have helped in garnering support for the development and advancement of orphan drugs and the policies and regulations that help in bringing them to rare disease patients. Especially of significance in this book is the information on the availability of research funding in EU and USA for rare diseases and how these initiatives are helping further the field of rare disease research. Equally interesting are recommendations for conducting clinical trials of orphan drugs where collaboration and partnership is emphasised. The authors also demonstrate to the readers on how regulatory hurdles can be overcome to obtain marketing authorisation for orphan drugs as well as how these drugs can be accessed in different countries.

The book is an easy read and provides the most up-to-date information from reliable sources and is recommended for rare disease stakeholders trying to grasp the context in which orphan drugs are being developed
Buy the book on Amazon


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: 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

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)
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Photo credit : Serimedis http://www.serimedis.inserm.fr/ (unless otherwise stated)