28 February 2011 print
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France celebrates International Rare Disease Day with the release of its second national plan for rare diseases
Today is our day and all around the world campaigns and conferences, petitions and press conferences, galas and games, marches and meetings are unfolding in a bid to raise awareness for rare diseases and this year’s special focus – Health Inequalities. In France, stakeholders have every reason to rejoice. The long-awaited second National Plan for Rare Diseases officially launches today after a series of delays and detours that lasted almost a year. France’s first national plan for rare diseases, which ran from 2005-2008, was the first initiative of its kind in the world and quickly became a model for other countries in Europe and beyond. Thus, the release of the second French National Plan for Rare Diseases today benefits rare disease patients and professionals both in France and in other countries trying to delineate a strategy for their rare disease patients. The next issue of OrphaNews Europe will provide details of both the new French plan and all the exciting activities held around the world this rare disease day.

Happy Fourth International Rare Disease Day from the staff of OrphaNews Europe!


EUCERD update
Rare diseases and Inequality…
A perspective from the European Union Committee of Experts on Rare Diseases


That’s not fair!” seems to be the universal battle cry of childhood. Where does it come from, the innate desire for justice and fairness that children possess? At what point do we relinquish our ideals and accept that, life, indeed, is not very fair? How many of us have been guilty of informing a child, “That’s too bad. Life isn’t fair!”?

The theme of this year’s International Rare Disease Day, initiated by Eurordis in 2008, asks that we reach inside ourselves and retrieve that lost idealism of childhood – with its imperative that life be fair, that equality should prevail, and we should all be awarded equal – if not identical – portions of life’s pie. Specifically, today, 28 February, stakeholders are asked to contemplate, and if possible to take some small measure toward correcting, the gaps in healthcare that exist - not only between countries but between illnesses.

Let it begin with us…
The various inequalities that exist between the world’s countries are so devastatingly enormous that it is easy to give up before we’ve even contemplated doing something about it. But a house is built slowly - brick by brick – and, likewise, change toward equality occurs action by action. The priorities of the European Union Committee of Experts on Rare Diseases (EUCERD) directly revolve around reducing inequalities for rare disease stakeholders – not only the patients and their families – but also for the health professionals, researchers, and policymakers who often find themselves with their hands tied, unable to provide help or resources. A sturdy foundation for change has already been laid with the adoption of a Council Recommendation on an Action in the Field of Rare Diseases, which calls on each European Union Member State to elaborate and adopt a rare disease strategy by the end of 2013.

Just what are we dealing with?
In order to alleviate inequalities in healthcare systems, it is first necessary to have solid data on existing rare disorders in the communities. A country cannot make rare diseases a priority if it has never been able to assess the number and nature of the conditions within its jurisdiction. The EUCERD is dedicated to the implementation of Community activities in the field of rare diseases, in cooperation and consultation with the specialised bodies in Member States, the relevant European authorities in the fields of research and public health action and other relevant stakeholders acting in the field. Current priorities are geared toward improving knowledge – what diseases are out there? What is the nature of these diseases? What resources already exist? These questions can be answered by improving the traceability of rare diseases via an updated International Classification of Diseases, for example, that assigns a code to each rare disease and can be cross-referenced with other classification systems. Other efforts include identifying existing documentable indicators for rare diseases and cataloguing the incentives and initiatives underway at the local or national level for rare disease patients. These actions contribute toward the reduction of inequality by capturing the existing state-of-play in the field and identifying gaps.

Inequalities in health
Having a rare disease should not automatically translate into a sentence for living a diminished life. This year’s International Rare Disease Day theme draws attention to the inequalities rare disease patients suffer due to the very nature of their illnesses. Rarity makes knowledge hard to obtain; rarity renders research fragmented or unpursued; rarity leaves treatments undeveloped. Perhaps worse, by driving prices impossibly high, rarity causes developed treatments to remain inaccessible to many. Yann Le Cam, leader of the patient-driven European Organisation for Rare Diseases qualifies the field of rare diseases as “…one of the most dramatic cases of health inequalities today both internationally and in particular in Europe”.

The EUCERD fully endorses the International Rare Disease Day campaign to raise awareness for the health inequities in the field – and particularly supports the promotion of rare diseases in the Third EU Public Health Programme (2014 to 2020) - and will continue working hard to level the playing field for all the rare disease stakeholders out there.


Spotlight on...
Spain’s McArdle disease database demonstrates that funding for registries is money well spent
Dr. Antoni L. Andreu, Head of the Neuromuscular and Mitochondrial Diseases Research Group, Vall d’Hebron Research Institute
McArdle disease is a myophosphorylase deficiency, also known as glycogen storage disease type 5. It is a severe glycogen storage disease characterised by exercise intolerance. Patients typically present with a syndrome of muscular exercise intolerance with myalgia, cramps, fatigue, and muscle weakness. Massive elevation of creatine-kinase and rhabdomyolysis with myoglobinuria (dark urine) after exercise is noted in around 50% of patients, potentially leading to acute kidney failure. Prevalence has not been determined. The condition is caused by mutations in the PYGM gene (11q13), leading to muscle phosphorylase deficiency. Treatment is based on controlled physical training in order to develop mitochondrial oxidation capacities in muscles, and programmed glucose intake according to exercising periods.

Dr. Antoni L. Andreu, a researcher with the department of neuromuscular and mitochondrial pathology at the Vall d’Hebron Research Institute in Barcelona and a member of the Spanish Centre for Biomedical Network Research on Rare Diseases (CIBERER) specialises in mitochondrial diseases and has been studying McArdle disease since the mid-1990s. Dr. Andreu kindly agreed to discuss the Spanish McArdle disease database.

OrphaNews Europe: When was the Spanish national database for McArdle disease created?

Dr. Antoni Andreu: All McArdle patients in Spain are referred for genetic diagnostic to three reference centres, located in Madrid, Barcelona and Vigo. Local databases have been operating for about ten years within these centres. In 2010, within the framework of the Centre for Biomedical Network Research on Rare Diseases (CIBERER), we decided to bring together the information contained in these three individual databases, creating a single national registry.

OrphaNews Europe: What information is contained in the McArdle disease database? How was it determined which information should be included?

Dr. Antoni Andreu: The database contains information on epidemiological, clinical, genetic, and follow-up information for all patients registered. The design was developed according to criteria established by clinicians, geneticists and key members of the laboratories involved in the genetic diagnosis of these patients. To date, there is no harmonised approach to designing registry databases. A skeleton model needs to be developed at the European level that would allow for the ready exchange of information between datasets. Particularly when data are geared toward treatment, a harmonised, structured approach would allow for the sharing and coordination of information. We should probably move from the term “registry “to “database” - which implies the mathematical exploitation of information to move forward research, diagnostics and treatment. “Registry” implies simply the collection of information but in fact, we want to do something much more interesting by analysing the data and exploiting the findings to best help the patients.

OrphaNews Europe: Could you discuss some of the findings the national McArdle disease database has revealed?

Dr. Antoni Andreu: McArdle disease provides a good example of the advantages of creating a collaborative database. Previously, all the knowledge for this disease was found scattered at the local level from small series of patients. A database created via collaborative effort affords a larger patient population. The picture changed significantly with this larger source of information. For McArdle disease, the larger database has given us a different perception of many things – including the natural history of the disease. McArdle disease has been considered an adult onset disorder, but through the larger set of data, we realised that symptoms present frequently in childhood. This gives us more information in terms of diagnostics – for example, McArdle disease should be proposed as a differential diagnosis for symptomatic patients. Knowledge such as this can impact many areas – such as treatment outcomes.

OrphaNews Europe: Could you comment on the funding of the database?

Dr. Antoni Andreu: The database has been locally funded by McArdle disease projects via the three local laboratories. A Mobility fellowship from the Instituto de Salud Carlos III, the Spanish Funding Agency for Biomedical Research of the Spanish Ministry of Science and Technology, allowed me to move to Madrid for a few months in 2010 to coordinate the process of developing the national database. This did not entail a lot of money – it was mostly management funding, but in the long run, it has allowed us to learn significantly more about the disease.

Countries with small research budgets can get a good return from putting money into disease databases. I would say that for the registries, one plus one yields three. The information the database gives us has changed the picture quantitatively, as well as qualitatively, for this disease. It can be hard to convince local authorities that money is needed to maintain databases, but it is money well spent.

OrphaNews Europe: How many patients are currently registered in the McArdle disease database? Who has access to the data?

Dr. Antoni Andreu: Currently there are 240 patients registered with a complete record of their clinical and genetic characteristics. We believe that this is highly relevant. The largest series of patients reported in the literature so far does not contain more than 40-50 patients. Due to the characteristics of the Spanish Health System, through which patients are referred to reference centres, we believe that the database faithfully captures the picture of McArdle disease in our country.

As to access, in compliance with the requirements of Spanish law on privacy issues, all personal information is encrypted and only those professionals who have the express consent of the patient have access to personal information. There is open access to global clinical and genetic data (with no patient identification) available to the database managers in the three laboratories that created the registry.

OrphaNews Europe: How are new patients added to the registry?

Dr. Antoni Andreu: When a new patient is referred for genetic diagnosis to a single laboratory, and once the genetic study is completed, the database manager activates a local protocol to include the information in the database.

OrphaNews Europe: In which language(s) is the database maintained? Do other countries have registries for this disease?

Dr. Antoni Andreu: The language of the database is English. The information of the local databases was in Spanish, but in creating the national database and thinking forward to possible exploitation of the data in the future, we decided to adopt English. To my knowledge, except for a small registry in England, there are no other registries for this disease.

OrphaNews Europe: What are the advantages of a disease-based database?

Dr. Antoni Andreu: There is no question concerning the putative advantages of a disease-based database: knowledge of the natural history, epidemiological profiles, and studies of genotype-phenotype. In general such a dataset provides a much better picture of the disease, its natural history and its epidemiology.

OrphaNews Europe: How can research actions that support networking – such as national or international registries - positively impact the field of rare diseases?

Dr. Antoni Andreu: The more we know about our patients the better we will be able to treat them. Databases are essential for rare diseases as they are the only opportunity to put together isolated cases to create large canvases of a particular disorder.
Contact Dr Antoni Andreu


EU Policy News

Resolution on pharmacy prepared medicinal products adopted by the Council of Europe
Resolution CM/ResAP(2011)1 on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients was adopted by the Committee of Ministers of the Council of Europe on 19 January. Special needs can arise from factors such as patient age, medical condition, individual disposition or environmental factors. The resolutions help to harmonise the preparation of medicinal products in community and hospital pharmacies throughout Europe and address the added value of pharmacy preparations; the responsibilities of health-care professionals; the preparation process; the product dossier; labelling; the reconstitution of medicinal products in health-care establishments; and authorisation for pharmacies or licences for companies making preparations for pharmacies. An article appearing in the 3 February 2010 issue of OrphaNews Europe specifically discusses the use of compounded products for rare diseases.
Consult Resolution CM/ResAP(2011)1

DG Research
New infrastructure brings EU research into the OpenAIRE
The Open Access Infrastructure for Research in Europe (OpenAIRE) launched in December 2010 at the University of Ghent in Belgium, providing a network of open repositories offering free electronic access to the scientific papers of Seventh Framework Programme (FP7) and European Research Council projects in diverse fields – including health. A European Commission press release describes the launch as “… an important step towards full and open access to scientific papers that could, for example, allow patients with rare illnesses to have access to the latest medical research results, or provide scientists with real-time updates about developments in their field”. The new structure is part of a larger bid to develop research infrastructures and e-infrastructures that can help boost Europe's competitiveness. According to the press release, only 15%-20% of some 2.5 million research articles published annually are available via open access journals or repositories. OpenAIRE originates from a European Commission pilot initiative that was launched in August 2008. FP7-funded projects “are requested to deposit peer-reviewed papers in online repositories and to provide open access within 6 or 12 months after publication depending on the thematic area”. Increasing access is particularly good news for the fields of rare disease and orphan drug research, which depend on networking and collaboration to identify and bring together scattered resources and avoid duplication. It is hoped that the OPENAire infrastructure will particularly help those countries lacking research resources for their rare disease patients. Visit the OpenAire website

EMA issues guidance for stem cell-based medicines
The European Medicines Agency (EMA) has issued a reflection paper on stem cell-based medicines that encompasses the different types of stem cells used in medicines, and addresses considerations for the development of stem cell-based medicines. In particular, the document “stresses the fact that companies developing medicines including stem cells need to pay close attention to the way the medicines are manufactured, to make sure that the final medicine is as consistent and reproducible as possible”. The reflection paper also offers consideration for pre-clinical and clinical testing. Adopted by the EMA’s Committee for Advanced Therapies in January, the reflection paper was open for public consultation last year and was discussed at a public workshop last May. Stem cell-based medicines could potentially be used in the treatment of many rare diseases. Consult the Reflection paper on stem cell-based medicinal products
Good manufacturing practice database expands access to all Member States
EudraGMP is the Community database on manufacturing and import authorisations and Good Manufacturing Practice (GMP) certificates launched by the European Medicines Agency in April 2007. In July 2009 GMP non-compliance of manufacturers was added. Now a new version of the database has been developed that offers public access to information on manufacturing inspection by regulatory authorities from all the European Economic Area countries, including all the EU Member States, Iceland, Liechtenstein and Norway. The move represents a global effort of the EMA to increase transparency. According to a press release, the wider access will, “…improve the sharing of information between regulators and industry; aid the coordination of activities related to manufacturing authorisations and GMP certificates between regulatory agencies in different European countries; eliminate the need for industry to submit applications in paper form; and facilitate the sharing of information on the outcome of inspections in the EU with regulatory authorities elsewhere in the world”. The increased access is particularly welcome to the fields of rare diseases and orphan drugs, which depend upon the coordination and sharing of information and activities.
Visit the EudraGMP website

EMA invites expressions of interest for a transatlantic workshop on drug-related progressive multifocal leukoencephalopathy
The European Medicines Agency would like to hear from international experts and stakeholders interested in attending a workshop on drug-related progressive multifocal leukoencephalopathy (PML) taking place in London on 25-26 July 2011. The workshop, hosted by the EMA and co-chaired with the US Food and Drug Administration, will aim to find a common understanding of the PML research priorities by mapping ongoing research and identifying gaps, fostering funding and partnerships to conduct research to fill knowledge and research gaps; and agreeing on a mechanism to ensure information-sharing and regular stocktaking of research results, knowledge and knowledge gaps. Experts and stakeholders should send an expression of interest via email by 30 April 2011. Attendance is limited. Learn more

National & International Policy Developments
New report seeks to leave no rare disease patient behind in England
The Specialised Healthcare Alliance (SHCA) is an English coalition of 61 patient-related organisations supported by nine corporate members which campaigns on behalf of people with rare and complex medical conditions. As was reported in the 17 November 2010 issue of OrphaNews Europe, the SHCA recently issued a report entitled, “The Challenge of Rarity – Putting the N in the NHS”, which critiques the country’s new arrangements for health service commissioning for small patient populations and offers recommendations to enhance the approach to cost assessment of treatments for these patients.

Now, the SHCA has published a new report. “Leaving No One Behind: Delivering High Quality, Efficient Care for People with Rare and Complex Conditions” takes stock of recent developments in specialised commissioning and “identifies a series of key drivers in delivering improved care and value for people with rare and complex conditions”. These include building on the Carter Review of Commissioning Arrangements for Specialised Services in 2005/06 (which “…marked a watershed in the development of associated policy and has yielded real benefits for patients in the years that followed); the impetus of the patient organisations as a vehicle to “drive up standards”; improved patient-physician collaborations; the contribution of NICE quality standards; the development of multidisciplinary networks; outcome measures that maximise effectiveness and efficiency; and the development of patient registries with sharply focused datasets.
Consult the new SHCA report

Ontario expands compassionate use drug policy
Ontario, Canada is expanding its compassionate review policy to allow more patients with “rare clinical circumstances” to benefit. As of 19 January, the Ontario Public Drug Programs “…will consider covering drugs that have been reviewed by the Committee to Evaluate Drugs (CED) and where Ontario is in funding negotiations with the manufacturer. Previously, applicants could not be approved for coverage in cases where the CED had made a recommendation, but the ministry was still in negotiations with the manufacturer”. According to a press release, some 250 applications are reviewed annually under the Compassionate Review Policy. The expanded policy covers “requests to cover drugs in cases where an individual has been urgently hospitalized due to an immediate life, limb or organ-threatening condition and the requested drug therapy is directly related to the condition that resulted in the hospitalization”. Canada’s health care system is organised by province. Learn more about the expanded Compassionate Use policy
China joins the Human Variome Project in a big way
China has committed a whopping USD $300 million (€221.8 million) to the Human Variome Project (HVP) - an international consortium committed to reducing the burden of genetic disease on the world’s population by collecting information on genetic variation and its affect on human health. China – with a fourth of the world population – offers rich genetic diversity that has not been properly studied or catalogued. A press release on the HVP website states that “The new institute, based in Beijing, will leverage that diversity to build new—and supplement existing—databases that catalogue genetic variation within genes implicated in hundreds of genetic diseases”. The investment of China is by far the single largest financial commitment in the project to date. All of the monogenic diseases are rare conditions.
Consult the HVP 2010-2012 Project Roadmap

Other International News
US research programme for rare undiagnosed diseases bears first fruit
As was reported in the 4 June 2008 issue of OrphaNews Europe, the National Institutes of Health (NIH) in the USA created the Undiagnosed Diseases Program as a clinical research undertaking specifically designed for rare medical cases that elude diagnosis. The programme investigates cases referred to the NIH Clinical Center (the largest hospital in the world totally dedicated to clinical research) by physicians across the country and is designed to capitalise on the expertise of different NIH agencies, including the National Human Genome Research Institute (NHGRI), the NIH Office of Rare Diseases (ORD) and the NIH Clinical Center. Underway since May 2008, the programme has now reported its first major breakthrough. A published article appearing in the New England Journal of Medicine, describes how researchers have identified the genetic cause for a rare arterial calcification disorder. Mutations in the NT5E gene have been identified as a cause for arterial calcification due to CD73 deficiency (consult the PubMed abstract ). Since the Undiagnosed Diseases Program launched, more than 200 medical cases have been enrolled from over 1,200 sets of patient records submitted. The study culminating in the identification of the NT5E gene also involved research from the US National Heart, Lung, and Blood Institute, as well as the St. John the Baptist Hospital, Turin, Italy; University of California, San Francisco; and Great Ormond Street Hospital-University College, London, England.
Learn more

New FDA website helps regulated industries save time and resources
The U.S. Food and Drug Administration (FDA) has introduced a new Web resource called FDA Basics for Industry. Designed “to help companies and others save time and resources in their interactions with the agency … the website includes basic information about the regulatory process, including information that is frequently requested by industry”. As with the European Medicines Agency, the FDA is keen on improving transparency and the new initiative is one of several actions itemised in a report titled “FDA Transparency Initiative: Improving Transparency to Regulated Industry” (learn more). Increased transparency is particularly welcome for rare disease medicinal products, which depend on collaboration and coordination to avoid duplication of effort and to ensure that products are brought to market as efficiently and safely as possible.
Visit the FDA Basics for Industry website

Trendy Apps target disabilities too
The field of application software (Apps) is booming. Indeed, the century-old American Dialect Society named “App” the “Word of the Year” for 2010. The ubiquitous Apps are multiplying daily and the world of rare diseases and disabilities is not being left out in the cold. Dozens of Apps have been developed that directly or indirectly aid patients with autism, cognitive deficit disorders, speech and/or hearing impediments, physical disabilities and other rare conditions. Some favourites include Proloquo2Go (for speech disorders), First Then Visual Schedule, TapToTalk, AutismXpress, iCommunicate, and Grace. There are also APPs specifically designed for parents of children with intellectual or behavioural disorders, including the Individualized Education Program Checklist and the Behavior Tracker Pro. A mother of an autistic child has created a spread sheet of Apps that can be helpful for children with autism and other disorders.

New Syndromes

A syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis caused by SMAD3 mutations
Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. The authors delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. Mutations were identified in the SMAD3 gene, encoding a member of the TGF-β pathway essential for TGF-β signal transmission. These findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.
Read the PubMed abstract

Nat Genet ; 121-126 ; February 2011
Immunodeficiency disorder characterised by a lack of TCRαβ+ T cells caused by a mutation in the TRAC gene
The authors describe two families with an autosomal recessive inherited immunodeficiency disorder characterised by increased susceptibility to infection and autoimmunity. A mutation in the TRAC gene was identified.
Read the PubMed abstract

J Clin Invest ; 695-702 ; February 2011
An autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability caused by an AP-4 deficiency
This report describes an autosomal recessive form of spastic tetraplegic cerebral palsy with profound intellectual disability, microcephaly, epilepsy and white matter loss in a consanguineous family resulting from a homozygous deletion involving AP4E1, one of the four subunits of the adaptor protein complex-4 (AP-4).
Read the PubMed abstract

J Med Genet ; 141-144 ; February 2011

New Genes

Fanconi anaemia: a new subtype caused by SLX4 mutations identified
Read the PubMed abstracts
To read more about "Fanconi anemia"

Nat Genet ; 138-141 ; February 2011
Nat Genet ; 142-146 ; February 2011
Nat Genet ; 147-152 ; February 2011

Spondyloenchondrodysplasia: genetic deficiency of tartrate-resistant acid phosphatase associated
Read the PubMed abstract
To read more about "Spondyloenchondrodysplasia"

Nat Genet ; 127-131 ; February 2011
Nat Genet ; 132-137 ; February 2011
Anaplastic large cell lymphomas: recurrent translocations disrupt the expression of DUSP22 and MIR29
Read the PubMed abstract
To read more about "Anaplastic large cell lymphoma"

Blood ; 915-919 ; 20 January 2011
Verma-Naumoff dysplasia: IFT80 mutation, already identified for Jeune dysplasia, at cause
Read the PubMed abstract
To read more about "Jeune syndrome"
To read more about "Short rib-polydactyly syndrome, Verma-Naumoff type"

J Med Genet ; 88-92 ; February 2011
Anomalies of human testicular development: loss-of-function mutation in GATA4 at cause
Read the PubMed abstract
To read more about "46,XY disorder of sex development"

PNAS ; 1597-1602 ; 25 January 2011

Research in Action

Gene Therapy
Spinal muscular atrophy: intravenous scAAV9 delivery of a codon-optimised SMN1 sequence rescues mice models
Read the PubMed abstract
To read more about "Proximal spinal muscular atrophy"

Hum Mol Genet ; 681-693 ; 15 February 2011
Beta-thalassaemia: gene therapy by allele selection shows potential
Read the PubMed abstract
To read more about "Beta-thalassemia"

J Clin Invest ; Epub ahead of print ; 10 January 2011
Sanfilippo and hurler syndromes: safe, efficient, reproducible gene therapy of the brain in dog models
Read the PubMed abstract
To read more about "Mucopolysaccharidosis type 3"
To read more about "Hurler syndrome"

Mol Ther ; 251-259 ; February 2011
Therapeutic Approaches
Krabbe disease: mesenchymal lineage stem cells have pronounced anti-inflammatory effects in the twitcher mouse model
Read the PubMed abstract
To read more about "Krabbe disease"

Stem Cells ; 67-77 ; January 2011
Immune thrombocytopenia: amelioration by CD44 antibodies in a mouse model
Read the PubMed abstract
To read more about "Immune thrombocytopenic purpura"

Blood ; 971-974 ; February 2011
Pulmonary arterial hypertension: mesenchymal stromal cells expressing heme oxygenase-1 reverse the disease in mice
Read the PubMed abstract
To read more about "Pulmonary arterial hypertension"

Stem Cells ; 99-107 ; January 2011
Maple syrup urine disease: phenylbutyrate therapy shows promise in late-onset cases
Read the PubMed abstract
To read more about "Maple syrup urine disease"

Hum Mol Genet ; 631-640 ; 15 February 2011
Diagnostic Approaches

Cohen syndrome: extending the phenotypic and mutational spectrum of recessive disorders via whole genome arrays
Read the PubMed abstract
To read more about "Cohen syndrome"

J Med Genet ; 136-140 ; February 2011
Charcot-marie-tooth disease: subtypes and genetic testing strategies
Read the PubMed abstract
To read more about "Charcot-Marie-Tooth disease"

Ann Neurol ; 22-33 ; January 2011

Patient Management and Therapy

Chronic immune thrombocytopenia: a six month phase three study finds eltrombopag effective
This phase 3, double-blind, placebo-controlled study involving 197 adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30,000 per μL found that eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment.
Read the PubMed abstract

To read more about "Immune thrombocytopenic purpura"

Lancet ; 393-402 ; 29 January 2011
Hereditary haemorrhagic telangiectasia: international guidelines for the diagnosis and management
Hereditary haemorrhagic telangiectasia (HHT) also known as Rendu-Osler-Weber disease, is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. The goal of the international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. The overall guidelines process was developed using the AGREE framework, with a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts from eleven countries, including guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.
Read the PubMed abstract

To read more about "Rendu-Osler-Weber disease"

J Med Genet ; 73-87 ; February 2011
Fragile X syndrome: differential response to the mGluR5 antagonist AFQ056 via epigenetic modification of the FMR1 gene
Fragile X syndrome (FXS) is an X-linked condition associated with intellectual disability and behavioural problems. It is caused by expansion of a CGG repeat in the 5' untranslated region of the FMR1 gene. This mutation is associated with hypermethylation at the FMR1 promoter and resultant transcriptional silencing. FMR1 silencing has many consequences, including up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. mGluR5 receptor antagonists have shown promise in preclinical FXS models and in one small open-label study of FXS. The authors examined whether a receptor subtype-selective inhibitor of mGluR5, AFQ056, improves the behavioural symptoms of FXS in a randomized, double-blind, two-treatment, two-period, crossover study of 30 male FXS patients aged 18 to 35 years. No significant effects of treatment on the primary outcome measure, the Aberrant Behavior Checklist-Community Edition score were detected at day 19 or 20 of treatment. In an exploratory analysis, however, seven patients with full FMR1 promoter methylation and no detectable FMR1 messenger RNA improved, as measured with the ABC-C, significantly more after AFQ056 treatment than with placebo. The authors detected no response in 18 patients with partial promoter methylation. Twenty-four patients experienced an adverse event, which was mostly mild to moderately severe fatigue or headache.
Read the PubMed abstract

To read more about "Fragile X syndrome"

Sci Transl Med ; 64ra1 ; 5 January 2011

Orphan Drugs

A study of orphan drug failures uncovers the keys to success
An article published in the journal Drug Discovery Today analyses the designated orphan drug products that fail to make it all the way down the pipeline to obtain marketing approval. The study, Characteristics of Orphan Drug Applications That Fail to Achieve Marketing Approval in the USA, identified trial design, sponsor experience and interaction with the regulatory agency as factors associated with non-approval. Conversely, the authors distinguished two characteristics essential to the successful authorisation of orphan drugs. The first involves the choice of primary endpoint and target population. The authors assert that the “…selection of these trial variables must be made carefully” for orphan drug clinical trials. Secondly, the authors found that “…inexperienced companies (and companies developing innovative orphan drugs based on NMEs) might face extra challenges when designing and conducting these clinical trials, and these companies might benefit from active participation in dialogue with the regulatory authorities and utilizing the special incentives for regulatory assistance and advice that are offered by the FDA”. It should be noted that the European Medicines Agency similarly offers regulatory assistance and advice for orphan drug development.
Consult the PubMed abstract

Thirteen positive opinions for orphan designation at the February COMP meeting
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 13 positive opinions issued at the February 2011 COMP meeting for the treatment of:

- chondrosarcoma
- moderate and severe traumatic brain injury
- post-exposure prophylaxis of inhalation anthrax disease
- pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
- pre-eclampsia
- Leber congenital amaurosis
- retinitis pigmentosa
- mucopolysaccharidosis type VI
- Leber hereditary optic neuropathy
- acute myeloid leukaemia (two products)
- diffuse large B-cell lymphoma
- haemophilia B

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


Courses & Educational Initiatives

Rare Solid Cancers: An Introduction
Organised by the European School of Oncology in collaboration with the Rare Care project. This course, being held in Stresa, Italy from 31 March – 1 April 2011, will focus on all the main rare solid cancers of the adult. Rare cancers present particular challenges, such as organisation of care and methodology of clinical studies. Oncologists, epidemiologists and health administrators will particularly find this course useful.
For further details

European Advanced Postgraduate Course in Classical and Molecular Cytogenetics
This ten-day course held in February/March each year 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. The students will be trained to identify genetic abnormalities for diagnosis and prognosis, and for fundamental and applied research using both classical and molecular cytogenetic techniques. The course is co-organised by the European Cytogeneticists Association and two French Universities, either as a stand-alone course with only the theoretical part or as a University Diploma including both theoretical and practical training. For further details
ESH Enerca Training Course on Haemoglobin disorders: Laboratory diagnosis and Clinical Management
In association with the Thalassaemia International Federation, this course, being held from 1-2 April 2011 in Brussels, Belgium, will address: Thalassaemias - Clinical and Molecular Aspects; Laboratory Diagnosis in Thalassaemia Syndromes; Sickle Cell Disease: Clinical Aspects; Abnormal Haemoglobins; Epidemiology of Haemoglobin Disorders; and more.
For further details

Update in Neuromuscular Disorders
Being held from 13-16 June 2011, at the Clinical Neuroscience Lecture Theatre, National Hospital for Neurology and Neurosurgery, in London, this established paediatric and adult course is now in its fourth year. Topics to include: What’s new in Duchenne muscular dystrophy?; Cognitive and behavioural profile of Duchenne MD; Psychological effects of participation in clinical trials; Cardiac involvement in neuromuscular disease; Congenital muscular dystrophies; Mitochondrial disorders – classification and genetic basis; and much more.
For further details

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.
For further details

Orphan Academy 2011 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.
For further details

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?

Genetic Diseases of Children…Advancing Research & Care
Date: 7-9 March 2011
Venue: NY, USA

The conference will bring together over 1000 researchers, clinicians, affected families, government and industry leaders for the purpose of advancing research to improve health outcomes for children with genetic diseases.
For further details

Human Genome Meeting 2011: Genomics of Human Diversity and Heritable Disorders
Date: 14-17 March 2011
Venue: Dubai, United Arab Emirates

Including symposia on the Genetics of Heritable Disorders; Cancer Genomics; Inborn Errors of Metabolism and Therapy of Genetic Disorders; Computational Biology and Statistical Genetics for the Analysis of Human Disease; Genetics of Deafness & Neurologic Disorders; and Advances in Genetics of Heritable Disorders.
For further details

Optimal Role of Patient Organisations in Drug Development
Date: 24 March 2011
Venue: Amsterdam, Netherlands

A conference dedicated to how partnership with patient organisations can contribute to more efficient drug development. For industry, scientists, patient organisations, and policy makers.
For further details

3rd European Phenylketonuria Group Symposium - Advances and challenges in PKU
Date: 24-26 March 2011
Venue: Lisbon, Portugal

The aim of this meeting is to review the most important outcomes of research in the field and to provide a forum for participants to discuss solutions that can optimise patient management in clinical practice.
For further details

CliniGene Network of Excellence: Gene Transfer and Therapy: State of the Art and eCHiPS - European Conference on Human iPS
7-9 April 2011
Paris, France

In the first part of this event the latest clinical data will be presented and the CliniGene platform leaders will report on the outcome and integration of various technologies. The eCHiPS - European Conference on Human iPS, organised jointly with several EU-networks, aims to offer an open forum gathering specialists with expertise in various aspects, such as reprogramming techniques, iPS markers, quality controls, industrial production, GMP constraints, clinical perspectives, predictive toxicology and high throughput screening, standardisation and regulation among others. The goal of this pivotal meeting is to promote a broader European collective action on iPS cells.
For further details

World Orphan Drug Congress USA 2011
Date: 13-15 April 2011
Venue: Washington DC, USA

This commercial event will bring together industry leaders, government, and research organisations to address the opportunities and challenges for the commercialisation of drugs to treat rare diseases.
For further details

Awakening Australia to Rare Diseases: Global perspectives on establishing a coordinated approach to a national plan
Date: 18-20 April 2011
Venue: Freemantle, Western Australia

This symposium will bring international experts on rare diseases together with stakeholders nationally to work towards a rare disease strategy for Australia.
For further details

Second All-Russian Conference for Rare Diseases and Rarely Used Medical Technologies
Date: 21-22 April 2011
Venue: Saint Petersburg, Russia

The first conference was attended by over 450 people from 23 countries and 20 districts of the Russian Federation. Of interest to scientific experts in rare diseases, clinicians, social workers, representatives of non-profit and charitable organisations, and policy-makers, this year’s event includes plenary sessions on policy in the field of rare diseases; modern approaches to diagnostics and treatment; and much more. Deadline for abstract submission: 17 March 2011
For further details

Fourth International Congress of Myology
Date: 9-13 May 2011
Venue: Lille, France

Close to 1,000 participants coming from the five continents are expected to attend this conference to obtain an update on the scientific and medical advances made in muscle science and its related disorders. Two days will focus on fundamental science and two days on clinical research. The event will provide an opportunity to learn more about the numerous therapeutic avenues being explored and by the emerging clinical trials.
For further details

The Third Birt-Hogg-Dubé Symposium
Date: 11-12 May 2011
Venue: Maastricht, Netherlands

The aims of the Third Birt-Hogg-Dubé (BHD) Symposium are to communicate advances in the understanding, management and treatment of BHD syndrome and, for the first time, of hereditary leiomyomatosis and renal cell cancer (HLRCC), as well as to promote collaboration among researchers in these and related fields. Keynote talks, abstract presentations and a poster exhibition will cover basic and clinical research in BHD and HLRCC. Prizes for exceptional posters will be awarded. Additionally, there will be patient- and family-centred sessions. Deadline for abstract submissions: 15 March, 2011.
For further details

12th International Conference on Thalassaemia and the Haemoglobinopathies
Date: 11-14 May 2011
Venue: Antalya, Turkey

The main topics will include epidemiology and prevention; heart and vascular abnormalities; reproduction and pregnancy; quality care for quality of life; other haemoglobin disorders; haemopoietic stem cell transplantation; gene regulation and therapy; and much more.
For further details

Ninth European Paediatric Neurology Society Congress
Date: 11-14 May 2011
Venue: Cavtat (Dubrovnik), Croatia

The programme includes basic neuroscience and neurobiology, new treatment approaches in muscular disorders, neuro-othology and neuro-opthalmology, advanced critical care and ethics in paediatric neurology as well as practical clinical knowledge in the skills of electroencephalography and electromyography via comprehensive workshops.
For further details

First International Symposium on Childhood, Adolescent and Young Adult Hodgkin Lymphoma
Date: 12-14 May 2011
Venue: Arlington, Virginia USA

This event seeks to: provide a platform for global collaboration; establish networks of multidisciplinary caregivers; identify leaders for specific projects; promulgate tools for communication and collaboration; and develop standards of care for children with HL.
For further details

European Perspectives in Personalised Medicine
Date: 12-13 May 2011
Venue: Brussels, Belgium

This conference will bring together key stakeholders of the research community and the healthcare sector to identify the developments needed in order to contribute to the research for Personalised Medicine at European and national level, in the frame of the Innovation Union and beyond. Organised by the services of the European Commission (DG Research and Innovation) in consultation with major stakeholders, the objective of the conference is to contribute to the building of a vision for 2020 and to clarify the role of EU-funded research to support progress in the area of personalised medicine. Sessions include: the basics of personalised medicine; biomarkers, clinical trials, diagnostics and treatments; and uptake in healthcare.
For further details

Fifth Meeting on the Molecular Mechanisms of Neurodegeneration
Date: 13-15 May 2011
Venue: Milan, Italy

This International Congress is the Fifth Meeting of the series dedicated to the Molecular Mechanisms of Neurodegeneration in hereditary diseases. As in the previous edition, the Meeting is aimed at stimulating new and productive interactions among basic and clinical research groups involved in this exciting area of human genetics.
For further details

3rd Symposium on Disorders of Sex Development
Date: 20-22 May 2011
Venue: Lubeck, Germany

Disorders of Sexual Development (DSD) constitute a group of rare, mostly heritable disorders affecting the genito-urinary tract and in most instances also the endocrine-reproductive system. This symposium “From Gene to Gender” looks at what has been learnt and what is still needed. Sessions will focus on genetics, hormones and actions, phenotype modulation, clinical aspects and more.
For further details

Ninth Hereditary Hemorrhagic Telangiectasia International Scientific Conference
20-24 May 2011
Antalya, Turkey

This biennial conference, held since 1996, is attended by a multi-disciplinary, international group of clinicians, researchers and patient association representatives with the goal of advancing research and discoveries through multi-disciplinary "cross-fertilization" and international collaboration. An attendance of approximately 300 is expected.
For further details

VII International Conference on Rare Diseases and Orphan Drugs (ICORD 2011)
Date: 21-23 May 2011
Venue: Tokyo, Japan

A global meeting on international cooperation and public health policies focusing on research, diagnosis, development of and access to treatment and care for rare diseases. The VII ICORD Conference will offer a platform for the exchange of perspectives for medical and healthcare professionals, patients and patients’ groups, basic and clinical researchers, policy-makers, government officers and pharmaceutical, biotechnology and medical device industries. Deadline for abstract submission: 31 March 2011 .
For further details

European Human Genetics Conference 2011
Date: 28-31 May 2011
Venue: Amsterdam, Netherlands

Featuring sessions on mitochondrial diseases and neonatal screening, iPS cells, ciliopathy and brain, neurodegenerative diseases, genetic therapy, prenatal diagnosis, dysmorphology workshop, educational sessions on Marfan, Noonan, and Ehlers-Danlos syndromes, amongst others, and much more.
For further details

The World Orphan Drug Summit
Date: 31 May – 1 June 2011
Venue: Frankfurt, Germany

The World Orphan Drug Summit will tackle challenges that are currently slowing the development, market authorisation and patient access to orphan drug treatments. The event will focus on delivering in-depth discussion and practical solutions to provide participants with the strategies to grow their orphan drug business.
For further details

Eighth European Cytogenetics Conference
Date: 2-5 July 2011
Venue: Porto, Portugal

This meeting will provide the participants with an opportunity for not only contributing their knowledge and experience, but also for interacting with each other.
For further details

VI Cornelia de Lange Syndrome World Conference
Date: 27-31 July 2011
Venue: Copenhagen, Denmark

Offering a professional symposium during which the latest developments in research, care and treatment will be discussed, as well as a family conference.
For further details

Society for the Study of Inborn Errors of Metabolism – Annual Symposium 2011
Date: 30 August – 02 September 2011
Venue: Geneva, Switzerland

The main scientific programme includes a joint session with the International Society for Newborn Screening (ISNS), a session on adult metabolic diseases, creatine metabolism and related disorders, gene therapy, plenary and free communications sessions, and much more.
For further details

European Conference on Post Polio Syndrome
Date: 31 August – 02 September 2011
Venue: Copenhagen, Denmark

This international conference is being held by the European Polio Union, and The Danish Society of Polio and Accident Victims.
For further details

3rd International Symposium on Pheochromocytoma and Paraganglioma
Date: 14-17 September 2011
Venue: Paris, France

An opportunity to learn the state-of-the-art in pheochromocytoma and paraganglioma, to meet the leading experts in the field (coming from Europe, United States of America, Asia and Australia), to exchange and discuss the most recent research data as well as to develop international collaborative studies between clinical and/or academic research teams. This symposium takes place during a unique moment when key pathophysiological mechanisms and new therapeutic targets have been discovered and translated from bench to bedside. Deadline for abstract submission: 28 May 2011
For further details

5th International Conference on Birth Defects and Disabilities in the Developing World
Date: 24-27 September 2011
Venue: Lodz, Poland

The primary theme of the conference will be economics of healthcare and methods for establishing sustainable financial resources to implement programs of value to health and assure access to care. Other topics include integration of services into national primary health programs for care of neonates and children with birth defects and disabilities; monitoring risk factors for major defects globally; preconception care; and development of networks and partnerships for most efficient utilization of the limited resources.
For further details

Treat-NMD Global Conference
Date: 8-11 November 2011
Venue: Geneva, Switzerland

The conference will comprise a range of sessions addressing the challenges in the neuromuscular field, including: Delivery of future therapies; Biomarkers; Care considerations; Neuromuscular diseases and society; and Regulatory issues, orphan drugs and the rare disease field.
For further details

Second ASID Congress of the African Society for Immunodeficiencies
Date: 8-11 March 2012
Venue: Hammamet, Tunisia

This second congress – postponed from its original 2011 date - will be an excellent opportunity to strengthen the capacity of colleagues all over the continent to better diagnose and manage patients with PIDs. The commitment and contribution of international experts, societies and associations to this process is highly appreciated.
For further details


Press & Publications

Cognitive and Behavioral Abnormalities of Pediatric Diseases
This recently-published text provides a detailed account of intellectual, other neuropsychological and behavioural manifestations in paediatric diseases. Conditions discussed include the whole range of paediatric diseases - genetic syndromes, other congenital conditions, metabolic, endocrine, gastrointestinal, infectious, immunologic, toxic, trauma, and neoplastic, as well as sensory disabilities including deafness and blindness. Where possible, a "translational" approach is used, linking the behavioural and cognitive manifestations of these conditions, to the underlying structural, chemical or genetic abnormalities and their effect on the brain, and, in turn, on behaviour and cognition. At the same time, included are significant psychosocial factors. Together, those factors have a major effect on patients' performance, including school performance, and on their families. This book is unique in its extensive coverage of the major paediatric conditions and of the detailed neurological, neuropsychological and behavioural aspects of each condition.

Title: Cognitive and Behavioral Abnormalities of Pediatric Diseases
Authors: R. Nass, and F. Yitzchak Frank -Eds
Publisher: Oxford University Press, March 2010
ISBN 13: 9780195342680

New German-language article looks at rare disease health policy milestones
Milestones of Health Policy and Rare Diseases is an article published recently in the German-language journal Klinische Paediatrie.
Consult the PubMed abstract


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
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Raphaël Demonchy, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Paloma Tejada, Aurélie Vandeputte
National Contact Point: Till Voigtländer (Austria), Jean Jacques Cassiman (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), Andres Metspalu (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann (Germany), Michael Petersen (Greece), János Sándor (Hungary), Andrew Green (Ireland), Judith Melki (Israel), Bruno Dallapiccola and Domenica Taruscio (Italy), Andre Megarbane (Lebanon), Vaidutis Kucinskas (Lithuania), Alfred Cuschieri (Malta), Abdelaziz Sefiani (Morocco), Martina Cornel (Netherlands), Stein Are Aksnes (Norway), Jolanta Sykut-Cegielska (Poland), Jorge Sequeiros (Portugal), Dragica Radojkovic (Serbia), Ludovit Kadasi (Slovakia), Borut Peterlin (Slovenia), Miguel del Campo and Manuel Posada de la Paz (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Habiba Chaabouni-Bouhamed (Tunisia), Fatmahan Atalar and Ugur Ozbek (Turkey), Edmund Jessop and Idoia Gomez-Paramio (United Kingdom)
For more information on the European Union Committee of Experts on Rare Diseases
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