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ECRD 2014 Berlin: The European Conference on Rare Diseases & Orphan Products attracted over 750 participants from 40 countries

Organised by EURORDIS, in collaboration with the DIA, the 7th European Conference on Rare Diseases and Orphan Products (ECRD 2014) took place 8-10 May in Berlin. ECRD 2014 attracted over 750 stakeholders - patient representatives, health professionals, scientists, industry, policy makers, regulators and payers - from over 40 countries. The conference proposed 36 sessions around six themes: Improving Healthcare Services; Knowledge Generation & Dissemination; Research from Discovery to Patients; State of the Art & Innovative Practices in Orphan Products; Emerging Concepts & Future Policies for Rare Disease Therapies; and Beyond Medical Care.

EU policy and national strategies on shaping rare disease research were widely discussed, as well as concrete experiences at country level. As it is impossible to report briefly on such an important event, only a few topics were picked up to give a flavour of the wide range of topics covered. Tino Münster’s (OrphanAnesthesia) presentation of OrphanAnesthesia described efforts to improve patient safety by publishing recommendations for physicians on rare disease patient anaesthesia. These standardised and peer-reviewed recommendations, based on published research and clinical experience, are available to physicians worldwide.

Kym Boycott (Children Hospital of Eastern Ontario) presented Care for Rare, a pan-Canadian project in support of gene discovery, diagnosis and treatment of rare diseases. Care for Rare aims to improve patient care and establish a favourable eco-system for collaboration, the four essential ingredients of which are: 1) common goals, 2) a community (here, the Canadian College of Medical Geneticists), 3) shared resources and expertise (such as PhenomeCentral) at national and, ideally, international levels, and 4) teamwork, including researchers, clinicians, families and public-private partnerships.

Christine Mummery (Developmental Biology, Leiden University Medical Centre) illustrated how cardiomyocytes (cardiac muscle cells) derived from induced pluripotent stem (iPS) cells of patients with inherited arrhythmias provide a better understanding of the disease and an alternative to animal models in clinical research. These iPSCs disease models show notable potential for drug research and development, drug toxicology and safety pharmacology.

Luca Pani (Italian Medicines Agency), Pauline Evers and Pat Furlong (European genetic alliances network / Dutch Federation of Cancer Patient Organisations), Mark Rothera (PTC Therapeutics) and Yann Le Cam (EURORDIS) discussed the European Medicines Agency’s adaptive licensing pilot project. Adaptive licensing aims to improve timely access to new treatments through post-marketing authorisation clinical safety and efficacy studies (PASSs/PAESs). The rationale for setting clinical endpoints and therapeutic outcomes for rare disease treatments raised many issues.

Thomas Heynisch (European Commission) led discussions on the Mechanism of Coordinated Access (MoCA) to orphan medicinal products (OMPs). Four stakeholder representatives from the MoCA working group, Wills Hughes-Wilson (Sobi), Yann Le Cam, Ri De Ridder (RIZIV-INAMI) and Luca Pani, further discussed optimising patient access to OMPs, tackling issues such as pricing and reimbursement at national level, and managed entry agreements. The group presented the Transparent Value Framework as a means for stakeholders to question the value of individual OMPs, discuss in-country pricing and reimbursement, and consider managed entry agreements. The reports of the MoCA working group are available online.

As increasing numbers of rare diseases are discovered, so are patients who suffer from them. European agencies and the industry are responding to unmet needs and scientific advancement through research and development funding prioritisation. ECRD 2014 Berlin highlighted the importance of collaboration and coordination, from research to patient care and reimbursement. Dialogue remains essential at all stages and with all stakeholders to enhance value in rare disease projects.

EURORDIS will publish a full report later on this year. In the meantime, Presentations and posters are available online.

The next ECRD will take place in 2016 in Edinburgh.

Photos courtesy of EURORDIS


EU Policy News

Second meeting of the Expert Group on Rare Diseases
The second meeting of the Commission Expert Group on rare diseases will be held in Luxembourg on 3-4 July 2014. The Expert Group replaces the European Union Committee of Experts on Rare Diseases (EUCERD) and brings together Member State representatives and a wide range of stakeholders to aid the European Commission in their implementation of Community measures in the field of rare diseases. A number of important topics will be tackled by the Expert Group at the meeting, including the codification of rare diseases, European Reference Networks for rare diseases in the framework of the Cross-Border Healthcare Directive and the Commission report on the implementation of the Commission Communication on Rare Diseases: Europe's Challenge and the Council Recommendation of 8 June 2009 on an action in the field of rare diseases.


Out with the old, in with the new - European initiatives to address rare diseases
This review by two EC scientific officers, published in Public Health Genomics, revisits a number of European initiatives implemented over the past years to address the need to harmonise rare disease research, classification, diagnosis and treatment. In efforts to coordinate collaboration on rare diseases across Europe, the EU’s Task Force on Rare Diseases (2004 to 2009) was the first stakeholder forum at European level to encourage cooperation in the field of rare diseases. The Task Force was followed by the European Union Committee of Experts on Rare Diseases (EUCERD) (2010 to 2013) and the newly formed European Commission Expert Group on Rare Diseases (2014), established via Commission Decision 2013/C 219/04 of 30 July 2013, whose mandate is to increase transnational coordination and expertise on rare diseases. The International Rare Diseases Research Consortium (IRDiRC) was launched in 2011 in order to achieve wider international research cooperation on rare diseases.

The article recalls the outcomes of the European Organisation for Rare Diseases (EURORDIS) survey of diagnostic delays for 8 rare diseases, via the Rare Disease Patient Solidarity (RAPSODY) project. Results highlighted the urgent need to step up diagnostic efficiency. The US National Commission on Orphan Diseases reported similarly unsatisfactory results. In view of this relatively poor understanding of rare diseases, diseases must be adequately coded throughout health systems globally in order to be effectively diagnosed and recognised by national healthcare services. The EU is assisting the WHO on revising the International Classification of Diseases (ICD), notably in efforts to improve codification and classification of rare diseases worldwide, through a Joint Action. Orphanet’s in-house classification is contributing to the ICD revisions, expected for May 2017. The article also highlights the important role of patient registries in conducting clinical research on rare diseases. The European Commission proposes a common platform, the EU Rare Disease Registration Platform (EURDP), to represent national registries, and serve both scientific and patient communities.

As the EU continues its efforts to meet the needs of rare disease patients, projects continue to be developed to improve the quality of research and information on rare diseases in order to accelerate diagnosis and patient care.


National & International Policy Developments

Audit of NHS’ Genetic Test Evaluation
The recently published audit by the UK Genetic Testing Network (UKGTN) reports on the activity and costs associated with genetic tests performed between 1st April 2012 and 31st March 2013, based on tests introduced into the UK’s National Health Service (NHS) between 2007 and 2010. The UKGTN evaluates new genetic tests for rare disorders that laboratories wish to offer NHS patients. Laboratories submit a gene dossier to the UKGTN Genetic Test Evaluation Working Group. Following authorisation by the UKGTN Clinical and Scientific Advisory Group and NHS genetic services, approved tests are listed online and added to the NHS Directory of Genetic Disorders/Genes for Diagnostic Testing. Since 2003, when the gene dossier process was piloted, the UKGTN has evaluated 444 gene dossiers and recommended 353.

Twenty two laboratories out of twenty four provided data covering the 2012-2013 one year period. Overall, 5,253 (92%) index cases were reported by selected and other laboratories out of 5,708 predicted index cases, and 1,522 (65%) familial cases were reported by selected and additional laboratories out of 2,341 predicted familial cases. Laboratories therefore predicted index case activity more accurately than family case activity. The report suggests that size variation and disease risk assessment within families may influence the activity outcome. Certain laboratories, such as Birmingham RGC, Dundee and Leeds reported results vastly superior to predicted data. On the other hand, Oxford, Salisbury, Sheffield and Cambridge significantly overestimated results for either index data or familial cases. The audit recommends that such cases be investigated individually.

Regarding costs, a range of values was provided to commissioners in the gene dossiers, depending on the type of test. Estimated minimum and maximum cost scenarios were calculated, based on minimum numbers of tests at minimum cost (e.g. familial testing) on the one hand, and maximum numbers of expensive tests (e.g. coding regions or whole gene testing) on the other hand. Cost estimates for tests approved from 2007 to 2010 ranged from £3,055,366 (lowest), £3,282,560 (mid) to £3,509,698 (highest). The laboratories reported actual costs for tests far below estimated gene dossier mid- and low cost estimates. While original cost estimates for 2012-2013, based on gene dossier prices, established total cost at £3,232,604, actual costs applied reached only £2,861,291 for all laboratories, including additional providers. Out of the 24 audited laboratories, 15 reported below or equivalent to estimated costs, 5 reported slightly above estimates, while 4 did not provide results. The audit confirms that estimates applied to the UKGTN genetic test evaluation process are sound and recommends continuous monitoring.

NIH’s arms continue to grow for the benefit of the RD community
An article published in Public Health Genomics sums up the US National Institutes of Health's (NIH) initiatives to increase and improve research on rare diseases. Besides information sources such as Clinical-Trials.gov, PubMed and the Genetic Testing Registry, a number of information sources were launched in the past ten years for rare disease research. They include the Rare Diseases Clinical Research Network (RDCRN), the Genetic and Rare Diseases Information Center (GARD) and the Undiagnosed Diseases Program, the Therapeutics for Rare and Neglected Diseases Program (TRND) among others. Further information databases have been developed to assist rare disease communities. They include the Research Portfolio Online Reporting Tools, which provides reports on NIH research activities and training, and the Research, Condition, and Disease Categorization (RCDC) for access to research projects on rare diseases and orphan products. The RDCD provides information on over 230 disease categories, conditions and research areas, as well as funding data. In 2012, the NIH awarded USD 3.6 billion to 9,400 rare disease research projects, representing 14.2% of NIH’s USD 25.5 billion budget for grants, contracts, training and research facilities.

The NIH’s latest development, The National Center for Advancing Translational Sciences (NCATS), was launched in December 2011 to accelerate translational research through to patient solutions. NCATS promotes collaboration among various stakeholders, including government agencies, academics, industry and patient advocacy groups. In June 2013, NIH invested USD 12.7 million into nine projects through the NCATS programme. The earlier NIH Common Fund was introduced in 2006 to provide short term investment, and the support of two or more NIH programmes, in order to address high-impact emerging research and translational opportunities. NIH’s Bench-to-Bedside Program, launched in 1999 to foster collaboration between basic scientists and clinical investigators, was extended to non-NIH Intramural Research Program institutions. Since 2006, 74 extramural collaborators have been involved in Bench-to-Bedside projects. In 2008, the NIH launched the Intramural Research Program on undiagnosed diseases, or Undiagnosed Diseases Program. Based on the success of this programme, the NIH is setting up the Common Fund’s Undiagnosed Diseases Network (UDN), to promote a cross-disciplinary approach to rare and new disease diagnosis.

The Office of Rare Diseases Research (ORDR) has launched a two year pilot Global Rare Diseases Patient Registry and Data Repository (GRDR). GRDR aims to establish a global repository of de-identified patient information and clinical data in order to facilitate biomedical studies on rare disease. The ORDR also set up the Rare Disease Human Biospecimen database (RD-HuB) providing information on human biospecimens collected globally. Aware of the need to increase public-private partnerships between stakeholders, the NIH continues its efforts to initiate new and update old programmes to stimulate rare disease research, diagnostic competence and orphan product development. In the US, where 6% of the population suffers from a rare disease and where research resources are increasingly limited, the NIH has highlighted the need for “a more systematic and coordinated approach to rare diseases research and orphan products development”.
Consult the PubMed abstract

Other European news
CIBERER launches a tool to filter exome variants found in the Spanish population
The Centre for Biomedical Network Research on Rare Diseases (CIBERER), in collaboration with the Instituto Nacional de Bioinformática (INB), has launched the CIBERER Exome Server, a public, free online tool designed to improve the selection of potentially pathogenic genetic variants found in Spanish individuals. As local variations could be significant, this server will contribute to other international available exome servers. Any researcher using CIBERER Exome Server will be able to obtain information about all variants detected in the Spanish population. CIBERER aims to set up a repository of variant data contributed by all investigators (academic, clinical or industrial) having sequenced exomes from Spanish individuals.

Guidance Documents and Recommendations
Multiple myeloma: updates on diagnosis and management guidelines
An updated version of the guidelines on diagnosis and management of multiple myeloma, originally published in 2001, is now available on the British Committee for Standards in Haematology website. A letter, published in the British Journal of Haematology, highlights the three main addendums to the guideline.
To read more about "Multiple myeloma"

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

Bioinformatics, Registries and Data Management

European PedNet Haemophilia Registry
Haemophilia affects one in 5,000 male births and is now one of the most treatable rare diseases. Most children in developed countries receive primary prophylactic treatment. Prophylaxis infusions and cost are, however, burdensome. Treatment is further complicated by the development of allo-antibodies, or inhibitors, against factor VIII or IX therapy. In an effort to improve treatment, this article in Haemophilia studies the design and implementation of the PedNet Haemophilia Registry. This collaborative registry, set up in 2004 by the European PEDiatric NETwork for haemophilia management, involves 30 Haemophilia Treatment centres (HTCs) from 16 countries.

The PedNet registry monitors patients until their 20th birthday and focuses on neonatal complications, development of inhibitors to coagulating factors, bleeding phenotypes, treatment regimens and side effects, and venous devices for prophylaxis administration. By May 2013, the registry monitored 1,094 patients with severe (64%), moderate (13%) and mild (23%) haemophilia A and B. Due to a very high inclusion rate (93-99%) of eligible patients, the registry was able to collect data on most known risk factors associated with inhibitor development, as well as safety and efficacy results of new and old treatments. Demonstrated by the success of PedNet, the authors suggest that similar collaborative observational cohort studies could be applied to investigate and improve treatment for other rare diseases.

Screening and Testing

The freckly diagnostic criteria for Neurofibromatosis 1
Neurocutaneous disorder, Neurofibromatosis 1 (NF1), affects around one in 3,500 newborns. Diagnosis is based on current criteria recommended by the National Institute of Health Consensus Conference. The disease affects the nervous system, skin, eyes and bones. While precise molecular analyses now confirm diagnosis in 95% of patients by the age of eight years, detection and patient care remain challenging due to symptom variations, unpredictable disease evolution and lack of awareness of disease characteristics. This review in the European Journal of Internal Medicine highlights the insufficient current clinical criteria to conduct efficient diagnosis and stresses the need for updated guidelines.

NF1 is transmitted either genetically or, in 50% of cases, occurs through spontaneous mutations. It is therefore impossible to base the disorder on genetic inheritance alone. As a number of spontaneous mutations in NF1 patients are unknown, patients presenting with symptoms are often negative to current genetic tests. On the other hand, patients carrying a mutation on the NF1 gene might not show signs of the disease. Nevertheless, the authors highlight the need to include genetic analysis into the diagnosis.

Clinical signs of NF1 include café-au-lait macules, freckling, Lisch nodules and neurofibromas. The authors believe that all cutaneous signs are essential criteria in early diagnosis. Many extra-cutaneous signs, including Lisch nodules, optic pathway gliomas and bone anomalies are not systematically detected in early childhood. Though difficult in young patients, ocular examination could facilitate the detection of optic pathway glioma. The authors further suggest that ophthalmological signs of choroidal nodules could contribute to diagnosis in young children. Detection of NF1 is made all the more complicated by less frequent signs such as focal osteopathy, precocious puberty, short stature, insufficient bone mineralisation, aneurysms, stenoses, arterial and cardiovascular malformations, seizures, headaches, and even attention deficit hyperactivity disorders. All these signs, therefore, need to be taken into consideration when assessing children with suspected NF1.

As therapeutic management of NF1 addresses NF1-related complications essentially, no treatment exists for NF1-related tumours. Again, the authors highlight the need for early diagnosis in order to improve patient follow-up from childhood to adulthood and address symptom-related complications as early as possible. The authors recommend that a new Consensus Conference of NF1-experienced clinicians and molecular biologists should draw up an updated list of age-related diagnostic criteria.

Good variants, bad variants - The challenges of distinguishing them
As high throughput sequencing accelerates, so does the discovery of vast numbers of genetic variants. Though many variants are strongly associated with rare or common genetic disorders, non-pathogenic variants are sometimes misinterpreted as disease-causing. In one study, over a quarter of severe disease causing mutations sequenced in a set of 104 individuals were reported to be non-pathogenic. This illustrates how false-positives in patients could result in unnecessary treatment or misleading reproductive advice. The scientific community might also allocate unnecessary resources to research. This Nature article offers guidelines to conduct human genome sequencing in order to distinguish disease causing variants from non-pathogenic or functional variants.

The authors base their recommendations on five key areas: study design, gene-level implication, variant-level implication, publication and databases, and implications for clinical diagnosis. Researchers investigating pathogenic variants should consider techniques best adapted to the likely genetic disorders. For instance, exome sequencing is frequently used to investigate presumed monogenic disorders. Concerning gene involvement, investigators must demonstrate the impact of all variations in a gene implicated in a disorder. Additionally, in order to avoid misinterpreting the role of variations in gene disruption, investigators must systematically compare their findings with non-disease-related genes. All rare disorders may not, however, offer control measures, due to the scarcity of evidence. In such cases, comprehensive gene, informatic and experimental cross-analyses are recommended. As many rare non-pathogenic variants appear in most human genomes, particular caution must therefore be taken when establishing a causal role of variants in disease expression.

In order to increase the quality and quantity of evidence on variant pathogenicity, the authors recommend building open-source registries to centralise and update data on sequence variants and their consequences on gene expression. The US National Center for Biotechnology Information (NCBI)’s ClinVar database will link information with other initiatives such as LOVD (Leiden Open (source) Variation Database), OMIM (Online Mendelian Inheritance in Man) and DECIPHER in an effort to coordinate data repositories globally. The authors emphasise that data sharing will accelerate evidence gathering and analysis of variant implication in gene disorders. Open databases will further contribute to clinical diagnosis, where misdiagnosis could have severe consequences on patient care. Eventually, the richer the shared information is, the more robust it will become and the easier it will be to establish levels of certainty in evidence for variant implication in disorders.


Ethical, Legal & Social Issues

Tweet tweet – Patient, are you there for clinical research?
“In a world in which excessive sharing of information is becoming increasingly normalised, maintenance of patient privacy has never been more important”, concludes this Lancet editorial regarding the advantages and pitfalls of resorting to social media and crowdsourcing to recruit patients in clinical research. The more people ‘Google’, ‘Facebook’, ‘Tweet’ and ‘blog’ about rare diseases, the more they become aware of what is going on in the rare disease community. Besides enabling patients to become more informed, the author suggests that social media also allow individuals to play an increasingly active part in their disease management, from diagnosis to clinical trial enrolment. By engaging in online communities, patients might also become more willing to take part in clinical trials. The article confirms that researchers do recruit patients directly through online patient support groups. In the US for instance, patients are able to sign up for clinical trials on the CureLauncher website.

To avoid bias however, patient anonymity is essential in clinical trials. But as patients continue to blog and exchange information online whilst enrolled in a clinical trial, they might inadvertently reveal their identity and clinical trial regimen to researchers, thus discrediting the purpose of blind studies. The author raises further questions concerning the protection of patient anonymity and patient data ownership in social networks. Typically, as patients become more informed and engaged, so do they face greater risks of overexposure and under-protection from misleading information or information they cannot interpret adequately. Rather than undermine social media however, the author recommends that clinicians take them into consideration when designing clinical trials.


New Syndromes

New syndrome of epileptic encephalopathy and cortical blindness caused by mutations of DOCK7
The authors described three girls from two non-consanguineous families affected by a clinical entity characterized by dysmorphic features, early-onset intractable epilepsy, intellectual disability, and cortical blindness. The loss of DOCK7 function causes this syndromic form of epileptic encephalopathy.
Consult the Pubmed abstract

Am J Hum Genet. ; [Epub ahead of print] ; May 2014
An autosomal-dominant form of metabolic syndrome associated with DYRK1B mutations in three families
The authors identified three large families with coinheritance of early-onset coronary artery disease, central obesity, hypertension, and diabetes. A founder mutation was identified in DYRK1B.
Consult the Pubmed abstract

N Engl J Med. ; 370(20):1909-19 ; May 2014
White matter disease, intellectual disability, and microcephaly suspected to be caused by a novel homozygous DEAF1 variant
The authors described two children from a consanguineous family with intellectual disability, microcephaly, and hypotonia. The brain MRI of both patients showed bilateral and symmetrical white matter abnormalities. A homozygous mutation in DEAF1, inherited from asymptomatic parents, was found in both patients.
Consult the Pubmed abstract

Am J Med Genet A. ; 164(6):1565-70 ; June 2014

New Genes

Childhood-onset recessive Mendelian form of steroid-sensitive and steroid-resistant nephrotic syndromes due to EMP2 mutations
Consult the Pubmed abstract
To read more about "Idiopathic steroid-sensitive nephrotic syndrome"
To read more about "Familial idiopathic steroid-resistant nephrotic syndrome"
To read more about "Familial idiopathic steroid-resistant nephrotic syndrome with minimal changes"

Am J Hum Genet. ; [Epub ahead of print] ; May 2014
Neu-Laxova syndrome is an inborn error of serine metabolism, due to mutations in PHGDH
Consult the Pubmed abstract
To read more about "Neu-Laxova syndrome"

Am J Hum Genet. ; [Epub ahead of print] ; June 2014
Primary ciliary dyskinesia with reduced generation of multiple motile cilia is associated with mutations in CCNO
Consult the Pubmed abstracts
To read more about "Primary ciliary dyskinesia"

Nat Genet. ; [Epub ahead of print] ; April 2014
Eur J Hum Genet. ; [Epub ahead of print] ; May 2014
Childhood-onset dilated cardiomyopathy linked to RAF1 mutations
Consult the Pubmed abstract
To read more about "Dilated cardiomyopathy"
To read more about "Familial isolated dilated cardiomyopathy"

Nat Genet. ; [Epub ahead of print] ; April 2014
Autosomal-recessive severe congenital neutropenia associated with a frameshift mutation in CXCR2
Consult the Pubmed abstract
To read more about "Severe congenital neutropenia"

Nat Genet. ; [Epub ahead of print] ; April 2014
Familial amyotrophic lateral sclerosis linked to mutations in MATR3
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis"

Nat Neurosci. ; 17(5):664-6 ; May 2014
Autosomal-dominant retinitis pigmentosa due to PRPF4 mutations
Consult the Pubmed abstract
To read more about "Retinitis pigmentosa"

Hum Mol Genet. ; 23(11):2926-39 ; June 2014
Autosomal-dominant juvenile cataract associated with missense mutation in UNC45B in a family
Consult the Pubmed abstract
Eur J Hum Genet. ; [Epub ahead of print] ; February 2014
Autosomal-dominant split-hand/foot malformation caused by a heterozygous DLX5 mutation in a Chinese family
Consult the Pubmed abstract
To read more about "Split hand-split foot malformation"

Eur J Hum Genet. ; [Epub ahead of print] ; February 2014
Mild Joubert syndrome due to mutations in B9D1 or MKS1 in four patients
Consult the abstract
To read more about "Joubert syndrome"

Orphanet Journal of Rare Diseases ; 9:72 ; 2014
Autosomal-recessive palmoplantar keratoderma and woolly hair, without cardiomyopathy, caused by a mutation in KANK2, in two large consanguineous families
Consult the Pubmed abstract
J Med Genet. ; 51(6):388-94 ; June 2014
Diffuse type gastric carcinoma associated with recurrent driver mutations of RHOA
Consult the Pubmed abstracts
Nat Genet. ; [Epub ahead of print] ; May 2014
Nat Genet. ; [Epub ahead of print] ; May 2014

Research in Action

Clinical Research
Kawasaki disease: mixed results with the addition of infliximab to primary treatment
Consult the Pubmed abstract
To read more about "Kawasaki disease"

Lancet ; 383(9930):1731-8 ; May 2014
Pediatric idiopathic and/or familial pulmonary arterial hypertension: favorable survival for children with sildenafil although higher mortality was observed with higher doses
Consult the Pubmed abstract
To read more about "Idiopathic and/or familial pulmonary arterial hypertension"

Circulation ; 129(19):1914-23 ; May 2014
Biliary atresia: high-dose steroid therapy following hepato-porto-enterostomy did not improve bile drainage
Consult the Pubmed abstract
To read more about "Biliary atresia"

JAMA ; 311(17):1750-9 ; May 2014
Relapsed T-cell lymphoma: mogamulizumab and brentuximab vedotin exhibited antitumor activity with an acceptable toxicity profile
Consult the Pubmed abstracts
J Clin Oncol. ; 32(11):1157-63 ; April 2014
Blood ; 123(20):3095-100 ; May 2014
Idiopathic intracranial hypertension: the use of acetazolamide with a low-sodium weight-reduction diet compared with diet alone did not significantly improve mild visual loss
Consult the Pubmed abstract
To read more about "Idiopathic intracranial hypertension"

JAMA ; 311(16):1641-51 ; April 2014
Cerebral arteriovenous malformation: the use of conservative management compared with intervention was associated with better clinical outcomes for up to 12 years
Consult the Pubmed abstract
To read more about "Cerebral arteriovenous malformation"

JAMA ; 311(16):1661-9 ; April 2014
Steroid-dependent or frequently relapsing idiopathic nephrotic syndrome: rituximab might prevent recurrences and reduce the need for immunosuppression
Consult the Pubmed abstract
To read more about "Idiopathic steroid-sensitive nephrotic syndrome"

J Am Soc Nephrol. ; 25(4):850-63 ; April 2014
Cushing disease: ketoconazole is an effective drug that should be used under close liver enzyme monitoring
Consult the Pubmed abstract
To read more about "Cushing disease"

J Clin Endocrinol Metab. ; 99(5):1623-30 ; May 2014
Aggressive and indolent adrenocortical carcinomas correspond to two distinct molecular entities driven by different oncogenic alterations
Consult the Pubmed abstract
To read more about "Adrenocortical carcinoma"

Nat Genet. ; [Epub ahead of print] ; April 2014
A recurrent MYOD1 mutation defines a clinically aggressive subset of embryonal rhabdomyosarcomas eligible for high-risk protocols and the development of targeted therapeutics
Consult the Pubmed abstract
To read more about "Embryonal rhabdomyosarcoma"

Nat Genet. ; [Epub ahead of print] ; May 2014
Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma
Consult the Pubmed abstract
To read more about "Neuroblastoma"

J Clin Oncol. ; 32(10):1074-83 ; April 2014
Stem Cells

Glial tumor: treatment using TRAIL-secreting human mesenchymal stem cells combined with temozolomide had greater therapeutic efficacy than single-agent treatments
Consult the Pubmed abstract
To read more about "Glial tumor"

Stem Cells Transl Med. ; 3(2):172-82 ; February 2014
Retinitis pigmentosa: transplantation of photoreceptors derived from human Muller glia restores rod function in the P23H rat
Consult the Pubmed abstract
To read more about "Retinitis pigmentosa"

Stem Cells Transl Med. ; 3(3):323-33 ; March 2014
Huntington disease: intrastriatal transplantation of adenovirus-generated induced pluripotent stem cells may provide a potential venue for therapeutic treatment
Consult the Pubmed abstract
To read more about "Huntington disease"

Stem Cells Transl Med. ; 3(5):620-31 ; May 2014
Gene Therapy
Huntington disease: viral delivery of Kir4.1 channels to striatal astrocytes prolonged survival and attenuated some motor phenotypes in R6/2 mice
Consult the Pubmed abstract
To read more about "Huntington disease"

Nat Neurosci. ; 17(5):694-703 ; May 2014
Therapeutic Approaches

Huntington disease: selisistat, a potent and selective Sirtuin 1 inhibitor, alleviates pathology in Drosophila, mammalian cell and mouse models
Consult the Pubmed abstract
To read more about "Huntington disease"

Hum Mol Genet. ; 23(11):2995-3007 ; June 2014
Review on sound strategies for hearing restoration
Consult the Pubmed abstract
Science ; 344(6184):1241062 ; May 2014
Diagnostic Approaches

Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency
Consult the Pubmed abstract
To read more about "Primary immunodeficiency"

Front Immunol. ; 5:162 ; April 2014
Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘Care for CMMRD’
Consult the Pubmed abstract
To read more about "Constitutional mismatch repair deficiency syndrome"

J Med Genet. ; 51(6):355-365 ; June 2014
Amyotrophic lateral sclerosis: fluorodeoxyglucose-positron-emission tomography is a useful early diagnostic and prognostic marker
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis"

JAMA Neurol. ; 71(5):553-61 ; May 2014
Primary progressive aphasia: phonologic errors seem to be highly predictive of high amyloid burden and can provide a specific marker for logopenic variant
Consult the Pubmed abstract
To read more about "Logopenic progressive aphasia"

Neurology ; 82(18):1620-7 ; May 2014

Patient Management and Therapy
Amyotrophic lateral sclerosis: venous thromboembolism is common in patients with leg weakness and should thus be explored in high-risk patients
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis"

Neurology ; 82(19):1674-7 ; May 2014
X-linked adrenoleukodystrophy: small nerve fiber dysfunction is frequent
Consult the Pubmed abstract
To read more about "X-linked adrenoleukodystrophy"

Neurology ; 82(19):1678-83 ; May 2014
Adult-onset granulosa cell tumors of the ovary: review on effectiveness of different treatment modalities
Consult the Pubmed abstract
To read more about "Granulosa cell malignant tumor"

Cochrane Database Syst Rev. ; 4:CD006912 ; April 2014
Hemophilia A and B: review on immune tolerance induction for treating factor inhibitory antibodies
Consult the Pubmed abstract
To read more about "Hemophilia A"
To read more about "Hemophilia B"

Cochrane Database Syst Rev. ; 4:CD010561 ; April 2014
Cystic fibrosis: no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition
Consult the Pubmed abstract
To read more about "Cystic fibrosis"

Cochrane Database Syst Rev. ; 4:CD005087 ; April 2014
Cystic fibrosis: antibiotic treatment did not show significant efficacy in two reviews
Consult the Pubmed abstracts
To read more about "Cystic fibrosis"

Cochrane Database Syst Rev. ; 4:CD009249 ; April 2014
Cochrane Database Syst Rev. ; 4:CD002007 ; April 2014
Conotruncal heart malformations: recurrence risk in relatives of probands varies by lesion and on degree of relationship
Consult the Pubmed abstract
To read more about "Conotruncal heart malformations"

Am J Med Genet A. ; 164(6):1490-5 ; June 2014
Referral to specialized adult congenital heart disease care is associated with a significant mortality reduction
Consult the Pubmed abstract
Circulation ; 129(18):1804-12 ; May 2014
Osteogenesis imperfecta: review on clinical diagnosis, nomenclature and severity assessment
Consult the Pubmed abstract
To read more about "Osteogenesis imperfecta"

Am J Med Genet A. ; 164(6):1470-81 ; June 2014
Epilepsy: genetic testing and gene therapy
Consult the Pubmed abstracts
Nat Rev Neurol. ; 10(5):283-92 ; May 2014
Nat Rev Neurol. ; 10(5):293-9 ; May 2014
Nat Rev Neurol. ; 10(5):300-4 ; May 2014
Li-Fraumeni syndrome: review on cancer risk assessment and clinical management
Consult the Pubmed abstract
To read more about "Li-Fraumeni syndrome"

Nat Rev Clin Oncol. ; 11(5):260-71 ; May 2014
Multicentric Castleman disease: review on biology, pathogenesis, and therapy
Consult the Pubmed abstract
To read more about "Multicentric Castleman disease"

Blood ; 123(19):2924-33 ; May 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:
15q13.3 microdeletion syndrome


Orphan Drugs

Decrypting orphan drug pricing and reimbursement
As studies continue to pore over the rationale behind orphan drug pricing, the significant variability in treatment costs - from a few thousand to several hundred thousand Euros per patient per year - continues to be a puzzling and sensitive issue for payers. This review of the literature and statistical analysis attempt to decrypt orphan drug pricing and reimbursement mechanisms. Past studies have suggested inverse correlation between cost and prevalence: the rarer the disease, the higher the cost.

The investigators of a study, published in Orphanet Journal of Rare Diseases, incorporated a number of additional variables into their analysis, namely drug-, disease- and country-specific data. Based on the 65 authorised orphan drugs, listed by the European Medicines Agency in April 2013, the study compares and contrasts factors influencing orphan drug costs in six European countries. The authors observe that criteria such as availability in the United States, multiple orphan indications, chronic treatment, demonstrated improved quality of life, survival and ultra rare indications appear to push orphan drug prices up. Alternatively, substitute, repurposed and orally administered orphan drugs, or orphan drugs marketed by medium- to large-size pharmaceutical companies appear to cost less.

While this study highlights the relation between average annual orphan drug treatment cost and seven variables, each country’s pricing and reimbursement system appears to have little or no significant influence on orphan drug pricing. The authors advise, however, against concluding that prices are uniform across Europe, since the study based its analysis on countries with comparable orphan drug reimbursement capacities. Additionally, final prices are established after closed-door negotiations between payers and distributers, further contributing to the complexity of pricing mechanisms. In this grey area of drug pricing, the authors highlight past recommendations on the need for greater transparency, through a proposed Transparent Value Framework (TVF), concerning price determination. The TVF proposal does emphasise, however, the need for further study if it is to be applied in the context of value-based pricing (VBP), as illustrated by the UK’s NICE attempt to introduce VBP.

A tough exam for orphan drugs in some countries
With the high cost of orphan drugs comes high stringency concerning reimbursement by government health insurers. This article, published in the Journal of Market Access and Health Policy, examines orphan drug coverage policies in the United States, England, Wales and the Netherlands. Whilst in the UK and the Netherlands, authorised orphan drugs are generally covered entirely by national health services, the authors observe a growth in out-of-pocket payment for orphan drug treatments in the US, through increasing co-payments - or co-insurance - per prescription. In other words, patients have to dig deeper into their pockets to top up treatment payment, up to 28% of orphan drug prices, representing tens of thousands of dollars per year for some patients.

In an attempt to curb costs to payers, health authorities in the US, the UK and the Netherlands apply different orphan drug coverage recommendations. Findings from the study suggest that these recommendations invariably result in higher reimbursement restrictions for orphan drugs than for non-orphan drugs. Since, however, orphan drug treatment applies to only a small proportion of the population, the authors maintain that the cost of treating these patients would anyway remain low. The conclusions of the study further question the rationale behind preferential orphan drug coverage based on per unit cost – as opposed to a combination of clinical effectiveness, cost-effectiveness and budget impact analyses.

The authors maintain that orphan drugs should be subject to the same evaluation criteria as non-orphan drugs are. In a further effort to improve rare disease patient access to treatment, as well as orphan drug efficacy and safety, the study also suggests that payers could provide patients temporary and adjustable access to orphan products, whilst these undergo ongoing clinical evaluation.

NICE but misbehaving – Challenging orphan drug prices
For the first time, the UK’s National Institute for Health and Clinical Excellence (NICE) has questioned orphan product manufacturer, Alexion Pharmaceuticals, on the development and manufacturing costs of orphan drug Solaris® (eculizumab), indicated to reduce the degradation of red blood cells in patients suffering from paroxysmal nocturnal haemoglobinuria (PNH). Following its health technology assessment (HTA) of Solaris®, NICE granted the drug a favourable assessment, but has requested further details concerning the high price of the treatment, £340,200 (USD 568,583) per patient per year.

In a recent editorial in Nature, the author strongly criticises NICE’s action, stating that the institute is wrong to base orphan drug value on research and development costs only. The article argues that multiple criteria must be taken into consideration, not least of all the costs of R&D on unsuccessful, yet essential, projects the laboratory needs to account for. The author expresses further concern that NICE’s stance could throw into turmoil the entire basis of orphan drug assessment, with severe repercussions on orphan product research and development.

Regulatory News
Putting labels on off-label indications of medical products
Off-label use of drugs could benefit certain patients - including rare disease patients -, physicians and pharmaceutical companies. This review of the literature, published in the Journal of Pharmacology and Pharmacotherapeutics, highlights the benefits and potential, but also the risks, of off-label drug prescriptions. Some patients and physicians might benefit from receiving and prescribing, respectively, a treatment that has not be granted regulatory approval for a particular indication, but is documented as demonstrating efficacy and safety in clinical research for that indication. One such example is cancer drug Avastin®, authorised for orphan and non-orphan disorders and recognised, but not regulatory-authorised, to treat age-related wet macular degeneration as an alternative to Lucentis®, Genetech’s costly authorised drug.

Certain drugs, used off-label, are prescribed to treat rare disease patients for whom no approved treatment exists. As the potential of off-label use of a drug becomes increasingly recognised by experts and health authorities, off-label indications for that drug stand a better chance to become regulatory-approved. Besides offering a treatment for certain unmet medical needs, pharmaceutical companies also welcome the opportunity of drug repurposing and the potential to broaden their market.

Concerned, however, about the efficacy and safety of off-label use, the authors highlight the need for closer guidance from regulatory authorities. Though most countries have not implemented clear regulation for off-label prescriptions, some countries, such as the US and France, have introduced legislations and recommendations in an effort to increase risk-benefit analyses and provide safer and more educated off-label use of drugs. The recently passed French decree on Temporary Recommendations for Use aims to strengthen the safety of medical products used off-label and facilitate the development of new indications (read more on New drug regulations in France). In the US, the FDA issued a recently updated Guidance for Industry regarding the distribution of scientific publications on unauthorised indications and recommended practices for off-label use of medical products. Hence, the authors suggest that educated use of drugs for off-label indications should be encouraged as long as it remains beneficial and safe for patients.

More siblings for orphan drugs
“Orphan drugs are overtaking the [FDA] agency”, says a former director of the Office of Orphan Products Development (OOPD). According to an article in Nature, over a third of FDA-approved drugs in 2013 were orphans. This trend concerns some who denounce the escalation of orphan drug designations for common diseases. One example is the treatment for sickle-cell anaemia. Though rare in the US, this disease is rife in Africa. Such a large patient base, outside the US, represents a potentially - and opportune - vast market for some pharmaceutical companies.

Critics complain that drug developers increasingly apply for orphan designations in order to take advantage of potential market exclusivity, user fee waivers and tax credits for clinical trial costs - incentives originally introduced to boost a sluggish orphan drug market. Some critics go as far as suggesting companies artificially ‘salami-slice’ some disorders into subgroups, at the expense of other ultra rare diseases, such as progeria, which affects only a few hundred patients worldwide.

Opponents of widespread orphan designation fear that increasing numbers of orphan drugs could paralyse regulatory agencies, as they depend vastly on user fees (USD 2.17 million per user fee at the FDA). On the other hand, the present director of the OOPD believes that regulatory agencies are capable of adapting to new trends in drug development. In her opinion, whether for very rare diseases or for cancer subgroups, “the more orphan drugs we see, the better”.

FDA authorises oral suspension of Purixan®
On 28 April 2014, Nova Laboratories' drug Purixan® (mercaptopurine) gained FDA approval as part of a combination treatment for acute lymphoblastic leukaemia (ALL). Originally produced as a 50 mg tablet dose, the drug has been reformulated as an oral suspension, offering accurate dose delivery to children, on a weight dependent basis.

ALL, one of the most common types of cancer in children, affects the bone marrow and white blood cells, causing anaemia, bleeding problems and infections. In addition to combination chemotherapy, Purixan® (Xaluprine® outside the US) contributes to patient survival.
For further information

Australia’s strict pay-for-performance scheme
Australia’s Pharmaceutical Benefits Advisory Committee (PBAC) has recommended listing cystic fibrosis treatment Kalydeco® (ivacaftor) and atypical haemolytic uraemic syndrome (aHUS) drug Soliris® (eculizumab) on the Pharmaceutical Benefits Scheme (PBS).

Under Australia’s pay-for-performance model, however, patients will be taken off the expensive treatment if their condition does not improve. Furthermore, pharmaceutical companies Vertex and Alexion who distribute Kalydeco® and Soliris®, respectively, must reimburse the government for costs incurred if patients do not respond to the treatment.

In an effort to improve drug quality and control public expenditure, policy makers in some countries, including Australia, have introduced pay-for-performance schemes, under which providers are rewarded for meeting healthcare delivery targets. The two companies do not agree to the PBAC’s decision and claim that patients will be unjustly deprived of potentially life-saving therapies. Patient advocacy group Cystic Fibrosis Australia further criticises PBAC’s recommendation, expressing disappointment that patients would have to interrupt Kalydeco® treatment under such conditions.
Read the press article

Political and Scientific News
Diagnosing and treating epilepsy in its rarest forms
A recent Nature Reviews article addresses the challenges of diagnosing and treating paediatric epilepsies. The International League Against Epilepsy (ILAE) recommends changes in epileptic seizure terminologies, in order to simplify and harmonise classification globally. The use of familiar and clear terms, such as ‘genetic’, ‘structural-metabolic’ and ‘unknown’, to describe the causes of epileptic seizures has been recommended. This is particularly relevant in resource-poor areas, where records are more likely to be descriptive.

Epilepsy is often misdiagnosed or under-diagnosed due to gaps in knowledge regarding epidemiological data and treatment. For instance, Dravet syndrome, a rare form of epilepsy, is not a focal epilepsy, though patients often present with focal-onset hemiclonic seizures. Misdiagnosis might result in harmful decisions concerning treatment. The review recommends the use of witness accounts of seizures through video Electroencephalography (EEG) or even telephone video recordings, particularly in situations where diagnosis is uncertain. These records will further contribute to the description and classification of paediatric epilepsies.

An increasing use of imaging and genetic diagnostic tools has significantly improved the management of epilepsy. Magnetic resonance imaging (MRI) enables specialists to gain considerable information, particularly on very young patients, and decide on appropriate surgery or further (genetic) diagnosis. In Dravet syndrome, an accurate genetic analysis will help the physician to select optimal treatment. Additionally, uncovering the genetic nature of the mutation causing the disease will enable parents to know whether the mutation is inherited or spontaneous in this child. In the case of de novo mutations, the disease will not, usually, affect siblings.

Regarding treatment, antiepileptic (AED) drugs are increasingly developed for paediatric use. Regulatory authorities recognise the need to conduct early risk-benefit analyses of AEDs in limited paediatric populations. Stiripentol for instance, though unrelated to other anticonvulsants, is reported to reduce severe convulsions in Dravet syndrome patients. A number of AEDs, including drugs prescribed off-label, benefit small numbers of patients and could receive orphan drug designation.

Overall, the multi-factor nature of paediatric epilepsy, including rare forms such as Dravet and Sturge-Weber syndromes, and their consequences on infant development require multi-disciplinary and personalised therapeutic management. The UK’s National Institute of Health and Care Excellence (NICE) has issued guidelines, offering evidence-based advice on the diagnosis and management of epilepsies. The authors of the review recognise the need for flexible guidelines, adapted to different populations, in order avoid placing resource-poor populations at a disadvantage. They further highlight the importance of managing epilepsy as early as possible in order to ensure long term management of the disease, into adulthood.



Call for projects Preclinical Research in Rare Diseases
The Rare Disease 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 pilot programmes at the interface between proof of concept in vivo obtained in rodents and development of a clinical application in humans to improve the well-being of patients. The Foundation will enable winners to develop their projects within structures known for their expertise, in accordance with European regulations.
Deadline for pre-proposals submission: 16 April, 2014.
Deadline for full proposals: 25 June, 2014.
For further details

The Histiocytosis Association 2014 Request for Research Proposals (RFRP)
Each year, the Association awards individual research grants in an effort to promote better treatments and a cure for histiocytic disorders. The association aims to foster partnership in combating histiocytic disorders.
Application deadline: 1 July, 2014
For further details

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

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

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

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


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


    News from the Patients' Associations
    Last year, Dr Nicolas Sireau set up Findacure, a charity to help patients with fundamental diseases. The project was inspired by Dr Sireau’s personal experience of trying to find a cure for Black Bone Disease (Alkaptonuria), a rare genetic disease affecting his children. Ten years of fighting to raise funds, setting up an international research consortium and organising trials made him acutely aware of the uphill struggle facing all patients with such neglected diseases. A disease such as Black Bone Disease is not just a medical curiosity. The study of rare diseases is fundamental to understanding human biology and common diseases. Researchers have demonstrated that it is an excellent model to understand osteoarthritis, a very common disease.

    For further information on Findacure’s fundraising campaign.
    (One of Findacure's donors will match-fund every dollar raised).


    Courses & Educational Initiatives

    EURORDIS Summer School for Patient Advocates In Clinical Trials & Drug Development
    Date: 2-6 June, 2014
    Venue: Barcelona, Spain

    The EURORDIS Summer School was initiated in 2008 to contribute to empowering people living with rare diseases. This four-day course provides training in aspects of medical development and EU regulatory processes where patients' representatives can be involved.
    For further information

    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). This one-day workshop is organised into four 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.
    For further information

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

    International Summer School: Rare diseases and orphan drug registries
    Date: 15-19 September 2014
    Venue: Rome, Italy

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

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

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


    What's on Where?

    The European Human Genetics Conference 2014
    Date: 31 May - 3 June, 2014
    Venue: Milan, Italy

    The European Human Genetics Conference (now in its 47th year) is a forum for all workers in human and medical genetics to review advances and develop research collaborations.
    For further information

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

    Organised by FEDER, the Spanish Alliance for Rare Diseases.
    For further information

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

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

    Narrative Medicine: Consensus Conference & Second International Congress
    Date: 11-13 June, 2014
    Venue: Rome, Italy

    The National Centre for Rare Diseases Centre of the National Institute of Health organises two events focusing on Narrative Medicine:
    - 11th-12th-13th June 2014 Consensus Conference ‘Recommendations for the use and implementation of Narrative Medicine at clinical and care level, for the management of rare and chronic degenerative diseases’. The President of the Jury will communicate the Recommendations on the occasion of the Second International Congress ‘NARRATIVE MEDICINE AND RARE DISEASES’.
    - 13th June 2014: Second International Congress 'NARRATIVE MEDICINE AND RARE DISEASES'.
    For further information

    LGDA Patient - Family Conference
    Date: 13-14 June, 2014
    Venue: Texas, US

    The Lymphangiomatosis & Gorham's Disease Alliance (LGDA) will hold its inaugural Patient - Family Conference. This milestone event will bring together, for the very first time, patients, families, and experts in the field from around the world.
    For further information

    Euromit 2014 - International Meeting on Mitochondrial Pathology
    Date: 15-19 June, 2014
    Venue: 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 around 700 molecular scientists, clinicians and representatives of the healthcare industry to attend.
    For further information

    Updates on Neurometabolic Disorders
    Date: 19-20 June 2014
    Venue: Amsterdam, The Netherlands

    Expert international and national speakers will present updates and new trends in neurometabolic disorders and their link to cancer.
    For further information

    29th Annual Annual Huntington's Disease Society of America's (HDSA) Convention
    Date: 20-22 June, 2014
    Venue: Louisville, US

    This year’s convention will include numerous workshops to help patients, caregivers, and clinicians learn more about the behavioural, cognitive, physical, and legal issues associated with caring for a person with Huntington's disease.
    For further information

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

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

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

    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 revolutionise 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
    Venue: Haifa Israel

    This bi-annual meeting is organised by the European Working Group on Gaucher Disease 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

    2014 Annual Connect Conference
    Date: 26-29 June, 2014
    Venue: Chicago, US

    PPMD's 20th Annual Connect Conference started as a few dozen parents and a handful of experts gathered to discuss and learn all they could about Duchenne. The event has grown into a meeting where families, physicians, researchers, industry leaders, and experts of all kinds gather to speak face-to-face about Duchenne. It is your opportunity to share support and build partnerships. The PPMD Annual Connect Conference helps shape our understanding of the Duchenne landscape.
    For further information

    Retina International 2014 - 18th World Congress of Ophthalmology
    Date: 27-29 June, 2014
    Venue: Paris, France

    French and International scientists will provide a full overview of the latest medical advances in eye diseases. Some sessions will be dedicated to DMLA, retinis pigmentosas, optic neuropathies and USHER syndrome. Establishing a balance of clinical trials around the world and discussing the perspective of future trials, RETINA 2014 congress will enable you to benefit from the latest updates and contribute to planning for the future.
    For further information

    Day To Day With SMA
    Date: 28-29 June, 2014
    Venue: Warwickshire, UK

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

    2014 World Tuberous Sclerosis Complex (TSC) Conference
    Date: 3-6 July, 2014
    Venue: Washington DC, US

    The TS Alliance is an important resource for people with TSC. The 2014 event will support an expanded, worldwide TSC community. Over 1,100 attendees are expected from across the globe, including families and individuals with TSC, caregivers, healthcare professionals and researchers.
    For further information

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

    The objective of the conference is to introduce the multifaceted nature of rare diseases. The conference, seminars and training sessions of this event aim to increase awareness regarding coordinated actions to improve the quality of life of patients with MPS and rare diseases in Poland and globally.
    For further information

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

    The 13th ICNMD will bring together experts to share knowledge and experience in the field of neuromuscular diseases. Physicians and scientists, involved in diagnosis, care, research in basic mechanisms and therapeutic approaches would greatly benefit from this event.
    For further information

    Myotubular Trust Family Conference
    Date: 12 July, 2014
    Venue: London, UK

    The Myotubular Trust wishes to invite anybody, whose life is affected by myotubular or centronuclear myopathy, to attend their Family Conference. The Conference is free-of-charge and provides a unique opportunity for delegates to meet other affected families and individuals, hear from the leading researchers in this field and discover some of the latest ideas about how to manage the condition.
    Booking form and agenda now available online.

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

    Developed jointly by the Bio-Ontologies and BioLINK special interest groups, Phenotype Day will bring together researchers from different disciplines to share information on phenotype resources and issues as well as experience in defining, representing, processing and using phenotype data.
    For further information

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

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

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

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

    25th European Dysmorphology Meeting
    Date: 10-12 September, 2014
    Venue: Le Bischenberg (20km west of Strasbourg), France

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

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

    HGV2014 will bring together approximately 180 delegates (selected on the basis of their abstract submission) in a workshop-style atmosphere, with 25 internationally recognized speakers.
    For further information

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

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

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

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

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

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

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

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

    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

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

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

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

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

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

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

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

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

    The French Angelman Syndrome Association (AFSA) will organise the Third Angelman Syndrome International Meeting, for researchers and clinicians working on neurosciences, gene therapy, neurological development impairment, and 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

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

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

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

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

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

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

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

    This third joint symposium on Neuroacanthocytosis addresses neurologists, interns, haematologists and biotechnologists working in the field of diagnostic, clinical and therapeutic management of patients affected by Neuroacanthocytosis and brain iron accumulation diseases. The scientific issues of this meeting will cover both the identification and characterisation of new aspects of this condition, as well as clinical developments.
    For Further Information

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

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

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

    Cilia 2014 will focus on (but not be limited to) recent advances in cilia structure and function, including trafficking, cilia and development, cilia in human genetic disease and cilia in infectious microorganisms. The event is organised by 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

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

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

    Commercial events

    Drug Development Primer
    Date: 5-6 June, 2014
    Venue: Boston, US

    Drug Development Primer is an intensive two-day course on the regulatory, commercial and scientific considerations required to successfully bring a drug to market. Discussion will focus on both small molecule and biologic products. Numerous case studies will be used to illustrate company decision-making processes, providing participants with a working knowledge of strategic development.
    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, manufacture, launch and supply sustainability, in order that manufacturers are guaranteed full and speedy reimbursement.
    For Further Information

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

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

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

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


    Media, Press & Publications
    The Voice of Rare Disease Patients: Experiences and Expectations of over 3,000 Patients
    A new EURORDIS book, The Voice of Rare Disease Patients: Experiences and Expectations of over 3,000 Patients on Rare Disease Patient Registries in Europe presents the results of an extensive consultation process, including a survey of over 3,000 European patients conducted by EURORDIS as part of the EU-funded EPIRARE project to build consensus and synergies for the EU registration of rare disease patients. Registries are instrumental tools for understanding the natural history of rare diseases, capturing unmet medical needs, gathering critical data for research, and tracking treatment benefits and risks. The survey results show that patients understand and value a comprehensive European approach to rare disease registries, strongly favouring EU-level regulation for registries. A European registry platform should be publicly funded and patients should be involved in all aspects of governance. Capacity-building is needed to ensure this patient involvement.

    Download the book here

    Rare Diseases in the Age of Health 2.0
    Written by an international authorship with experience and competence in the key areas of patient empowerment, healthcare and clinical knowledge management, healthcare inequalities and disparities, rare diseases and patient advocacy, this book highlights the opportunities and challenges of research and development for orphan disease medicines.

    The book can be purchased from Springer, Amazon.com or Amazon.co.uk

    Title: Rare Diseases in the Age of Health 2.0
    Series: Communications in Medical and Care Compunetics, Vol. 4, 2014
    Editors: Rajeev K. Bali, Lodewijk Bos, Michael Christopher Gibbons, Simon Ibell
    Publisher: Springer
    ISBN: 978-3-642-38642-8 (Print) 978-3-642-38643-5 (Online)


    OrphaNews, The Newsletter of the Rare Diseases Community.
    OrphaNews is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
    and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Ségolène Aymé
    Editor: Antonia Mills
    Editors for Scientific Content: Catherine Pouzat, Sophie Höhn
    Contact Us
    Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Barbara Cagniard, Helena Kaariainen, Lilian Lau, 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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