10 October 2012 print
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Going with the flow:
EUCERD's recommendation for improving the assessment of the Clinical Added Value of Orphan Medicinal Products encourages the creation of an Information Flow

Equitable and timely access to market-authorised orphan medicinal products is an ongoing issue for thousands of rare disease patients and their families across the European Union (EU). Large disparities in access exist between and even within the European Member State countries. Increasing cooperation between EU-level authorities and the Member States (MS) has been identified as a means of improving access to Orphan Medicinal Products (OMP) and reducing inequities. Global auditing firm Ernst & Young was mandated by the European Commission to identify and assess the possible options for the creation of a mechanism for the exchange of knowledge between the MS and European authorities on the scientific assessment of the relative effectiveness of orphan medicines and issued a report in December 2011. The European Commission consequently asked the European Union Committee of Experts of Rare Diseases (EUCERD) to make recommendations in the area of facilitating the exchange of scientific information on orphan medicinal products that would support the clinical assessment processes undertaken by the MS.

No need to reinvent the wheel...
The EUCERD recommendation involves the creation of an Information Flow between individual MS and between MS and the EU that would bridge existing knowledge gaps, especially at the time of marketing authorisation. This flow would fit into existing regulatory, clinical, Health Technology Assessment (HTA), pricing and reimbursement processes. The recommendation thus capitalises on existing mechanisms, procedures, and regulatory frameworks, and does not bring new obstacles to the assessment process. The EUCERD Recommendation emphasises the continuum of evidence generation that takes place during the life cycle of an individual OMP and the Information Flow would be harboured by the corresponding institution responsible during each particular point in time (see the diagram).

The EUCERD Recommendation Improving Informed Decisions Based on the Clinical Added Value of Orphan Medicinal Products (CAVOMP) Information Flow will ultimately accelerate access to approved orphan medicinal products, while encouraging pricing and reimbursement decisions based on the value of the OMP and promoting good medical practices throughout the EU. The Recommendation has been submitted to the European Commission.
Consult the EUCERD Recommendation for a CAVOMP Information Flow


EUCERD update
EUCERD gets a fresh look and updated website

The European Union Committee of Experts on Rare Diseases (EUCERD) has redesigned its website, allowing users easier access to the recommendations, documents and reports on EUCERD activities, including meetings and workshops, and links to related resources at the national, European and international levels. The website and logo overhaul have been financed under the three-year EUCERD Joint Action, for which more information can be found on the updated website.
Visit the updated EUCERD website


EU Policy News

DG Research
Biobanks for Europe: A challenge for governance
A new report, produced by DG Research with the participation of an interdisciplinary group of experts, looks at the regulatory and ethical challenges of international biobank research. In order to link individual biobanks together as part of a pan-European infrastructure supporting medical research and health care, an adequate governance framework needs to be put in place. The development of a biobank infrastructure is seen as critical in the field of rare diseases where difficulties accessing specific rare samples can hinder research. This expert report offers a set of recommendations for the effective governance of a pan-European biobank network.
Consult the report

Public consultation on the experience gained from five years of the Paediatric Regulation
It is estimated that at least half of all medicinal products used on paediatric patients have never specifically been tested on this population. The percentage is thought to be even higher for children with rare diseases. In this context, Regulation (EC) No 1901/2006 (the Paediatric Regulation), came into force in January 2007. The Paediatric Regulation seeks to stimulate research and development of medicines for use in children, ensure that medicines for children are appropriately tested and authorised, and improve information availability. Five years after the Paediatric Regulation came into being, the European Commission is preparing a general report presenting the experience acquired as a result of the application of the Paediatric Regulation and including an inventory of the medicinal products authorised for paediatric use since the regulation took effect. The Commission has released for public consultation the General Report on Experience Acquired as a Result of the Application of the Paediatric Regulation: Experience Acquired and Lessons Learnt. The deadline for public consultation for this report is 28 November 2012.
Learn more


National & International Policy Developments
Improving access to orphan drugs in Bulgaria and other Eastern European countries
A recent cross-sectional observational study appearing in the journal Health Policy evaluates the conditions that impact orphan drug availability in Bulgaria and other Eastern European countries. As of March 2011, only 16 of the 61 EU-authorised orphan drugs were reimbursed in Bulgaria. The authors observe that in Bulgaria:

All the other orphan drugs, being not reimbursed, are practically inaccessible for the individual patients because of their high price. Despite the increasing number of orphan drugs, which are being reimbursed in Bulgaria, in reality there is no significant improvement of the accessibility of treatment for rare diseases. Neither a national epidemiological registry nor expert centres for rare diseases exist. Regulation of alternative access to orphan drugs (e.g., compassionate use, off-label use) is also missing. In these conditions many patients are left without correct diagnosis, adequate treatment, follow-up and rehabilitation.

The system for determining pricing is proving detrimental to orphan drug availability. Bulgaria uses a history-based budget through which funds for orphan drug treatments are allocated annually based on the previous year’s calculated needs. Thus if the population of newly diagnosed patients grows, medicinal treatment shortages and access limitations also increase. The inclusion of new drugs in the country’s reimbursement scheme results from improved awareness for rare diseases among physicians and patient associations, as well as the intentions of pharmaceutical manufacturers to market their products in Bulgaria. The authors outline the flaws with the current EU pricing system: "Most EU member states compare the price requested by the manufacturer with the price in other countries. The United Kingdom has set up a system of profit control to constrain prices (although this system will be abolished in favour of a value-based pricing approach from 2013/14) and Sweden uses a system of public procurement at the regional level in order to maximise price competition. In Bulgaria, the mechanism of smallest value from a set of international reference prices reduces the opportunities for flexible solutions. The inclusion of reference countries with floating euro exchange rate makes the pricing of orphan drugs dependent on the macroeconomic indicators in these countries and thereby allowing serious fluctuations of the price. This is a specific reason for the reluctance of some companies to register prices of their orphan drugs in the small Eastern European non-Eurozone countries. Financial difficulties in one country may lead to lower prices in all referring ones. It should be also underlined that Member State authorities have little negotiating leverage since these medicines have no therapeutic alternative”.

Another important element that negatively impacts small countries is a lack of clinical data around the cost-effectiveness of rare disease medicinal products. Epidemiological rare disease registries are needed to improve knowledge in this area. Thus the authors call for a reformed orphan drug policy-making process that is transparent, and based on a convergence of medical, economic, ethical and social elements. The newly-released Recommendation of the European Union Committee of Experts on Rare Diseases on the Clinical Added Value of Orphan Medicinal Products (CAVOMP) Information Flow is intended to improve equity to orphan drug access in the EU Member States (see the Editorial).
Consult the PubMed abstract

Recommendations to improve orphan drug legislation in Europe based on the results of a Delphi policy study involving European orphan drug experts
Prompted by perceived changes to the political, social, economic and scientific landscapes since Regulation (EC) No 141/2000 (the Orphan Drug Regulation) came into effect, a new study makes the hypothesis that the legislation may be in need of refinement, taking such changes into account. Citing examples such as technological advancements in genetics that cause “a disaggregation of prevalent diseases into many distinct rare conditions, making orphan status increasingly more common” the case is made for the need for an evaluation of the current orphan drug policies. To accomplish this, the authors surveyed a number of European orphan drug experts, including academics, policy makers, members of the biopharmaceutical industry, and patient organisation representatives, via a two-rounded policy Delphi study that examined key elements of the Orphan Drug Regulation, including orphan designation, market authorisation, market exclusivity, compassionate use, assistance and guidance, accelerated approval, and related issues. While the results of this study, published in the journal Health Policy, show that orphan drug policies in Europe “have not outlived their usefulness”, the authors make several policy recommendations based on the survey findings, including reducing the period of marketing exclusivity for products deemed “sufficiently profitable”; possibly introducing priority review vouchers to spur the development of new orphan drugs; and extending further assistance and guidelines for small population studies. To help ease inequities in access to orphan drugs between EU countries, the authors suggest regulating compassionate use of (orphan) drugs at the European level and installing a European reimbursement assessment procedure that provides assistance to the Member States.
Consult the PubMed abstract

New scheme in England allows researchers to access National Health Service patient records
In England, a government-backed initiative allows researchers unprecedented access to anonymised patient health records. The Clinical Practice Research Datalink (CPRD) is a new observational data and interventional research service of the National Health Service (NHS), jointly funded by the NHS National Institute for Health Research (NIHR) and the Medicines and Healthcare products Regulatory Agency (MHRA). The CPRD is “… designed to maximise the way anonymised NHS clinical data can be linked to enable many types of observational research and deliver research outputs that are beneficial to improving and safeguarding public health”. Data confidentiality is a top priority for the new service and several mechanisms are in place to protect patient privacy. Access to patient data could help rare disease researchers advance knowledge and understanding of rare conditions.
Learn more

European court rules that Italian law prohibiting pre-implantation diagnosis violates human rights
The European Court of Human Rights in August ruled that an Italian law prohibiting a couple from undertaking pre-implantation embryo diagnosis is in violation of Article 8 (right to respect for private and family life) of the European Convention on Human Rights. The couple discovered that they were both carriers of the disease following the birth of an affected child. Italy is amongst a small number of countries in Europe that prohibits pre- implantation diagnosis. According to several news reports, Italian policy makers are calling for reform to the law in the wake of the legal wrangle.
Learn more about the decision of the European Court of Human Rights

Other European news
First Wellcome Trust Pathfinder Awards encourage academic-industry collaboration for two rare diseases
In March of this year, OrphaNews Europe reported on the launch of a new funding mechanism created by global charitable foundation the Wellcome Trust. The Pathfinder Awards support academic-industry partnerships dedicated to early-stage applied research in the field of rare and neglected diseases. Open to international participation, the Pathfinder Awards seek to kick-start pilot research initiatives showing potential for developing innovative medicinal products for rare or neglected diseases. Last month, the first two awards were granted. The first award goes to a collaborative effort involving researchers from the University College London and pharmaceutical giant Lilly to develop a line of human stem cells to better understand the underlying mechanisms of neurodegeneration with brain iron accumulation (NBIA), a group of neurodegenerative disorders characterised by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation in the brain and the presence of axonal spheroids. The second award has been granted to an academic-industry team from the Structural Genomics Consortium at the University of Oxford and from Pfizer's Rare Diseases Research Unit to investigate methods of restoring normal metabolism and preventing the progression of the disease homocystinuria, a severe, childhood-onset disorder of cystathionine beta-synthase deficiency, characterised by the multiple involvement of the eye, skeleton, central nervous system, and vascular system.
Learn more about the Pathfinder Awards

Other International News
Pinpointing rare disease prevalence in Taiwan
A recent paper appearing in Research in Developmental Disabilities describes efforts to capture epidemiological data for rare diseases in Taiwan. Experts agree that in order for countries to organise rare disease policies and resources, data on the numbers and kinds of diseases in the population are crucial. The prevalence definition for rare diseases is less than 1 in 10,000 in Taiwan. The authors of this study analysed data from Taiwan’s rare disease disability registry, created in the country’s social welfare system in 2002. They found that the number of registered rare disease patients has soared from 53 to 1710 between 2002 and 2011. The number of rare diseases has increased from 93 to 193 during the same time period. The authors concede that precise prevalence was difficult to determine from the registry data and suggest that the public health system needs to strengthen efforts to monitor and measure rare diseases.
Consult the PubMed abstract
Learn more about rare diseases in Taiwan

Guidance Documents and Recommendations
Recommendations for the management of several paediatric cancers in free access
A special free-access supplement of the Journal of Pediatric Hematology/Oncology provides recommendations for the management of several rare cancers in children and young adults - including thyroid carcinoma, pancreatoblastoma, melanomas, ovarian and testicular sex cord-stromal tumours, neuroendocrine tumours, gastrointestinal stromal tumours, desmoplastic small round-cell tumours, and colorectal carcinoma. All the childhood cancers are rare.
Consult the supplement

Barrett esophagus: international consensus statements for management of Barrett's dysplasia and early-stage esophageal adenocarcinoma
Consult the PubMed abstract
To read more about "Barrett esophagus"

Gastroenterology ; 336-46 ; August 2012
Bioinformatics, Registries and Data Management
MeSH Concepts yield more precise results for rare disease Medline information retrieval
The rapidly increasing volume of biomedical and related literature spurs the National Library of Medicine (NLM) to undertake endeavours designed to improve access to biomedical information through PubMed. The evaluation of ranking and querying strategies for the PubMed search engine and the development of a disease sensor for facilitating access to trustworthy disease-related information through PubMed are recent efforts. Some twenty-eight institutes worldwide are “devoting efforts to the development of web tools designed to assist users in quickly and efficiently searching and retrieving relevant publications from Medline”. An article appearing in the Journal of the Medical Library Association describes a French study that takes 54 rare/chronic diseases to assess the benefit of Medical Subject Headings (MeSH) Concepts for indexing and information retrieval. The authors explain that the “underlying structure of the Medical Subject Headings (MeSH) Thesaurus has changed from a term-based system to a concept-oriented system to make it more compatible with the Unified Medical Language System (UMLS). In its 2011 version, the MeSH Thesaurus contains 26,142 Descriptors, 83 Qualifiers, 25,801 Entry Terms, 200,676 Supplementary Concepts, and 317,554 Concepts”. The study reveals that “higher retrieval precision can be obtained with queries based on MeSH Concepts rather than MeSH Descriptors, which is the current default”. Thus this study implies that MeSH Concepts can yield more precise searches in the area of rare/chronic diseases.
Learn more

Screening and Testing
Special issue of the Cancer Journal devoted to genetic testing and counselling for cancer
Volume 18 (July/August 2012) of the Cancer Journal offers readers a special issue on genetic counselling for cancer. Besides articles addressing current topics in cancer genetic counselling, the journal features articles on genetic testing by specific cancer site (skin, endocrine system, ovary, et cetera).
View the Table of Contents

Integrated genome-phenome analyzer automates clinical correlation in whole genome and exome sequencing
A new commercially available tool from Massachusetts-based SimulConsult has been designed to automate the clinical correlation step in the interpretation of whole genome and exome sequencing. The Genome-Phenome Analyzer “integrates genome analysis and comparison of the patient’s clinical findings (including family history, pertinent positives & negatives and onset) and lab results to the 'phenome', the collection of phenotypes of known diseases. The result is the ability to assess and prioritize which gene variants are most likely to account for the clinical picture”. SimulConsult, founded by former Children's Hospital Boston Pediatric Neurologist, Michael Segal, MD PhD, is considered a leader diagnostic decision support in neurology and genetics for clinicians. Its core diagnostic decision product is used worldwide and is part of case-based education for child neurology.
Learn more


New Syndromes

A novel congenital myopathy with specific biopsy features and dominant mutation of CCDC78
The authors describe a family with five members suffering from a new congenital myopathy characterised by neonatal hypotonia, distal weakness, excessive fatigue, prominent myalgias, mild-to-moderate overall motor impairment with preserved ambulation, and mild cognitive involvement. Muscle biopsy shows prominent internal nuclei and atypical cores. The affected members of this family carry a CCDC78 mutation transmitted in an autosomal dominant pattern.
Consult the PubMed abstract

Am J Hum Genet ; 365-71 ; 10 August 2012
A 17p13.1 microdeletion syndrome inducing microcephaly, intellectual disability, distinctive facial features and body posture
The authors report on two unrelated patients carrying a microdeletion in the distal region of 17p13.1 and sharing similar clinical features, i.e. microcephaly, mild developmental delay, intellectual disability, generalized joint laxity, and a body posture with knee and elbow flexion and hands held in midline. They also present with particular facial features including long midface, narrow forehead, deep-set eyes, high nasal bridge, underdeveloped cheekbones, open mouth secondary to low facial tone, retrognathia with overbite, and protruding ears. The deletions identified here are similar in size and position and the authors conclude that they are facing a new microdeletion syndrome.
Consult the PubMed abstract

Am J Med Genet A ; 1832-6 ; August 2012
Skeletal dysplasia, facial characteristics and developmental delay: a new syndrome resembling Desbuquois dysplasia
Seven unrelated males presenting with skeletal dysplasia, particular facial features and developmental delay are described by the authors. The osseous anomalies are patellar dislocation, short tubular bones, mild metaphyseal changes, brachymetacarpalia with stub thumbs, short femoral necks, shallow acetabular roofs and platyspondyly. The facial characteristics encompass a flattened midface with broad nasal bridge, cleft palate or bifid uvula, and synophrys. As for the cognitive developmental delay, it appears during the pre-school years with a shortened attention span and can be partly masked by a friendly behavior. Given that this phenotype resembles that of Desbuquois dysplasia, the authors think that it is possible that other patients with these clinical features have previously been described as having some forms of Desbuquois dysplasia.
Consult the PubMed abstract

Am J Med Genet A ; 1815-22 ; August 2012
Microcephaly, intrauterine and postnatal severe growth retardation, and minimal skeletal dysplasia in two children
The authors report on two children born to consanguineous parents and presenting with profound microcephaly, intrauterine and postnatal severe growth retardation, and minimal skeletal dysplasias. They share the same facial features: absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular microretrognathia. Brain imaging exhibits extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormal cerebral ventricular system, abnormally shaped hippocampus and proportionately small cerebellum and brainstem. Having ruled out the diagnoses that may correspond to some of the symptoms mentioned above, the authors think that these children suffer from a new syndrome.
Consult the PubMed abstract

Am J Med Genet A ; 1823-31 ; August 2012

New Genes

Familial thoracic aneurysm and dissection: TGFB2 mutations induce a syndromic form occurring as part of diseases like Marfan or Loeys-Dietz syndromes
Consult the PubMed abstracts
To read more about "Familial thoracic aneurysm and dissection"

Nat Gen ; 916-921; 922-7 ; 8 July 2012
Potocki-Shaffer syndrome: translocations disrupting PHF21A are associated with intellectual disability and craniofacial anomalies
Consult the PubMed abstract
To read more about "Potocki-Shaffer syndrome"

Am J Hum Genet ; 56-72 ; 13 July 2012
Wiedemann-Steiner syndrome: MLL haploinsufficiency disturbs epigenetic regulation of chromatin
Consult the PubMed abstract
Am J Hum Genet ; 358-64 ; 10 August 2012
Osteogenesis imperfecta type 5 is due to mutation in the 5’-UTR of IFITM5
Consult the PubMed abstracts
Am J Hum Genet ; 343-8; 349-57 ; 10 August 2012
Nephronophtisis-associated ciliopathy: ZNF423 and CEP164 mutations link renal ciliopathies to DNA damage response
Consult the PubMed abstract
To read more about "Nephronophthisis-associated ciliopathy"

Cell ; 533-48 ; 3 August 2012
Late-onset autosomal recessive medullary cystic kidney disease: FAN1 mutations tie chronic kidney failure to defective DNA damage repair
Consult the PubMed abstract
To read more about "Late-onset autosomal recessive medullary cystic kidney disease"

Nat Genet ; 910-5 ; August 2012
Weill-Marchesani syndrome: LTBP2 mutations strengthen the hypothesis of a disruption in the extracellular matrix
Consult the PubMed abstract
To read more about "Weill-Marchesani syndrome"

Hum Mutat ; 1182-7 ; August 2012
Colobamatous microphtalmia: a mutation in ODZ3 highlights its role in the early development of the human eye
Consult the PubMed abstract
To read more about "Colobomatous microphthalmia"

Genet Med ; Epub ahead of print ; 5 July 2012
Persistent hyperplastic primary vitreous: a mutation in ATOH7 causes a recessive form etiologically related to nonsyndromic congenital retinal nonattachment
Consult the PubMed abstract
To read more about "Persistent hyperplastic primary vitreous"

Hum Mol Genet ; 3681-94 ; 15 August 2012
Retinitis pigmentosa: an OFD1 mutation causes the severe form RP23 thus joining retinal ciliopathies group
Consult the PubMed abstract
To read more about "Retinitis pigmentosa"

Hum Mol Genet ; 3647-54 ; 15 August 2012
Primary cutaneous diffuse large B-cell lymphoma, leg type: a specific MYD88 mutation however not present in all cases
Consult the article via PubMed
To read more about "Primary cutaneous diffuse large B-cell lymphoma, leg type"

J Invest Dermatol ; 2118-20 ; August 2012

Research in Action

Fundamental Research
Osteogenesis imperfecta types 1, 2, 3, and 4: collagen mutations impair cardiopulmonary function in a bone-independent manner
Consult the PubMed abstract
To read more about "Osteogenesis imperfecta"
To read more about "Osteogenesis imperfecta type 1"
To read more about "Osteogenesis imperfecta type 2"
To read more about "Osteogenesis imperfecta type 3"
To read more about "Osteogenesis imperfecta type 4"

Hum Mol Genet ; 3535-45 ; 15 August 2012
Systemic sclerosis: a mouse model mimicking the conditions responsible for pulmonary arterial hypertension
Consult the PubMed abstract
To read more about "Systemic sclerosis"

Ann Rheum Dis ; 1382-7 ; August 2012
Amyotrophic lateral sclerosis: overexpressing the SMn protein in mSOD1 mice delays but does not halt the loss of motor neurons
Consult the PubMed abstract
To read more about "Amyotrophic lateral sclerosis"

Hum Mol Genet ; 3421-34 ; 1 August 2012
Charcot-Marie-Tooth disease type 4J: neuronal expression of Fig4 is both necessary and sufficient to prevent spongiform neurodegeneration
Consult the PubMed abstract
To read more about "Charcot-Marie-Tooth disease type 4J"

Hum Mol Genet ; 3525-34 ; 15 August 2012
Oculocerebrorenal syndrome: the localization and function of the OCRL protein suggest an involvement of the primary cilium
Consult the PubMed abstract
To read more about "Oculocerebrorenal syndrome"

Hum Mol Genet ; 3333-44 ; 1 August 2012
Autosomal dominant lateral temporal lobe epilepsy: a rat model for Lgi1-related epilepsies
Consult the PubMed abstract
To read more about "Autosomal dominant lateral temporal lobe epilepsy"

Hum Mol Genet ; 3546-57 ; 15 August 2012
Huntington disease: PGC-1α induction virtually eliminates huntingtin aggregation and ameliorates neurodegeneration in a mouse model
Consult the PubMed abstract
To read more about "Huntington disease"

Sci Transl Med ; 142ra97 ; 11 July 2012
Clinical Research
Idiopathic aplastic anemia: a thrombopoietin mimetic associated with multilineage hematologic responses in some patients with refractory severe form
Consult the PubMed abstract
To read more about "Idiopathic aplastic anemia"

N Engl J Med ; 11-19 ; 5 July 2012
Graft versus host disease: inhibition of lymphocyte trafficking reduces incidence of acute visceral forms without major adverse effects
Consult the PubMed abstract
To read more about "Graft versus host disease"

N Engl J Med ; 135-45 ; 12 July 2012
Prader-Willi syndrome: beneficial effects of GH treatment on cognitive disorders in children
Consult the PubMed abstract
To read more about "Prader-Willi syndrome"

J Clin Endocrinol Metab ; 2307-14 ; July 2012
Acquired hemophilia management: results from the European Acquired Haemophilia (EACH2) Registry
Consult the PubMed abstracts
To read more about "Acquired hemophilia"

Blood ; 39-46; 47-55 ; 5 July 2012
POEMS syndrome: autologous stem cell transplantation improves long-term outcome
Consult the PubMed abstract
To read more about "POEMS syndrome"

Blood ; 56-62 ; 5 July 2012
Beta-thalassemia major: a safe and efficient tritherapy as preparative regimen of allogeneic hematopoietic stem cell transplantation
Consult the PubMed abstract
To read more about "Beta-thalassemia major"

Blood ; 473-6 ; 12 July 2012
Idiopathic and/or familial pulmonary arterial hypertension and hyperthyroidism: a rather frequent association that should be detected early
Consult the PubMed abstract
To read more about "Idiopathic and/or familial pulmonary arterial hypertension"

J Clin Endocrinol Metab ; 2217-22 ; July 2012
Achondroplasia: lung function, upper airway and sleep should be regularly checked in affected children
Consult the PubMed abstract
To read more about "Achondroplasia"

Am J Med Genet A ; 1987-93 ; August 2012
Ataxia-telangectasia does not lead to increased risk for birth defects or adverse pregnancy outcomes other than those due to vascular lung anomalies
Consult the PubMed abstract
To read more about "Ataxia-telangiectasia"

Am J Med Genet A ; 2009-14 ; August 2012
Bullous pemphigoid: increase of incidence during the last 15 years in France with a high standardized mortality ratio
Consult the PubMed abstract
To read more about "Bullous pemphigoid"

J Invest Dermatol ; 1998-2004 ; August 2012
Stem Cells

Congenital erythropoietic porphyria: metabolic correction obtained in erythroid cells derived from corrected induced pluripotent stem cells
Consult the PubMed abstract
To read more about "Congenital erythropoietic porphyria"

Am J Hum Genet ; 109-21 ; 13 July 2012
Amyotrophic lateral sclerosis: motor neurons generated from patients-derived IPSc used to study the mechanisms of the disease
Consult the PubMed abstract
To read more about "Amyotrophic lateral sclerosis"

Sci Transl Med ; 145ra104 ; 1 August 2012
Gene Therapy
Facioscapulohumeral dystrophy: DUX4 gene silencing through RNA interference is myoprotective in a mouse model
Consult the PubMed abstract
To read more about "Facioscapulohumeral dystrophy"

Mol Ther ; 1417-23 ; July 2012
Mucopolysaccharidosis type 7: efficiency of vectors used for gene therapy can be impacted by disease manifestations
Consult the PubMed abstract
To read more about "Mucopolysaccharidosis type 7"

Mol Ther ; 1393-9 ; July 2012
Leigh syndrome: fatal breathing dysfunction in a mouse model with NDUFS4 inactivation, partially corrected by a gene therapy strategy
Consult the PubMed abstract
To read more about "Leigh syndrome"

J Clin Invest ; 2359-68 ; July 2012
Transmissible spongiform encephalopathies: neurodegeneration is due to translational repression by eIF2α-P
Consult the PubMed abstract
To read more about "Transmissible spongiform encephalopathies"

Nature ; 507-11 ; 6 May 2012
Therapeutic Approaches
Muscle dystrophy and dilated cardiomyopathy: rapamycin and its analogs improve cardiac and skeletal muscle function in mice
Consult the PubMed abstracts
To read more about "Spinocerebellar ataxia type 14"
To read more about "Autosomal dominant limb-girdle muscular dystrophy type 1B"
To read more about "Familial dilated cardiomyopathy with conduction defect due to LMNA mutation"

Sci Transl Med ; 144ra102; 144ra103 ; 25 July 2012
Retinitis pigmentosa: restoration of visual responses in mice models after intraocular injection of a synthetic small molecule
Consult the PubMed abstract
To read more about "Retinitis pigmentosa"

Neuron ; 271-82 ; 26 July 2012
Pelizaeus-Merzbacher disease: a cholesterol-enriched diet enhances oligodendrocyte number and function and prevents disease progression in mice
Consult the PubMed abstract
To read more about "Pelizaeus-Merzbacher disease"

Nat Med ; 1130-5 ; July 2012
Idiopathic and/or familial pulmonary arterial hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid
Consult the PubMed abstract
To read more about "Idiopathic and/or familial pulmonary arterial hypertension"

Circulation ; 455-67 ; 24 July 2012
X-linked creatine transporter deficiency: cyclocreatine treatment improves cognitive abilities in a newly developed mouse model
Consult the PubMed abstract
To read more about "X-linked creatine transporter deficiency"

J Clin Invest ; 2837-46 ; 1 August 2012
Diagnostic Approaches

Cornelia de Lange syndrome: identification of a prenatal profile
Consult the PubMed abstract
To read more about "Cornelia de Lange syndrome"

Am J Med Genet A ; 1848-56 ; August 2012
Coffin-Siris syndrome: a diagnostic approach
Consult the PubMed abstract
To read more about "Coffin-Siris syndrome"

Am J Med Genet A ; 1865-76 ; August 2012

Patient Management and Therapy

Ehlers-Danlos syndrome, hypermobility type: how to assess and treat pain and fatigue?
Consult the PubMed abstract
To read more about "Ehlers-Danlos syndrome, hypermobility type"

Am J Med Genet A ; 2055-70 ; August 2012
Intellectual disability: a digital tool to enhance diagnosis and care for rare diseases
Consult the PubMed abstract
Orphanet J Rare Dis ; 7(1):47 ; 23 July 2012

Orphan Drugs

Regulatory News
First paediatric-specific dosage form approved for a paediatric cancer in the USA
In the USA, the Food and Drug Administration approved Afinitor Disperz (everolimus tablets for oral suspension), a new paediatric dosage form of the anti-cancer drug Afinitor (everolimus) used to treat subependymal giant cell astrocytoma. Afinitor Disperz (Novartis) is the first approved paediatric-specific dosage form developed for the treatment of a paediatric tumour.
Learn more

Political and Scientific News
Is the special status assigned to orphan drugs justified?
A recent article appearing in Drugs contends that because there does not seem to be a distinct societal preference for treating rare diseases, then there is no real rationale for assigning special market access status to orphan drugs intended to treat rare conditions. While evidence does suggest that society assigns a greater value to disease severity, this element is not exclusive to rare conditions. Moreover, the authors contend that the incentives created in Europe via Orphan Drug Regulation (EC) No 141/2000 and similar mechanisms in other parts of the world, designed to encourage the development of rare disease medicinal products, have in fact created market failures, including the “salami slicing” of common diseases “to create more rare therapeutic indications and price monopolisation". The authors propose other venues for facilitating orphan drug development and market access, including the optimisation of research and development, and instruments to control pricing, such as patent auctions, dose-response studies, or advance purchase commitments. While there are certainly some costly rare disease treatments currently on the market, not all of the orphan drugs come with a high price tag.
Consult the PubMed abstract

Fabry disease: positive preliminary findings after switching from agalsidase beta (Fabrazyme) to agalsidase alfa (Replagal) in Japanese patients
Consult the PubMed abstract
To read more about "Fabry disease"

Genet Med ; 779-86 ; September 2012


Myotubular Trust issues fifth call for projects to international applicants

The Myotubular Trust (Registered Charity No: 1137177) was set up in 2006 to raise money for research to find a cure and/or treatment for myotubular myopathy. There are three genetically distinct forms of Myotubular Myopathy, the commonest and most severe being X-linked and typically presenting in the newborn period with associated breathing and swallowing difficulties in addition to general muscle weakness. In recent years, the Myotubular Trust has awarded research grants/fellowships for projects exploring gene therapy for X-linked myotubular myopathy and pathophysiology; membrane trafficking and T tubule structure and function in a canine model of centronuclear myopathies; deciphering the molecular pathway involving centronuclear myopathy genes; gene therapy for autosomal dominant centronuclear myopathy by Transplicing; next generation sequencing to tackle centronuclear myopathies; and secondary pathogenic mechanisms.

A Fifth call for projects
The Myotubular Trust is holding a fifth call for research projects that will help find a cure and/or a treatment for any of the three types of myotubular myopathy (congenital X-linked recessive; congenital autosomal recessive; autosomal dominant), focusing on research that would not generally be funded by public or industrial funding sources. This call is open to international applications and may be made for either a project grant or a nonclinical fellowship in basic science for which the scientist has identified a group to work with. Completed applications are due by Friday 11 January 2013.
Learn more


News from the Patients' Associations
When Mother knows best ...
The international association Ring 14 is a non-profit organisation for families with children affected by Ring chromosome 14 syndrome, a rare condition characterised by intellectual deficit, retinal and skin pigmentation disorders, seizures, and dysmorphic features. A Mother's Guide to Good Health and Seizure Control is a recent addition to the store of information available on the the association’s website. As the title suggests, this document is a non-scientific, non-medical guide written by the mother of an affected child. The author shares with readers the results of her experience over eight years of daily life (and numerous medical crises) with her affected daughter, now aged 10. The guide offers suggestions on nutritional issues, respiratory considerations, seizures, vaccinations, health indicators, puberty, medical care, related medical issues, advocacy, siblings, and more - all written in a clear, straight-forward style, through which shines one mother’s intentions to help other parents learn from her own hard-won experience.
Learn more

To read more about "Ring chromosome 14"


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 2013 course is now available.
For further details

Online Master of Science in Haemoglobinopathy
A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy – such as counsellors, clinical psychologists, nurse specialists and midwives.
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The European School of Haematology distance learning tools
The European School of Haematology (ESH) is a non-profit organisation founded in 1986. Its mission is continuous medical education in Haematology and the fields related to Haematology. ESH organises conferences throughout Europe and on other continents. It also produces distance learning tools of which many are freely available on the ESH website: These include: The Curriculum on Iron Metabolism and Related Disorders: This is a comprehensive curriculum comprising webcasted lectures, videos, interviews, round table discussions etc. The faculty is composed of distinguished international experts in the field. Webcasted conferences are also freely available on the website, including topics such as: Diagnosis and Management of Rare Anaemias; Haemoglobin Disorders: Laboratory Diagnosis and Clinical Management; World Cord Blood Congress, and more.
Goldrain Courses in Clinical Cytogenetics and Prenatal Genetic Diagnosis
The Goldrain Prenatal Genetic Diagnosis, tentatively course scheduled from 6-12 October 2013 at the Goldrain Castle in South Tyrol (Italy), is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination.
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Orphan Academy 2012 Programme
The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
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EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
For further details


What's on Where?

2nd Annual U.S. Conference on Rare Diseases and Orphan Products
Date: October 22-24 2012
Venue: Washington DC, USA

Of interest to: researchers from academia and drug and device companies; patient organizations and those interested in creating one; senior managers from drug and device companies interested in rare diseases; investors focused on the future of orphan product development ; policy experts who are concerned about federal or state policies that affect patients with rare diseases; providers of services to the rare disease community, including insurance providers and healthcare professionals; government officials responsible for rare disease research and orphan product oversight.
For further details

3rd Pan-European Conference on Haemglobinopathies and Rare Anaemias: Towards the Future
Date: 24–26 October 2012
Venue: Limassol, Cyprus

The Thalassaemia International Federation is delighted to announce the organisation of the 3rd Pan-European Conference, held under the auspices of the Cyprus Presidency and in close collaboration with the Cyprus Ministry of Health. The conference will bring together stakeholders to discuss avenues of action to tackle the growing public health burden of chronic and rare diseases in Member States and the EU.
For further details

The Second Joint International Symposium on Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation
Date: 26–27 October 2012
Venue: Ede, Netherlands

Topics will include autophagy; clinical studies; erythropoiesis; new genes; pathophysiology; protein-misfolding; treatment strategies and round table discussions with patient organisations and basic and clinical researchers.
For further details

41st European Society of Clinical Pharmacy Symposium: Personalised and Safe Therapy
Date: 29-31 October 2012
Venue: Barcelona, Spain

Featuring a session on Cross-border Healthcare and Rare Diseases. Other topics include Orphan drugs and ultra orphan drugs; European perspective of the clinical trials; Modeling and simulation in the development of new drugs by the pharmaceutical industry; Pharmacogenetics and pharmacists; Advances in personalized therapy in oncology; Approach to the polymedicated patient; Cost containment measures in hospital pharmacy services: the role of the hospital pharmacy services in the rational use of drugs, and more.
For further details

6th International Workshop on Alkaptonuria
Date: 1-2 November 2012
Venue: Piestany, Slovakia

This one and a half day meeting will include talks from international experts in alkaptonuria (AKU) research. Sessions will include Organ involvement in ochronotic arthropathy; Ins and outs in micro-studies of AKU arthropathies; Homogentisic acid oxidase: enzyme replacement therapy for alkaptonuria; Gene therapy hope for ochronosis patients; Cartilage and bone biomarkers, including preliminary results in alkaptonuria; and more.
For further details

International Ataxia Research Conference
Date: 1-3 November 2012
Venue: London, UK

Topics will include emerging therapeutic strategies for the ataxias; genetic and molecular analysis of the frataxin gene and protein; episodic ataxias and non-inherited ataxias; ataxia clinical research from trials to clinic – biomarkers and clinical trials; and more.
For further details

8th International Society for Newborn Screening European Regional Meeting
Date: 4-6 November 2012
Venue: Budapest, Hungary

Topics will include: To screen or not to screen - setting up screening panels; Congenital adrenal hyperplasia; Cystic fibrosis; Severe combined immune deficiencies; Lysosomal storage disorders; and more. .
For further details

6th International Symposium on Childhood MDS and Bone Marrow Failure syndromes
Date: 7-9 November 2012
Venue: Prague, Czech Republic

Topics will include Refractory Cytopenia of Childhood, advanced MDS; Juvenile Myelomonocytic Leukemia; Ph-negative Myeloproliferative Disorders; Therapy-related myeloid neoplasia; Severe Aplastic Anemia; Congenital Bone Marrow Failure; Morphology and Classification; Stem cell biology; Molecular aberrations and potential targets; Novel therapeutics, and Hematopoietic Stem Cell Transplantation.
For further details

3rd Annual World Orphan Drug Congress
29-30 November 2012
Geneva, Switzerland

The 3rd annual World Orphan Drug Congress provides a forum for the rare disease industry. This commercial event has three dedicated tracks this year: clinical development and R&D; market access, pricing, and reimbursement; corporate development and partnerships.
For further details

Translating Genomics Conference
Date: 4 December 2012
Venue: Cambridge, UK

Topics include: Using genomics to improve population health; Non-invasive prenatal diagnosis using fetal DNA in maternal plasma: from dream to reality; The public health perspective on translating genomics into health benefits: more important than ever; and more.
For further details

10th Asia-Pacific Conference on Human Genetics
Date: 5-8 December 2012
Venue: Kuala Lumpur, Malaysia

The APCHG2012 will examine various themes on personalised medicine, human variations in the Asia-Pacific region as well the latest advances on genetic diagnostics and technology and their implications to healthcare in the region. In addition, the APCHG2012 will also discuss issues pertaining to bioethics, genetics education and counselling as well as preventative strategies for birth defects and inborn errors of metabolism, and to provide a platform for patients and families to discuss emerging issues in individuals with inherited conditions and chronic disabilities.
For further details

Symposium ATP1A3 in Disease: From Gene Mutations to New Treatments
Date: 10-11 December 2012
Venue: Brussels, Belgium

The Symposium follows up on the recent breakthrough research on Alternating Hemiplegia of Childhood and Rapid-onset Dystonia Parkinsonism. It aims to facilitate further studies and collaborations and is intended for researchers, physicians, health professionals, private and public companies, and patient associations.
For further details

3rd Annual World Orphan Drug Congress
Date: 9-11 April 2013
Venue: Washington DC, USA

This event brings together industry, patient groups, payers and government seeking to expedite orphan drugs to patients.
For further details

First GENCODYS International Conference: Integrative Networks in Intellectual Disabilities
Date: 14-17 April 2013
Venue: Paphos, Cyprus

Proposed topics include: Cognitive disorders (CD): Phenotype-Genotype networks; gene identification, gene networks-complex inheritance; Linking CD genes and behavioural traits to neural networks; Disease mechanisms in CD – the synapse, gene regulation, epigenetic conditions, common pathways; therapeutic intervention.
For further details

7th Alstrom Syndrome International Family Conference and Scientific Symposium
Date: 9-13 May 2013
Venue: Massachusetts, USA

Medical professionals and scientists will hold Symposia on Thursday, 9 May and Saturday 11 May.
For further details

Autoinflammation 2013: 7th International Congress of the International Society of Systemic Auto-Inflammatory Diseases
Date: 22- 26 May 2013
Venue: Lausanne, Switzerland

The meeting will offer a unique opportunity to gather experts from all over the world to discuss the latest scientific and clinical issues on different topics, including the challenges of the new treatments for autoinflammatory diseases such as familial Mediterranean fever; new monogenic autoinflammatory diseases; systemic-onset JIA; Behçet; granulomatous diseases; amyloidosis; and other conditions.
For further details

9th European Cytogenetics Conference
Date: 29 June - 02 July 2013
Venue: Dublin, Ireland

An opportunity for cytogeneticists to come together to discuss developments ranging from applications in prenatal or cancer diagnosis to chromosome biology in epigenetics and evolution.
For further details

8th International Prader-Willi Syndrome Conference
Date: 17-21 July 2013
Venue: Cambridge, UK

An opportunity for all involved worldwide in research, working or living with people with PWS to present current research and explore best practice in clinical and day to day management of PWS.
For further details

First International Primary Immunodeficiencies Congress (IPIC)
Date: 7-8 November 2013
Venue: Estoril, Portugal
The International Patient Organisation for Primary Immunodeficiencies (IPOPI) announces the First International Primary Immunodeficiencies Congress (IPIC), a congress for all stakeholders with an interest in primary immunodeficiencies (PIDs). IPIC will provide a two-day programme focusing on clinical developments including PIDs pathogenesis, treatment, management of complications and more. Access to diagnosis and care, SCID newborn screening and other key world developments will also be addressed.
For further details


Media, Press & Publications

Three new German-language articles consider off-label drug use
Off-label use of medicinal products is a critical issue for rare diseases, due to the lack of specifically approved treatments. Three German-language articles have recently been published that consider legal and related issues around off-label medication usage.
Consult the PubMed abstracts


Orphanews Europe, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews Europe 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: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Helena Kaariainen, Odile Kremp, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Jaroslaw Waligora

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

Orphanet Partner Country Representatives: Tamara F. Sarkisian (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), Manfred Stuhrmann-Spangenberg (Germany), Helen Michelakakis (Greece), Sandor Janos (Hungary), Andrew Green (Ireland), Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Viadutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
For more information on the European Union Committee of Experts on Rare Diseases
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