2 August 2013 print
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Report on the public consultation on the implementation of European Reference Network
The development of the European Reference Networks and of the Centres of Excellence will greatly facilitate access to diagnosis and delivery of high-quality and cost-effective healthcare especially, but not entirely, for patients suffering from rare diseases. Article 12 of the Directive on the application of patients' rights in cross-border healthcare, requires the Commission to adopt a list of criteria that the networks must satisfy, and the conditions and criteria, which providers wishing to join networks must meet. In addition, they have to develop and publish criteria required to establish and appraise European Reference Networks. Furthermore, the Commission must also facilitate the exchange of information and expertise on these.

In order to accomplish the goals of Article 12, DG Health & Consumers initiated a public consultation targeted to stakeholders on the implementation of European Reference Networks (ERN) and in particular on the criteria to be considered accordingly. The objective of the public consultation was to consult stakeholders to receive input of interested parties as to how the criteria for the scope and for European Reference Networks and the healthcare providers wishing to join the network could be addressed and facilitated.

A summary and all contributions received from stakeholders regarding the above mentioned public consultation is now published in a report entitled “Public consultation on the implementation of European Reference Networks (ERN)”. This document summarises the contributions made by stakeholders on the elements to be addressed in the implementation of Article 12 of the Directive 2011/24/EU on European Reference Networks (ERN), and in particular on the criteria to be considered in the process of identification and designation of healthcare providers as Centres of Expertise.

Based on 138 respondents from stakeholders across Europe, the respondents mostly agreed on the majority of the criteria set out by the Commission. Additional opinions of the respondents on changes or addition of criteria is also available in the Annex section of the document.
Go to the DG SANCO website
Read the EUCERD recommendations on European Reference Networks


EUCERD update
EUCERD adopts opinion on Potential Areas of European Collaboration in the Field of New Born Screening

In July 2013, the EUCERD adopted a document entitled New Born Screening in Europe: Opinion of the EUCERD on Potential Areas for European Collaboration. In the Council Recommendation of 8 June 2009 on an action in the field of rare diseases, it is recommended that Member States “Gather national expertise on rare diseases and support the pooling of that expertise with European counterparts in order to support: the development of European guidelines on diagnostic tests or population screening, while respecting national decisions and competences”.

The EUCERD was requested by the European Commission to examine the outputs of the tender within the EU Program of Community Action in Public Health (work plan 2009) for an “Evaluation of population newborn screening practices for rare disorders in Member States of the European Union” (read the Executive Report here) and to issue their proposals for next steps.

As a result of their discussions in this area, the EUCERD has agreed on 11 areas which respect the principle of subsidiarity, including actions to improve the quality and the efficiency of the screening process, while respecting the values of the Member States. These areas are not prioritised and are are submitted to the European Member States, to the European Commission and to any third party involved for further consideration.

The European Commission has also been provided with a full report of the discussions of the EUCERD meeting including individual Member States and stakeholders' opinions on the possible prioritisation of these 11 areas for their information. Read the opinion here

EU Policy News
European Commission publishes report on the first five years of the EU Paediatric Regulation
The European Commission has delivered its general report on result of the application of Regulation (EC) No 1901/2006 on medicinal products for paediatric use to the European Parliament and the Council. The report entitled 'better medicines for children – from concept to reality’ has acknowledged the efforts of the EMA and EU. The report also highlights the new indications and new medicines authorised for children, as well as the successes of the Paediatric Regulation after five years, recently published by the Agency. The report features successes in the past five years and the marked increase in the number of neonates included in clinical trials, the cooperation with other international authorities such as the United States Food and Drug Administration to allow global product development. The report also emphasises that the significant number of deferrals granted ascertaining that the Commission and the Agency expects an even greater number of new medicines and indications for children in the next few years. Although there has been significant progress in the field of paediatric medicinal product development, the report also highlight some areas for improvement.


National & International Policy Developments
Guidance Documents and Recommendations
Fragile X syndrome: American College of Medical Genetics and Genomics (ACMG) standards and guidelines for testing
Consult the Pubmed abstract
To read more about "Fragile X syndrome"
To read more about "Fragile X-associated tremor/ataxia syndrome"

Genet Med. ; 15(7):575-86 ; July 2013
Bioinformatics, Registries and Data Management
Development of a novel predictive algorithm to assertain phenotypic severity in mucopolysaccharidosis type I patients
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem lysosomal storage disease caused by deficiency of the enzyme α-L-iduronidase (IDUA). Patients suffering from MPS present with a continuous spectrum of disease severity, and the most severely affected patients (Hurler phenotype; MPS I-H) develop progressive cognitive impairment. The treatment of choice for MPS I-H patients is haematopoietic stem cell transplantation (HSCT), while patients with the more attenuated phenotypes benefit from enzyme replacement therapy (ERT). The potential of newborn screening (NBS) for MPS I is currently studied in many countries as early assessment of the phenotype is crucial in order to decide on the appropriate treatment. In a study published in Orphanet Journal of Rare Diseases, the authors have developed an algorithm to predict phenotypic severity in newborn MPS I patients.

Genotypes of 30 patients were collected and they were phenotypically categorized at an age of > 18 months based on the clinical course of the disease. Using genetic, biochemical and clinical characteristics, all of which are potentially available during the neonatal period, the authors developed an algorithm that "predicts the MPS I phenotype, allowing timely initiation of the optimal treatment strategy after introduction of NBS, thus improving disease outcome".

According to the authors, the algorithm described in this study can be used for “early determination of phenotypic severity in patients with MPS I diagnosed through NBS, combining mutational analysis, determination of residual enzyme activity in cultured skin fibroblasts and clinical characteristics that are apparent within the first month of life”. This algorithm may also allow separation of those MPS I patients who will benefit from HSCT at an early age from those that will optimally benefit from an early start of ERT.
Read the open access article

The DYSCERNE pilot project report
An article in European Journal of Human Genetics has reported the outcome of the DYSCERNE pilot project. This project was funded by the European Commission Public Health Executive Agency (EU DG Sanco) in 2007, to set up a network of expertise for patients with rare dysmorphic disorders. As part of DYSCERNE, a Dysmorphology Diagnostic System (DDS) was set up to enable clinicians throughout the EU to submit cases electronically for diagnosis using a secure, web-based interface, hosted at specified access points, in 26 different European countries. The aim was to facilitate diagnosis of rare syndromes associated with physical, growth and developmental problems.

The article reports on the 200 cases submitted –each of which was reviewed by an average of 5 experts- between January 2010 and 2012. According to the authors, while 70.5% were referred to genetic testing and other laboratory investigations and diagnostic imaging were recommended for 35.5 and 26% of the cases, respectively. Furthermore, specialized opinions were suggested in 23.5% of the cases and out of the lot 22.5% received a clinical diagnosis. Overall, a total of 181 very rare or extremely rare genetic syndromes were considered in the differential diagnosis of the 200 cases.

The authors believe that platforms like DDS is essential as Next-Generation Sequencing is not widely available yet but they assert that "as these technologies become available the clinical geneticist will shift to the clinical management of these patients that can be facilitated by systems such as the DDS".
Consult the PubMed abstract

Screening and Testing
Next-generation sequencing: a tool for diagnosing rare autosomal recessive neurologic Mendelian disorders
A study published in Neurobiology of Aging describes how Next-generation sequencing (NGS) was used to investigate nine rare Chinese pedigrees with rare autosomal recessive neurologic Mendelian disorders. In this article the authors have demonstrated the advantages of using next-generation sequencing to diagnose rare autosomal recessive neurologic Mendelian disorders characterized by genetic and phenotypic heterogeneity. The authors identified a list of known and novel candidate variants for each causative gene, they were “genetically verified by Sanger sequencing or quantitative polymerase chain reaction with the strategy of disease segregation in related pedigrees and healthy controls”.

Based on the results of their study, the authors propose that a genetic diagnostic strategy relying on NGS can provide new insights into neurologic Mendelian disorders. They believe that if a "definitive diagnosis is difficult to determine for diseases with genetic and phenotypic heterogeneity, the use of whole genome sequencing (WES) can provide a convenient approach to confirm known causative variations or discover novel candidate mutations, thus making a genetic diagnosis or supporting disease-risk counselling".

The authors believe that combined strategy of using targeted gene sequencing (TGS) and WES on NGS platforms has shown great promise for improving the diagnosis of neurologic Mendelian disorders. Additionally, the authors also assert that "NGS could become a routine clinical evaluation tool for most autosomal recessive neurologic Mendelian disorders with up-to-date improvements on sequencing technology and the analytical approach".
Consult the PubMed abstract

Report of the International Workshop on Newborn Screening for Duchenne Muscular Dystrophy
The 195th ENMC International Workshop on newborn screening (NBS) for Duchenne muscular dystrophy (DMD) was held in Naarden, The Netherlands, on 14–16th December 2012. A report detailing the proceeds of this meeting is published in Neuromuscular Disorders. The average global DMD incidence is now closer to 1:5000 but immediate pharmacological interventions do not currently exist for infants with DMD. The lack of available treatment is viewed by NBS programme regulators worldwide as a significant obstacle to add DMD to the national screening programmes. This report emphasises that any delay in the diagnostic process will have resulted in late genetic counselling and possibly the birth of a second DMD child. The report maintains that although the diagnosis of DMD is never welcome, hearing it sooner rather than later allows for the appropriate planning of the needed financial, reproductive and social support.

The report underscores the encouraging aspects such as current drug trials for the treatment of DMD which are underway. The report cautioned that while results from ongoing experimental studies using drugs that induce exon skipping and read-through stop codons appear promising, and the outcome of confirmatory phase 3 studies will be available during the course of 2013, at the moment there is no immediate intervention in the neonatal period that directly benefits the affected DMD children.

However, in light of these drug developments, the report encourages being ready with screening programmes in the event of a satisfactory treatment being available for DMD in the near future. To be prepared for this eventuality, the report stresses the need to strengthen efforts in developing a Standard Operating Procedure for a screening assay, distribute it to other screening sites across the globe, so as to assess its screening efficacy on more children and across populations.
Consult the PubMed abstract

Non-Invasive Prenatal Testing of Fetal Aneuploidies by Massively Parallel Sequencing
A study published in Prenatal Diagnosis evaluated the performance of NIPT for detection of foetal aneuploidies in Chinese women younger than 35 years of age. They sequenced maternal plasma samples to identify the aneuploidies. The results of the sequencing was then compared against the serum screening results, and validated by karyotyping through invasive procedures and birth follow-up. They found that non-invasive prenatal detection of common foetal aneuploidies "is a more sensitive and specific method than triple maternal serum screening". The authors highlight that “this method has a remarkable low false positive rate and is applicable to women younger than 35 years old”.
Consult the PubMed abstract


Ethical, Legal & Social Issues
The saga of the transparency directive
The Guardian has published an article on the leaked email from the director of European Federation of Pharmaceutical Industries and Associations (EFPIA), asking the pharmaceutical industry to mobilise patient groups to fight the transparency directive. This has caused concern from various sectors. According to The Guardian, the email included a memo from Richard Bergström, director general of EFPIA, was addressed to “directors and legal counsel at Roche, Merck, Pfizer, GSK, AstraZeneca, Eli Lilly, Novartis and many smaller companies (and) leaked by a drug company employee”. Although the email has not been published, the Guardian claims that the content reflects a campaign to resist sharing data more freely. Accorting to The Guardian the email starts with "mobilising patient groups to express concern about the risk to public health by non-scientific re-use of data" and goes on to explain a “four pronged approach to resist data sharing".

In keeping with Regulation (EC)1049/2001, the European Medicines Agency aimed to increase transparency by providing access to institution documents to the public on request. However, two pharmaceuticals companies, AbbVie and InterMune, contested the release of certain documents provided by them to the EMA at the general court of the European Union. The general court of the European Union provided an interim judgement in favour of AbbVie and InterMune and has prohibited the EMA from releasing the concerned documents before the delivery of the final judgement. This has been a major setback, however, the EMA has tried to move ahead to try and work with the pharmaceutical companies by providing a draft guideline on the release of documents, which is now open for public consultation. However, industry groups are opposed to the plan of the European Medicines Agency, which oversees approvals in Europe, to make trial data public whenever a drug is approved.

In related news, EFPIA and Pharmaceutical Research and Manufacturers of America (PhRMA) have released a statement pledging to release detailed data about their drugs to outside researchers. Released days after The Guardians’ article, this proposal will take effect on 1 January 2014. It would apply to all new drugs and all new uses for existing drugs, whether approved in the United States or the European Union. This proposal has unanimous approval from the EFPIA and PhRMA member companies.
Read the Press Statement by EFPIA and PhRMA

Chronic diseases patients receive respite in cost sharing in France, Germany, Japan, the UK and the US
Many countries that belong to the Organisation for Economic Co-operation and Development (OECD) forum created or expanded cost sharing programs to reduce the demand for health care services between 2000 and 2010. In an article published in Health Policy, the authors focus on changes in cost sharing in three divisions of the healthcare industry — pharmaceutical, outpatient and inpatient services — during this period. The authors obtained data on three different types of cost sharing: deductibles, co-insurance and co-payments and compared the measures taken to protect vulnerable groups in France, Germany, Japan, the UK, and the US. The authors believe that this article provides vital information where "countries can learn from the experiences of other countries while still maintaining their own unique healthcare systems".

Cost sharing in pharmaceutical expenses increased in all countries to a varying significantly in these five countries - the highest on per capita out-of-pocket in the U.S. to the lowest in France - in 2010. The authors showed that France protected patients with 30 chronic conditions from this increased cost sharing by including “100% reimbursement for non-substitutable or expensive prescription drugs and a cap on annual out-of-pocket payments at Euros 50”. Several regulations were designed to protect individuals with chronic diseases in Germany where people who have chronic conditions have to pay only 1% of the gross annual household income. In Japan, no provisions are made for chronic conditions or rare diseases, while UK has provisions to protect all chronic or long term conditions. In the US the authors examined patients on Medicare and it noted that most Medicare recipients purchase Medigap, so although chronic care patients received significant reimbursements it is never 100%.

The authors also note that in France people with 30 specific long-term illnesses as well as other rare diseases that are not listed in the 30 disease list are excluded from cost sharing for hospital services. In Germany, patients who have a serious chronic disease have to pay only 1% of their gross household income. Japan excludes patients from cost sharing if they have one of 56 chronic diseases. While in UK almost all of the covered inpatient health services operate without cost sharing. In US there is no provision specific to rare disease patients but the federal government has many different programs for protecting beneficiaries.

Chronic disease patients are mostly exempted from cost sharing for the provision of ambulatory care in all these countries.
Consult the PubMed abstract

Non-invasive prenatal diagnosis from the perspective of a low-resource country
The rapid spread of prenatal diagnosis based on cell-free fetal DNA in high-income countries, brings to question how this cutting-edge technology might influence current practice of obstetrics in low-resource countries. The article published in Prenatal Testing gives an overview of how prenatal diagnosis is currently being offered in high-income countries and argue that people from low-resource countries also require access to prenatal diagnosis. They stress that implementation of prenatal diagnosis—both invasive and non-invasive—on a systematic and equitable basis in low-income countries is required as congenital disorders have largely been neglected as a health problem in these regions.

However, according to the authors, many of these countries are undergoing an epidemiologic transition, and hence congenital disorders are now contributing significantly to perinatal morbidity and mortality. Additionally, the authors argue that even when abortion is not an option for women from many low-income countries, prenatal diagnosis is invaluable because most women will be reassured when the results are favourable. Conversely, when an abnormality is found, they will have more time to prepare themselves for the adverse situation, wherein a diagnosis of a foetal condition might help healthcare workers to plan the birth and to refer the pregnant woman to a proper tertiary center. The authors emphasise that there is no reason to offer an invasive test with subsequent risk of miscarriage when there is the option of a non-invasive prenatal diagnosis (NIPD) with no risk. They contend that withholding this current option from pregnant women during counselling is unethical even for low-income families.

The authors highlight the main limitations in introducing NIPD into low-resource countries which include availability, financial ability, trained personnel providing the test and prenatal genetic counselling as well as the cultural beliefs among patients and healthcare providers. However, the authors firmly believe that commitment from health policy-makers and healthcare providers and general public NIPT can be reality in poorer countries.
Consult the PubMed abstract


Orphanet News
New Research Projects open for Recruitment
Clinical trial for Sebelipase alfa (enzyme replacement therapy) for the treatment Lysosomal Acid Lipase Deficiency: open for recruitment
Lysosomal Acid Lipase (LAL) Deficiency is a progressive disease with multi-systemic clinical manifestations, significant medical complications and early mortality. The clinical signs and symptoms may correlate with a patient’s residual levels of endogenous LAL.

Sebelipase alfa, a recombinant human LAL enzyme, has been identified as an investigational enzyme replacement therapy (ERT). This drug, developed by Synageva Biopharma, is designed to replace the functionality of the deficient LAL enzyme, which is responsible for the metabolism of cholesteryl esters and triglycerides that are delivered to lysosomes by a variety of routes including LDL receptor mediated endocytosis. Sebelipase alfa has received orphan drug designations in EU and a ‘Breakthrough Therapy Designation’ from the FDA for the treatment of infants with early onset growth failure due to LAL Deficiency.

A Multicenter, Randomized, Placebo-Controlled Study of sebelipase alfa in Patients with Lysosomal Acid Lipase Deficiency in both adults and children with the late onset phenotype of LAL deficiency is now enrolling patients. This Phase 3 ‘ARISE' (Acid Lipase Replacement Investigating Safety and Efficacy) Study seeks to assess the efficacy, safety, and tolerability of sebelipase alfa in 50 patients at global study sites. If you wish to enroll in the trial please contact Synageva Biopharma Learn more about the ARISE study


New Syndromes

A novel autosomal recessive intellectual disability syndrome caused by GPI anchor deficiency due to homozygous mutations in PIGT

A novel autosomal recessive syndrome, characterised by distinct facial features, intellectual disability, hypotonia and seizures, in combination with abnormal skeletal, endocrine, and ophthalmologic findings was found in four patients from a consanguineous kindred. This syndrome is caused by GPI anchor deficiency due to homozygous mutations in PIGT.
Consult the Pubmed abstract
J Med Genet. ; 50(8):521-8 ; August 2013
New subtype of spinocerebellar ataxia with altered vertical eye movements linked to chromosome 1p32

The authors reported a new subtype of spinocerebellar ataxia with altered vertical eye movements linked to an 11-megabase interval on 1p32 in a Spanish kindred. For most patients, the initial symptoms included falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. Neuroimaging showed isolated cerebellar atrophy.
Consult the Pubmed abstract
JAMA Neurol. ; 70(6):764-71 ; June 2013
New syndrome of infantile neuroaxonal dystrophy with facial dysmorphism due to a recessive truncating NALCN mutation

A new syndrome of infantile neuroaxonal dystrophy including facial dysmorphism, pectus carinatum, scoliosis, pes varus, zygodactyly, and bilateral cryptorchidism as well as cerebellar atrophy was reported. A homozygous truncating mutation in NALCN was identified as responsible for this new syndrome.
Consult the Pubmed abstract
J Med Genet. ; 50(8):515-20 ; August 2013

New Genes

Congenital fiber-type disproportion with left ventricular non-compaction myopathy due to digenic mutations in MYH7B and ITGA7
Consult the Pubmed abstract
To read more about "Left ventricular noncompaction"
To read more about "Congenital fiber-type disproportion myopathy"

Orphanet J Rare Dis. ; 8:91 ; June 2013
Autosomal recessive intermediate Charcot-Marie-Tooth disease: identification of novel compounds heterozygous mutations in PLEKHG5 gene
Consult the Pubmed abstract
To read more about "Charcot-Marie-Tooth disease"
To read more about "Autosomal recessive intermediate Charcot-Marie-Tooth disease"

Orphanet J Rare Dis. ; 8(1):104 ; July 2013
Microphthalmia with limb anomalies-like condition: whole-exome sequencing identified a homozygous FNBP4 pathogenic mutation in a Lebanese family
Consult the Pubmed abstract
To read more about "Microphthalmia with limb anomalies"

Am J Med Genet A. ; 161(7):1543-6 ; July 2013
Childhood onset idiopathic and/or familial pulmonary arterial hypertension associated with TBX4 mutations or TBX4-containing deletions
Consult the Pubmed abstract
To read more about "Idiopathic and/or familial pulmonary arterial hypertension"
To read more about "Coxo-podo-patellar syndrome"

J Med Genet. ; 50(8):500-6 ; August 2013
Oculocerebrofacial syndrome, Kaufman type caused by UBE3B loss of function
Consult the Pubmed abstract
To read more about "Oculocerebrofacial syndrome, Kaufman type"

J Med Genet. ; 50(8):493-9 ; August 2013
Brugada syndrome: a missense mutation in the sodium channel β2 subunit reveals SCN2B as a new candidate gene
Consult the Pubmed abstract
To read more about "Brugada syndrome"

Hum Mutat. ; 34(7):961-6 ; July 2013

Research in Action

Clinical Research
POEMS syndrome: long-term outcomes of patients treated with radiation
Consult the Pubmed abstract
To read more about "POEMS syndrome"

Blood. ; 122(1):68-73 ; July 2013
Glioblastoma: review on advances in immunotherapeutic strategies
Consult the Pubmed abstract
To read more about "Glioblastoma"
To read more about "Glial tumor"

Mol Ther. ; 21(7):1297-305 ; July 2013
Systemic sclerosis: high incidence of hypothyroidism and thyroid dysfunction in female sclerodermic patients
Consult the Pubmed abstract
To read more about "Systemic sclerosis"

J Clin Endocrinol Metab. ; 98(7):E1198-202 ; July 2013
Facioscapulohumeral dystrophy: FAT1 may act as a novel disease modifier
Consult the Pubmed abstract
To read more about "Facioscapulohumeral dystrophy"

PLoS Genet. ; 9(6):e1003550 ; June 2013
Gene Therapy
Fukuyama and related dystroglycanopathies: AAV-mediated rescue of fukutin expression limited in myofibers successfully ameliorated severe pathology in mice
Consult the Pubmed abstract
To read more about "Congenital muscular dystrophy, Fukuyama type"

Hum Mol Genet. ; 22(15):3003-15 ; August 2013
Therapeutic Approaches

Ebola hemorrhagic fever: FDA approved selective estrogen receptor modulators inhibit infection in mice
Consult the Pubmed abstract
To read more about "Ebola hemorrhagic fever"

Sci Transl Med. ; 5(190):190ra79 ; June 2013
Chronic autoimmune hepatitis: splenectomy prolongs the effects of corticosteroids in mouse models
Consult the Pubmed abstract
To read more about "Chronic autoimmune hepatitis"

Gastroenterology ; 145(1):209-220.e9 ; July 2013
Pancreatic carcinoma: targeted therapy by polymeric micelles prolongs survival and prevents peritoneal metastasis in model mice mimicking human disease
Consult the Pubmed abstract
To read more about "Pancreatic carcinoma"

Proc Natl Acad Sci U S A ; 110(28):11397-402 ; July 2013
Diagnostic Approaches

Rare dystonia: review on the mechanistic insights provided by the study of the genetic causes, and clinical algorithm to aid in correctly predicting the genetic basis
Consult the Pubmed abstract
To read more about "Rare dystonia"

Brain ; 136(Pt 7):2017-37 ; July 2013
Rendu-Osler-Weber disease: infrared spectroscopy and artificial neural network as a serious alternative diagnostic method compared to clinical and genetically based methods
Consult the Pubmed abstract
To read more about "Rendu-Osler-Weber disease"

Orphanet J Rare Dis. ; 8:94 ; June 2013

Patient Management and Therapy
Aggressive mature natural killer cell neoplasms: review on epidemiology and diagnosis
Consult the Pubmed abstract
Orphanet J Rare Dis. ; 8:95 ; July 2013
Glycogen storage disease due to acid maltase deficiency: review on pharmacotherapy
Consult the abstract
To read more about "Glycogen storage disease due to acid maltase deficiency"

Expert Opinion on Orphan Drugs ; 1(6):6457-471 ; June 2013
Short bowel syndrome: two reviews on characterisation and non-surgical treatment in adult patients
Consult the abstracts
To read more about "Short bowel syndrome"

Expert Opinion on Orphan Drugs ; 1(7): 515-525, 527-538 ; July 2013
Myelofibrosis: growing role of immunomodulatory agents such as pomalidomide
Consult the abstract
To read more about "Myelofibrosis with myeloid metaplasia"
To read more about "Essential thrombocythemia"
To read more about "Polycythemia vera"

Cystic fibrosis: summary of the epidemiology, genetics and pathogenesis, emphasizing aerosolized levofloxacin therapy
Consult the abstract
To read more about "Cystic fibrosis"

Expert Opinion on Orphan Drugs ; 1(7): 549-556 ; July 2013
Congenital myotonia: prospective study of objective and patient reported outcomes
Consult the Pubmed abstract
To read more about "Thomsen and Becker disease"
To read more about "Paramyotonia congenita of Von Eulenburg"
To read more about "Hyperkalemic periodic paralysis"
To read more about "Potassium-aggravated myotonia"

Brain ; 136(Pt 7):2189-200 ; July 2013

Orphan Drugs
Regulatory News
22 positive opinions recommending orphan designation at the June 2013 COMP meeting
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted twenty two positive opinions issued at the June 2013 COMP meeting for the treatment of:

- pulmonary alveolar proteinosis
- B-lymphoblastic leukaemia/lymphoma
- pancreatic cancer
- malignant thymomas
- plasma cell myeloma
- ataxia telangiectasia
- limbal stem cell deficiency
- ovarian cancer
- hyperargininaemia
- carbamoylphosphate synthase-1 deficiency
- ornithine translocase deficiency (hyperornithinaemia-hyperammonaemia homocitrullinuria (HHH) syndrome)
- citrullinaemia type 2
- argininosuccinic aciduria
- citrullinaemia type 1
- N-acetylglutamate synthetase (NAGS) deficiency
- prevention of ischaemia/reperfusion injury associated with solid organ transplantation
- lymphoplasmacytic lymphoma
- prevention of hepatitis B re-infection following liver transplantation
- 2 treatments for amyotrophic lateral sclerosis
- 2 treatments for follicular lymphoma

Breakthrough Therapy Designation to Asfotase Alfa for Perinatal-, Infantile- and Juvenile-Onset Hypophosphatasia (HPP)

Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to asfotase alfa for the treatment of patients with hypophosphatasia (HPP) whose first signs or symptoms occurred prior to 18 years of age, including perinatal-, infantile-, and juvenile-onset forms of the disease. HPP is an inherited, life-threatening, ultra-rare metabolic disorder that leads to progressive damage to multiple vital organs, including destruction and deformity of bones. The FDA also confirmed that adult-onset HPP is "a serious and life threatening disease or condition" and that Breakthrough Therapy designation could be obtained for this aspect of the disease with additional clinical information.
For further details

Political and Scientific News
Orphan and non-orphan drugs treated the same: study shows that both go through similar stringent reviews for marketing authorisation in EU
An article in Drug Discovery Today demonstrates the existence of strong similarity in the way orphan and non-orphan drugs are reviewed and assessed in the European regulatory marketing authorization system. The authors compared marketing authorization applications of 17 orphan drugs (ODs) and 51 non-ODs evaluated by the European Medicines Agency (EMA) in the period 2009–2010. They specifically attempted to identify differences between ODs and non-ODs in number and type of deficits brought forward during the EMA review, regarding the clinical development plan, clinical outcome and medical need and studied whether these deficits were similarly associated with marketing approval in the EU.

The authors found differences in deficits, but also found similarities in the way ODs and non-ODs were reviewed and marketing approval decisions were taken, underlining the equally high regulatory standards between the two. The authors established that in the majority of licensed ODs, approval was based on robust randomized clinical trials and endpoints that were considered clinically relevant. The authors found differences between ODs and non-ODs in the area of "study design (i.e. use of single arm studies), clinically relevant endpoint (i.e. more challenging for ODs), finding the appropriate target population (i.e. for ODs less a challenge than for non-ODs), safety profile (i.e. for most ODs less favourable), acknowledged high medical need (i.e. in two third of ODs dossiers, one fifth of the non-ODs dossiers)". They argued that these differences are due to the limitations inherent to studying rare diseases as original OD submissions are based on smaller studies but the EMA’s identified and weighted deficits (i.e. concerns, doubts and objections) rather than the study design characteristics.

This study shows that the EMA did not accept lower levels of evidence (development and outcome) for ODs and non-ODs, unless this could be well justified by the applicant, when limited opportunities for further research allowed exceptional approval or when the company committed to add additional data to meet the standards of drug development that EMA requires, and the OD was conditionally approved.
Consult the PubMed abstract



Jérôme Lejeune Foundation - Research Projects
The foundation will support projects of basic or clinical research (neuroscience, behavior, genetics, molecular biology, therapy, etc.) that is intended to result in the discovery of treatments to improve the capacity of patients with genetic diseases with intellectual disabilities, especially the Trisomy 21 (except autism). Projects oriented towards clinical studies will be given priority. Application deadline is: 19 August 2013. For further information email conseilscientifique@fondationlejeune.org
Consult the website

NORD announces seed grants for rare disease research
NORD has announced funding opportunities in 6 areas of rare disease research. NORD has invited applicants from within the US and overseas to apply. Full proposals are due by 11 September 2013. Researchers with projects in the following areas are encouraged to apply

RFPs for Pseudomyxoma Peritonei (PMP), Spring 2013
Two grants are available through NORD ($50,000/grant) for research related to Pseudomyxoma Peritonei (PMP).

RFP for Growth Failure in Children with Cardiofaciocutanous (CFC) Syndrome
Funding is available ($30,000) for research on growth failure in children with cardiofaciocutaneous (CFC) syndrome.

RFP for Glycine Encephalopathy, aka Nonketotic Hyperglycinemia, Spring 2013
Funding for research related to Glycine Encephalopathy, aka Nonketotic Hyperglyinemia, is available through NORD's Research Seed Grant Program ($34,000).

RFP for Adult Primary Lateral Sclerosis (PLS)
Funding is available ($30,000) for research on Primary Lateral Sclerosis (PLS).

RFP Available for Research Related to Dubowitz Syndrome
Funding is available ($30,000) for research on Dubowitz Syndrome
For further details

DEBRA International research grants
The autumn 2013 call for applications for new research funding from DEBRA International is now open, with a submission deadline of 15 September 2013. DEBRA International welcomes proposals for co-funding with other organisations, including government, academia, industry or other charities. DEBRA will not, however, fund generic technology development costs not closely related to a specific EB therapeutic approach.
For Further Details


Partnersearch, Job Opportunities
Grantholder position for the establishment of the European Technological Platform on Rare Diseases
The JRC Institute for Health and Consumer Protection has started recruitment for the Grantholder position for establishing the European Technological Platform on Rare Diseases. The tasks will involve liaising with the Rare Diseases expert communities and patient organisation. Candidates with extensive experience working in the field of RD and/or epidemiology are encouraged to apply: For further details

Courses & Educational Initiatives
The 1st World Conference on Congenital Disorders of Glycosylation
Date: 1-2 September 2013
Venue: Barcelona, Spain

This conference is included in the ICIEM program and it is coordinated by the Portuguese association for Congenital Disorders of Glycosylation (CDG) and related Rare Metabolic Diseases (APCDG-DMR). The conference will bring together patients with their families and the healthcare professionals who study the scientific and medical aspects of Congenital Disorders of Glycosylation (CDG), a growing family of rare metabolic disease. For further details

2nd International Workshop Rare disease and Orphan drug registries
Date: 21-22 September 2013
Venue: Rome, Italy

Application Deadline: 30 July 2013 Further Information about this course can be found on the epirare website For further details

International Summer School Rare Disease and orphan Drug Registries
Date: 16-20 September 2013
Venue: Rome, Italy

Application Deadline: 30 July 2013 Further Information about this course can be found on the epirare website For further details

Orphan Drug & Rare Disease Seminar: Accelerating access to therapeutic innovation
Date: 17-18 October 2013
Venue: Marseille, France

This event, jointly organised by Eudipharm, F-Crin and OrphanDev, will aim to address issues that to help fill the current discrepancies in translational research for rare diseases and creating awareness of clinical research sectors. For further details

European Cytogeneticists Association Courses
The European Advanced Postgraduate Course in Classical and Molecular Cytogenetics is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. Information for the 2014 course is now available. For Further details

What's on Where?

International Symposium on Urea Cycle Disorders (UCD)
Date: 1-2 September 2013
Venue: Barcelona, Spain

The symposium will focus on recent advances in UCD clinical and translational research which provide insights into the pathophysiology of these disorders. These advances will form the basis for the development of novel therapeutic approaches for UCDs that aim at decreasing mortality and preventing the effects of hyperammonemia on brain function. The satellite symposium will provide a forum for international researchers, clinicians, trainees and patients’ families to share and discuss research in UCD. This meeting will be the first formal joint meeting between the Urea Cycle Disorders Consortium (UCDC) and the European-Registry and Network for Intoxication Type Metabolic Disease (E-IMD).
For further details

International Congress of Inborn Errors of Metabolism
Date: 3-6 September 2013
Venue: Barcelona, Spain

The organisers have put together an ambitious and high level scientific programme, allowing the participation of multidisciplinary delegates where important topics and cutting edge research on inborn errors of metabolism will be discussed.
For further details

Orphan Drugs Summit 2013
Date: 11-13 September 2013
Venue: Copenhagen, Denmark

This commercial event will highlight several burning topics revolving market authorisation of Orphan Medicinal Products such as market access, regulatory framework, clinical trial development as well as financing.
For further details

2nd Conference of 'EB-CLINET - Clinical Network of EB Centres and Experts'
Date: 17-18 September 2013
Venue: Salzburg, Austria

The conference will present and discuss the work packages initiated during the 2012 EB clinet meeting.
For further details

16th International Conference on Behçet's Disease
Date: 18-20 September 2013
Venue: Paris, France

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

2nd International Symposium on Hypothalamic Hamartomas
Date: 20-21 September 2013
Venue: Marseille, France

This Symposium will provide a platform for collaboration and education and offer an opportunity to set a road-map for the next ten years of treatment and research for the treatment of hypothalamic hamartomas.
For further details

EUROPLAN National Conferences Finland
Date: 21 September 2013
Venue: Helsinki, Finland

Organised by Finnish Rare Diseases Alliance (HARSO)
For further details go to http://www.harsofinland.net

Second Symposium on ATP1A3 in disease Genotype/Phenotype Correlations, modelling and identification of potential targets for treatment
Date: 23 - 24 September 2013
Venue: Rome, Italy

The aim of this Symposium is to present the progress of research undertaken on Alternating Hemiplegia of Childhood (AHC), after the finding of the ATP1A3 gene as the primary cause of this rare neurological disease. The symposium also aims to promote international collaboration and recruit new teams of researchers. Clinical aspects of the disease such as genotype/phenotype correlations will also be highlighted as well as possibilities towards the establishment of clinical trials for AHC.
For further details

1st Iberoamerican Conference on Rare Diseases
Date: 24 - 25 September 2013
Venue: Brasilia, Brasil br>
This event will be held at University of Brasilia, Catholic University of Brasilia, where stakeholders of rare diseases nationally and internationally will be coming together to share their views.
For further details

EUROPLAN National Conferences Poland
Date: 27-28 September 2013
Venue: Krakow, Poland

Organised by Polish National Forum for rare diseases therapy (ORPHAN)
For further details visit www.rzadkiechoroby.pl/europlan

2nd International Expert Meeting on Congenital Melanocytic Nevi and Neurocutaneous Melanocytosis
Date: 28-30 September 2013
Venue: Marseille, France

This conference aims to report results and observations on Congenital Melanocytic Nevi and Neurocutaneous Melanocytic and paediatric melanoma as well as report to the medical and scientific community on the availability and development of patient-managed research resources. The conference also aims to incorporate various patient groups into a newly formed international federation.
For further details

Mitochondrial Disease: Translating biology into new treatments
Date: 2-4 October 2013
Venue: Cambridge, UK

This is a brand new conference that will discuss mitochondrial medicine. During this interactive conference several experts will speak about translational mitochondrial medicine. Abstracts are due by 16 July 2013 and the registration deadline is on 20 August 2013.
For further details

US Conference on Rare Diseases & Orphan Products: The New Era in Healthcare
Date: 7-9 October 2013
Venue: Maryland, United States of America

This annual meeting will be attended by stakeholders in the rare disease community - patients, patient organizations, researchers, drug and device companies, investors, thought leaders and government.
For further details

The 10th Balkan Congress of Human Genetics and 2nd Alps Adria Meeting on Human Genetics (AABC2013)
Date: 10-12 October 2013
Venue: Bled, Slovenia

This congress will deal with several issues pertaining rare genetic disorders, with sessions focusing exclusively on rare human disease.
For further details

Orphan Drugs and Rare Diseases
Date: 14-15 October 2013
Venue: London, UK

This commercial orphan drugs conference focuses on the current rare diseases drug development landscape where world leading expert speaking faculty will highlight cutting edge research via case studies taking place in previously untreatable patients with highly rare diseases, current regulatory policies involving the FDA & EMA, new drug discoveries and partnerships in clinical trials and drug development with patient groups.
For further details

Orphan Drug & Rare Disease Seminar “Accelerating access to therapeutic innovation”
Date: 17-18 October 2013
Venue: Marseille; France

This event, jointly organised by Eudipharm, F-Crin and OrphanDev, will aim to address issues that to help fill the current discrepancies in translational research for rare diseases and creating awareness of clinical research sectors.
For further details

3rd European Rett Syndrome Conference Maastricht, “Research Update & Preventive Management”
Date: 17-19 October 2013
Venue: Maastricht, The Netherlands

This conference aims to gather renowned researchers and clinicians working in the area of Rett Syndrome, to encourage interdisciplinary international cooperation. The conference also aims to provide stakeholders with the latest information on treatment of symptoms as well as preventative manangement.
For further details

Thalassemia International Federation World Congress
Date: 19-23 October 2013
Venue: Abu Dhabi, United Arab Emirates

Topics for this conference includes “all aspects of prevention, management and care of thalassemia and sickle cell disease and a one-day patient programme”.
For further details

The 2nd International Workshop Rare Disease and Orphan Drug Registries
Date: 21-22 October 2013
Venue: Rome, Italy

Application Deadline: 31 July 2013
For further details

World Cord Blood Congress IV and Innovative Therapies for Sickle Cell Disease
Date: 24-27 October 2013
Venue: Monaco, Principauté de Monaco

This international conference will cover a wide range of topics including cord blood transplant in adults and children, the role of HLA in cord blood transplant, stem cells, cord blood banking and regulatory issues. The scientific programme comprises of an international panel of distinguished scientitists and clinicians with a special session on sickle cell disease. This conference is open to all professionals working in fields related to cord blood biology and clinical applications from both public and private sectors, including physicians, research scientists, technicians, data analysts, nurses as well as healthcare policy makers.
For further details

EUROPLAN National Conferences Hungary
Date: 25-26 October 2013
Venue: Budapest, Hungary

Organised by HUFERDIS; Hungarian Federation of People with Rare and Congenital Diseases
For further details go to www.rirosz.hu

HGV2013: 14th International Meeting on Human Genome Variation and Complex Genome Analysis
Date: 30 September - 2 October, 2013
Venue: Seoul, South Korea
HGV2013 will bring together human geneticists from around the world to explore and share the latest in genetic technology, cancer genetics, population genetics, genomic medicine and more. This 3 day meeting will include plenary talks from over 25 high-profile speakers with over 200 posters, a student-mentor luncheon, a journal publishing workshop, and plenty of networking opportunities.
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

World Orphan Drug Congress 2013
Date: 14 November 2013
Venue: Geneva, Switzerland

This commercial conference and exhibition bringing together buyers, sellers and key influencers from across the orphan and rare disease industry. Having welcomed over 1000 orphan and rare disease stakeholders in only its 3 year history, the event in Europe’s logical choice for Biotech and Pharma orphan drug players who want to meet Rare Disease Networks, Patient Groups, COMP Members, HTA Experts, Regulators and Payers.
For Further Information

EUROPLAN National Conferences Lithuania
Date: 14 November 2013
Venue: Vilnius, Lithuania

Organised byMinistry of Health

EUROPLAN National Conferences Netherlands
Date: 14-15 November 2013
Venue: Netherlands

Organised by VSOP; the Dutch Genetic Alliance
For further details go to http://www.vsop.nl

EUROPLAN National Conferences Italy
Date: 15-16 November 2013
Venue: Rome, Italy


EUROPLAN National Conferences Luxembourg
Date: 19-20 November 2013
Venue: Luxembourg

Organised by Luxembourg Alliance for Rare Diseases and Neuro Muscular Diseases (ALAN)
For further details go to www.alan.lu/alan

EUROPLAN National Conferences Serbia
Date: 5-6 December 2013
Venue: Belgrade, Serbia

Organised by NORBS; Serbian National Organization for Rare Diseases
For further details go to www.norbs.rs>

EUROPLAN National Conferences France
Date: 13 January 2014
Venue: Paris, France

Organised by Alliance Maladies Rares
For further details go to www.alliance-maladies-rares.org

EUROPLAN National Conferences Spain
Date: 24 January 2014
Venue: Burgos, Spain

Organised by FEDER; the Spanish Alliance for Rare Diseases
For further details go to www.enfermedades-raras.org >

EUROPLAN National Conferences Ireland
Date: February 2014
Venue: Dublin, Ireland

Organised by GRDO, Genetic and Rare Disorders Organisation
For further details go to www.grdo.ie>

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

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

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

Batten disease is a common name for a group of rare, neurodegenerative genetic disorder affecting approximately 1 in 30,000 individuals. There is presently no known cure for Batten disease


Orphanews International, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews International is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Divya Unni
Editors for Scientific Content: Catherine Pouzat, Sophie Höhn
Contact Us
Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Barbara Cagniard, Virginie Hivert, Helena Kaariainen, Odile Kremp, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Jaroslaw Waligora

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

Orphanet Partner Country Representatives: Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Joerg Schmidtke (Germany), Helen Michelakakis (Greece), Zsuzsanna Lengyel (Hungary), Andrew Green (Ireland), Annick Raas-Rothschild (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Vaidutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
For more information on the European Union Committee of Experts on Rare Diseases
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