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Final Europlan conference takes stock of the progress of Member State national strategies for rare diseases

On 25 February in Rome, Italy, the final conference of the Europlan project was held. Europlan, a three-year DG Sanco-funded project coordinated by the Italian National Centre for Rare Diseases (Instituto Superiore di Sanita) launched in April 2008, as an instrument to help the European Union Member States (MS) define a strategic plan for rare diseases following the adoption of a Council Recommendation on an Action in the Field of Rare Diseases that calls on the MS to elaborate and adopt a rare disease plan or strategy by the end of 2013. Europlan is an inclusive project, with 57 associated and collaborating partners - including clinicians, scientists, health authorities, and patient groups from 34 countries. The Europlan project created a “toolbox” designed to aid countries determine their priority areas and actions to include in a national plan. Some 15 individual EU countries hosted national conferences via the project. These conferences, designed to move forward the process of developing a national strategy for rare diseases, followed a format based on Europlan guidance documents. The final reports of these national conferences are available on the Eurordis website (consult the national conference final reports).

The European dimension
At the final Europlan meeting, it was observed that one of the strongest elements of the Europlan project was its role in adding the European dimension to individual national strategies. This point is critical to the field of rare diseases, which relies on coordination and collaboration at the European and international levels. The recent Eurobarometer survey results demonstrate that there is support for European cooperation (learn more). Catherine Berens (DG Research) adduced the E-Rare project as an effective strategy for the funding of collaborative research.

A Round Table meeting reviewed some of the overall results of the Europlan project such as its role in harmonising concepts and terminology between the MS and in helping to raise awareness at the MS level for key EU documents in the field of rare diseases and orphan drugs. During this session, the need for integrating the elements of the national rare disease plans into the national health care systems was discussed. The importance of mapping existing resources - which Orphanet, the pan-European information portal for rare diseases and orphan drugs, is doing – was also evoked. Other elements identified include the need for inclusivity – ie, involving all the various stakeholders in the development of a national plan; the need for the national protocols for diagnostics and care of a disease to include the provisions for patient coverage for testing and care; and the healthcare pathways – the multidisciplinary algorithms of care structured to support the implementation of clinical guidelines and protocols.

At the national level…
Discussion of the status of particular countries was also raised. While Bulgaria has a concrete plan, accessing funding remains problematic, especially in the area of diagnostics. Croatia hopes to put forward a plan in 2012. Denmark is in a period of regression, illustrated by the country’s information centre exclusively for rare diseases that has been extended to encompass all diseases. Greece has a plan on paper, but it is not yet legally recognised and the country has no national committee to implement it. There are also significant problems with access to orphan drugs in Greece. Starting a process to develop a plan in a country with 21 autonomous regions is a priority Italy – but the country’s organisation presents a daunting challenge. Italy also reports a long time for orphan drug approvals to be processed. The Netherlands is a country with a solid general health plan, which could explain why the Minister of Health is not in favour of developing a plan specifically for rare diseases. Furthermore, the country’s Steering Committee for Orphan Drugs is to be shelved at the end of 2011. In Poland, the process of elaborating a plan has not yet began, but awareness is increasing. Poland needs to focus on all elements of rare disease strategising – not just the orphan drugs. Spain does have a plan, but it has neither a budget nor a time-table. The UK seems to be moving forward, thanks in large part to the steam of the Rare Disease UK and similar patient-driven efforts.

A challenging dynamic
With several plans existing only on paper, other countries such as Denmark and the Netherlands reporting a regression, and other MS lacking resources, the dream that each MS will have a specific strategy to care for its rare disease patients, and which includes cooperation between the EU countries to share resources, is a fragile one. This is a critical time for each stakeholder to continue acting as a catalyst to push change forward. The recent adoption of the Cross Border Health Care Directive increases the need for concerted effort, with each EU country identifying its pockets of expertise and making them known, within the context of acknowledging and respecting the individual dynamic of each country, particularly its size and resources. Analysis of the results of this first Europlan project can help refine the second leg of the plan, which is being funded via the upcoming DG Sanco three-year joint action, Support to the implementation of national plans/strategies on rare diseases and related measures to implement Council Recommendation and Commission Communication on rare diseases. The second Europlan will continue to offer support and guidance to countries that have delineated a strategy and will aid countries that have not developed a plan to move forward, taking into account the specifics of each country in terms of size, prioritisation of measures and health care systems. There will also be an emphasis on the exchange of expertise between countries, as well as identifying outcome indicators that can be monitored. Twenty national conferences are being planned for the second Europlan.

Spotlight on...
Enthusiasm for Rare Disease Day sweeps across the world
According to statistics gathered by Eurordis, the patient-driven umbrella organisation for rare diseases and the brains behind the brilliant idea to launch a special day for rare diseases, this year’s International Rare Disease Day included 55 countries - up from 46 in 2010, 30 in 2009 and 18 the first year. Newcomers this year include Armenia, Iran, Mexico, Morocco, Nepal, Panama, Peru, Thailand, the United Arab Emirates, and Uruguay. Eurordis has partnerships with 22 national alliances and added Cyprus and Switzerland as new alliances joining the celebrations this year.

The official Rare Disease Day (RDD) website, maintained by Eurordis, received almost 50,000 visits from some 150 countries between 1 January and 3 March this year. On 28 February (RDD is celebrated on the last day of February each year) the site logged some 10,000 visits. The number of RDD friends leapt to 292 from 187 last year, including patients, patient organisations, caregivers, healthcare professionals, researchers, members of the biopharmaceutical industry and public authorities. Scores of testimonials addressing the subject of this year’s theme “Rare but Equal” were posted on the RDD website (view the Stories of Inequality). RDD was also active on the major social networking sites with over 14,000 fans on Facebook, 1,446 followers on Twitter, 432 photos posted on Flickr, and a hundred videos on YouTube.

Moving forward plans & policies
One of the most significant benefits of the awareness-raising day is the momentum the event provides for advancing the national plans that countries are urged to create following the Council Recommendation on an Action in the Field of Rare Diseases. Indeed, France took the occasion of RDD to unveil its second plan (learn more), and frameworks for strategies were evoked in Croatia, Hungary, and Ireland. Belgium chose the occasion to hold a symposium for the drafting of a national plan, and in Switzerland, a member of the Health Commission proposed a vote for a strategy.

Across the Atlantic, meanwhile, the U.S. Senate unanimously adopted a resolution officially designating 28 February, 2011 as Rare Disease Day in all states. The icing on the cake of recognition came from the Vatican when Pope Benedict XVI included a personal message to rare disease patients and families including a wish that advances in research will help patients.

Significant publications released in honour of RDD included the release of the Eurobarometer survey European Awareness of Rare Diseases Report (learn more). At the national level, the Rare Disease UK group released a major report outlining recommendations for a strategy for rare diseases (learn more). Luxembourg released a study undertaken by the Rare Disease Working Group entitled Rare diseases: A National Survey on the Situation of Persons with Rare Diseases in Luxembourg.

This year’s RDD also caused a stir in the press – including a 20 page supplement in the UK newspaper The Independent (view the supplement). Other leading country dailies and press agencies lending awareness for the rare disease cause on RDD include Les Echos (France), El Pais (Spain), Romania Libera (Romania), the Emirates News Agency, and the Cyprus Mail, for example. There were also publications and websites launched presenting the patient experience and perspective in Canada, Denmark, Georgia, Panama, and Russia.

At the EU level
At the EU level, the European Symposium- Rare but Equal- Addressing Health Inequalities for Rare Disease Patients in Europe was organised by Eurordis with the support of DG SANCO. Amongst the 86 participants were four representatives from the European Commission along with Member of Parliament Antonyia Parvanova, shadow rapporteur on the recently adopted EU Directive on Cross-Border Healthcare and Patient Mobility (learn more). The symposium provided a venue for discussing the issue of health inequalities as well as strategies to remedy the inequalities rare disease patients endure. The Cross-Border Healthcare Directive was cited as a mechanism for levelling the field. The European Commission confirmed that diminishing rare disease health inequalities is a priority. Stefan Schreck, DG SANCO, Head of Unit for Health Information, evoked the EUCERD as an engine to facilitating better rare disease healthcare based upon the principles of equity and solidarity.

All this in just one day? What will next year’s Rare Disease Day bring!


EU Policy News
When the rare informs the common…
An article appearing in the European Journal of Human Genetics sets out recommendations developed via the Public and Professional Policy Committee of the European Society of Human Genetics (ESHG) in collaboration with EuroGentest and the Institute of Prospective Technological Studies, for genetic testing of common disorders. One key recommendation put forward in the article Genetic Testing and Common Disorders in a Public Health Framework is significant to the rare disease community:

Monogenic conditions can serve as examples for common complex diseases, both in strategies to identify etiological pathways and in strategies to develop health care in a responsible way.

Many common disorders have monogenic subsets, which by definition are rare (all monogenic diseases are rare). Of these, the authors note that… “By unravelling the contribution of monogenic subsets to the etiology of common disorders as well as the contributions of susceptibility genes to multifactorial etiology, including complex gene–gene and gene–environment interactions, this new research promises to give insights that might lead to refinement of diagnosis and more accurate prognosis, disease management and disease prevention in common complex disorders that are of major relevance for population health”.

Developing countries have a high prevalence of monogenic diseases, due in large part to elevated consanguinity. However, some developing countries are following the trend of western countries and prioritising the complex, often lifestyle-related disorders. The authors state that, “For developing countries, the first priority in genetics must be to offer diagnosis of, and care for children and adults with inherited disabilities associated with monogenic, high penetrant inheritance, followed by action for the prevention of related morbidity and mortality”.

In the Background Document to the ESHG Recommendations on Genetic Testing and Common Disorders, entitled Genetic Testing and Common Disorders in a Public Health Framework: How to Assess Relevance and Possibilities, the authors note that “Learning from health care for monogenic disorders and monogenic subtypes may help to decide on potential avenues of implementation or non-implementation in health care”.
Consult the abstract
Consult the abstract for the background document


National & International Policy Developments
Creating Hope: a new study depicts proposed legislation to incite drug development for rare paediatric conditions
The 15 September 2010 issue of OrphaNews Europe reported on new legislation proposed in the USA that would extend an existing incentive scheme for neglected tropical diseases to rare childhood disorders. S.3697, the Creating Hope Act of 2010 would build upon the 2007 FDA Amendments Act, which established a priority review voucher programme providing sponsors undertaking drug development for a neglected tropical disease with a “voucher” that allows them an expedited FDA review process for any other product in development – including blockbusters. Now, in an article appearing in the journal Science Translational Medicine, the authors discuss the details and ramifications of such legislation, which “…appears to represent an important addition to the armamentarium in pediatric drug development", along with other incentives for drug development for children.
Consult the PubMed abstract
Consult the bill proposal

Other European news
Hungary gets its own Treat-NMD website

Network of Excellence for neuromuscular diseases TREAT‐NMD has branched out to offer a Hungarian-language website. The new site features information, news and events on the neuromuscular diseases, a patient forum, and details for joining the Hungarian registries for Duchenne muscular dystrophy, Becker muscular dystrophy and proximal spinal muscular atrophy.
Visit the Hungarian Treat-NMD site

UK audit reveals genetic testing activity for 2009-2010
The Clinical Molecular Genetics Society (CMGS) seeks to advance the science of clinical molecular genetics, further public education and promote the quality of molecular genetic testing in the UK through training, education, research, data-collection and quality schemes. Similar to the French Biomedicine Agency report (see OrphaNews Europe 29 September 2010), the CMGS issues an annual audit of genetic testing activity. Such information is valuable to understanding the rare disease demand for testing and pre- and post-natal activity in this area.

The UK audit includes number of samples, number and type of disease, number and type of tests sent for analysis and staff/workload across laboratories. The 2009-2010 audit “...shows a continued growth in national activity for each of the postnatal, prenatal and predictive testing categories, an improvement in routine reporting times and encouraging data of the capturing and utility of activity…”.

Prenatal diagnosis reports were recorded for 120 different disorders, with 86% being for common aneuploidies. There were 12839 prenatal reports, of which 1744 were for disorders excluding aneuploidy. Non-invasive foetal sexing testing accounted for 19% of non-aneuploidy screening. Monogenic disorders include sickle cell anaemia (440), beta-thalassaemia (119), SMA type I (61), Duchenne muscular dystrophy (32), Huntington disease (25), craniosynostosis (9), and others.

For postnatal activity, there was a 31% increase in single gene disorders for 2009-2010. This jump reflects the inclusion of data from a new large volume provider. There was a mean number of 789 reports for fragile X testing across 18 providers. There was a mean number of 706 cystic fibrosis reports across 20 providers.
Consult the CMGS audit

Other International News
A new article exposes the Rare Disease Repurposing Database – designed to accelerate the development of rare disease products
An article appearing in the 14 July 2010 issue of OrphaNews Europe described the USA’s Rare Disease Repurposing Database (RDRD), created as a tool to encourage the development of treatments for rare conditions. A new article appearing in the review Briefings in Bioinformatics exposes the mechanics and rationale of this new resource and discusses the potential benefits of gathering diversely scattered information into one location in order to offer sponsors “… a new tool for finding special opportunities to develop niche therapies for rare disease patients”.
Consult the PubMed abstract


Ethical, Legal & Social Issues
Swedish study reports that children with chronic conditions have an elevated risk for physical abuse
Unsettling statistics have been reported in an article published in Acta Paediatrica. The authors found via a national cross-sectional study in Sweden that children with chronic health conditions are also at greater risk for physical abuse as well as for witnessing intimate-partner violence. The authors of the article Chronic Conditions in Children Increase the Risk for Physical Abuse – but Vary with Socio-economic Circumstances conclude that, “a wide range of chronic health conditions in children increased the risk for physical abuse. This indicates that certain factors unite this group of children, irrespective of the type of disability or degree of severity, but where a combination with socio-economic circumstances is of importance”. The study involving 2771 children in Sweden echoes earlier findings: the authors cite the results of three other studies, stating that the results are “…essentially unanimous – children with disabilities are at greater risk of experiencing all types of abuse than children without disabilities. Depending on study design and sample, the rate of neglect, physical abuse and sexual abuse has been estimated to be 1.7–7 times higher for children with disabilities compared to children without disabilities”. It has been previously reported that children with mental/intellectual disability are at the highest risk for abuse. The Swedish study, which did not particularly focus on rare chronic conditions, also found a positive correlation between income level and other socio-economic conditions.
Consult the PubMed abstract


Orphanet News
Orphanet–Italy celebrates its tenth birthday with a new directory of services

On the occasion of the tenth anniversary of Orphanet-Italy, an updated Italian Directory of Services, Annuario Orphanet delle Malattie Rare 2011, was presented at the Ministry of Health. In attendance was Italian Health Minister Ferruccio Fazio, as well as the Director of the Paediatric Hospital Bambino Gesù, which hosts the Italian Orphanet headquarters, Pr Giuseppe Profiti; Orphanet country coordinator and Scientific Director at Paediatric Hospital Bambino Gesù Pr Bruno Dallapiccola; President of Farmindustria (which financed this second book) Dr Sergio Dompé; and President of Uniamo FIMR – the Italian Federation for Rare Diseases, Dr Renza Barbon Galluppi. Pr Bruno Dallapiccola presented the Orphanet-Italy book as a volume addressed to a wide public: patients, researchers, industry, organisations, practitioners, students and the media. He also discussed the future development of Orphanet-Italy, including the new look of the Italian Orphanet national webpage, the beginning of a quality and certification path, and new perspectives offered by an ontological approach to the database. From 1 April the Orphanet project will be funded by a Joint Action between the UE and the Italian Ministry of Health. An interview with Pr Bruno Dallapiccola is available at the following link.


New Syndromes

A de novo 12q13.11 microdeletion with severe intellectual deficit, cleft palate, and high myopia
The authors report a de novo 12q13.11 deletion of 1.3 Mb in a 10-year-old dysmorphic girl with a multiple congenital anomalies/intellectual defi syndrome consisting mainly of severe intellectual deficit, cleft palate, and high myopia. The deleted region encompasses 16 RefSeq genes. Among these, it is hypothesised that haploinsufficiency of AMIGO2 is potentially responsible for the intellectual deficit of this patient, and of COL2A1 for the cleft palate and high myopia.
Read the PubMed abstract

Eur J Med Genet ; January-February 2011 ; 94-96
An 18q21.31 deletion with speech delay, intellectual deficit, sleeping problems, facial dysmorphism, and feet anomalies
The authors report a 797 kb de novo interstitial deletion of 18q21.31 in a 6-year-old boy with speech delay, intellectual deficit, sleeping problems, facial dysmorphism, and feet anomalies. Examination of the region showed two genes, TXNL1 and WDR7, to be involved in the deletion. Haploinsufficiency of these genes could potentially contribute to the phenotype. The patient has some clinical features that overlap with earlier described patients with a larger deletion of the distal part of chromosome 18q.
Read the PubMed abstract

Eur J Med Genet ; January-February 2011 ; 86-88
SC4MOL mutations, encoding a methyl sterol oxidase, cause psoriasiform dermatitis, microcephaly, and developmental delay
Defects in cholesterol synthesis result in a wide variety of symptoms, from neonatal lethality to the relatively mild dysmorphic features and developmental delay found in individuals with Smith-Lemli-Opitz syndrome. The authors report mutations in sterol-C4-methyl oxidase-like gene (SC4MOL) as the cause of an autosomal recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. This gene encodes a sterol-C4-methyl oxidase (SMO), which catalyzes demethylation of C4-methylsterols in the cholesterol synthesis pathway. C4-Methylsterols are meiosis-activating sterols (MASs). They exist at high concentrations in the testis and ovary and play roles in meiosis activation. An accumulation of MASs in this patient led to cell overproliferation in both skin and blood. SMO deficiency also substantially altered immunocyte phenotype and in vitro function. MASs serve as ligands for liver X receptors α and β, which are important in regulating not only lipid transport in the epidermis, but also innate and adaptive immunity. Deficiency of SMO represents a biochemical defect in the cholesterol synthesis pathway, the clinical spectrum of which remains to be defined.
Read the PubMed abstract

J Clin Invest ; Epub ahead of print ; 1 February 2011

New Genes

VACTERL association: de novo microduplication at 22q11.21 identified
Read the PubMed abstract
To read more about "VATER association"

Eur J Med Genet ; 9-13 ; January-February 2011
Leigh disease: NDUFA10 mutations cause complex I deficiency in a patient
Read the PubMed abstract
To read more about "Leigh syndrome"

Eur J Hum Genet ; 270-274 ; March 2011
Carnevale, Malpuech and Michels syndromes: mutations in lectin complement pathway genes COLEC11 and MASP1 at cause
Read the PubMed abstract
To read more about "Malpuech syndrome"
To read more about "Michels syndrome"
To read more about "Carnevale syndrome"

Nat Genet ; 197-203 ; March 2011
Nephronophthisis-associated ciliopathies: TTC21B contributes causal and modifying alleles across the ciliopathy spectrum
Read the PubMed abstract
To read more about "Jeune syndrome"
To read more about "Nephronophthisis-associated ciliopathy"

Nat Genet ; 189-196 ; March 2011

Research in Action

Fundamental Research
Neuroblastoma: RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target
Read the PubMed abstract
To read more about "Neuroblastoma"

PNAS ; 3336-3341 ; 22 February 2011
Clinical Research
Rett syndrome: two studies focus on skeletal features
Read the PubMed abstract
To read more about "Rett syndrome"

Ped Res ; 293-8 ; 359-64 ; April 2011
Acute lymphoblastic leukaemia: outcome features of CRLF2 deregulation
Read the PubMed abstract
To read more about "Acute lymphoblastic leukemia"

Blood ; 2129-2136 ; 17 February 2011
VACTERL association: long-term outcomes of adults
Read the PubMed abstract
To read more about "VATER association"

Eur J Med Genet ; 34-41 ; January-February 2011
Mucosulfatidosis: SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome
Read the PubMed abstract
To read more about "Mucosulfatidosis"

Eur J Hum Genet. ; 253-261 ; March 2011
Acquired haemophilia: proteolytic antibodies activate factor IX in patients
Read the PubMed abstract
To read more about "Acquired hemophilia"

Blood ; 2257-2264 ; 17 February 2011
Systemic sclerosis: lung tissues have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension
Read the PubMed abstract
To read more about "Systemic sclerosis"

Arthritis Rheum ; 783-794 ; March 2011
Congenital heart defects: prevalence and perinatal mortality in Europe between 2000 and 2005
Read the PubMed abstract
To read more about "Congenital heart malformation"

Circulation ; 841-849 ; 1 March 2011
Gene Therapy
Duchenne muscular dystrophy: one year treatment of morpholino antisense oligomer improves skeletal and cardiac muscle functions
Read the PubMed abstract
To read more about "Duchenne and Becker muscular dystrophy"

Mol Ther ; 576-583 ; March 2011
Mucopolysaccharidosis VI: long-term amelioration after AAV-mediated liver gene transfer in a cat model
Read the PubMed abstract
To read more about "Mucopolysaccharidosis type 6"

Mol Ther ; 461-469 ; March 2011
Mucopolysaccharidosis I: minicircle gene therapy with immune modulation permits long-term expression of α-L-iduronidase
Read the PubMed abstract
To read more about "Mucopolysaccharidosis type 1"

Mol Ther. ; 450-460 ; March 2011
Hemophilia A: efficacy and safety of long-term prophylaxis following liver gene therapy in severe dog models
Read the PubMed abstract
To read more about "Hemophilia A"

Mol Ther ; 442-449 ; March 2011
Therapeutic Approaches
Haemophilia A: effect of B-cell depletion on tolerance induction to factor VIII (FVIII) in a mouse model
Read the PubMed abstract
To read more about "Hemophilia A"

Blood ; 2223-2226 ; 17 February 2011

Patient Management and Therapy

Prader Willi syndrome: adult patients have adverse psychiatric effects with rimonobant
Prader Willi syndrome (PWS) without strict environmental modifications can lead to obesity associated with significant morbidity and mortality. In addition to increased appetite, these individuals have decreased energy expenditure with lower insulin like growth factor 1 (IGF1), which contributes to adiposity. Endocannabinoid receptor CB1 antagonist, rimonobant, has been effective for treatment of obesity in adult subjects. In this double blind placebo controlled study, 50% of subjects in the rimonabant group withdrew due to psychiatric adverse effects and the study was terminated early for safety concerns. There was a trend for weight loss, lower fat mass and higher IGF1 level at the end of study in this group. Future CB1 antagonists will need a better psychiatric profile before considered in the treatment of obesity in this genetic condition.
Read the PubMed abstract

To read more about "Prader-Willi syndrome"

Eur J Med Genet ; 14-18 ; January-February 2011
Limited cutaneous systemic sclerosis: modified-release sildenafil reduces Raynaud's phenomenon attack frequency
In this double-blind, placebo-controlled study, 57 patients with Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis (lcSSc) were randomised to receive modified-release sildenafil 100 mg once daily for 3 days followed by modified-release sildenafil 200 mg once daily for 25 days or placebo. The primary assessment was the percentage change in the number of RP attacks per week. The mean number of attacks per week improved from 25.0 at baseline to 19.3 after placebo treatment and from 30.5 to 18.7 after modified-release sildenafil treatment. These findings indicate that modified-release sildenafil reduced attack frequency in patients with RP secondary to lcSSc and was well tolerated.
Read the PubMed abstract

To read more about "Limited cutaneous systemic sclerosis"

Arthritis Rheum ; 775-782 ; March 2011
Muckle-Wells syndrome: efficacy and safety of anakinra therapy in paediatric and adult patients
Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease caused by mutations in the NLRP3 gene that result in excessive interleukin-1 (IL-1) release. A single-centre observational study was performed in which 12 patients with severe MWS (5 children and 7 adults) received anakinra for a median of 11 months. The median follow-up was 11 months. Anakinra was found to be a safe and effective treatment of severe MWS, leading to a significant improvement in disease activity at two weeks as well as long-term.
Read the PubMed abstract

To read more about "Muckle-Wells syndrome"

Arthritis Rheum ; 840-849 ; March 2011
Six new Clinical Utility Gene Cards available
EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases. The European Journal of Human Genetics has published six new Clinical Utility Gene Cards for:

Axenfeld–Rieger syndrome
Silver-Russel syndrome
Bardet–Biedl syndrome
Laing distal myopathy

Learn more about the CUGCS


Orphan Drugs

Belgian study calls for a balance between rapid access to orphan drugs and assurance of quality, efficacy and safety
A Belgian study published in the British Journal of Clinical Pharmacology compared the quality of data between orphan products and innovative medicines for severe common disorders by performing a quality analysis of the clinical evidence in the reimbursement files via the country’s National Health Insurance Agency administrative database. Comparing the outcome decisions between orphan drugs and other innovative products for common diseases with comparable severity, the authors report that 88% of the orphan drug submissions received reimbursement versus 63% of the non-orphan drugs. However, only 52% of the orphan drugs had a randomised control study, versus 84% of the innovative non-orphan submissions. The authors of the article entitled Access to Orphan Drugs Despite Poor Quality of Clinical Evidence, assert that “Lower quality of evidence of clinical efficacy and safety, more uncertainty on cost-effectiveness and higher product prices are accepted for orphan drugs”. Rare disease drug trials by their nature suffer from sparse, scattered patient populations. The authors acknowledge that, “Assessing the therapeutic value of orphan drugs is more difficult than of other innovative medicines because of the rarity of patients, the disease severity and the heterogeneity and the scarcity of clinical experts”. The study calls for “…collaboration between the European Commission, competent for market authorization, and the EU member states, competent for reimbursement, in assessing the therapeutic risks and benefits of orphan drugs, to reduce the evidence gap post marketing”.
Consult the PubMed abstract

Orphan drugs: the key to recovery and stability in a post-blockbuster world?
A free-access article published in the Journal of Pharmacy and Bioallied Sciences discusses Orphan Drug: Development Trends and Strategies, exploring the current economic climate for the biopharmaceutical industry as the niche-busting orphan drug market picks up momentum. The authors observe that the “Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market”. The article, written by industry stakeholders from India, pays particular attention to the Asian perspective – discussing briefly the status of rare diseases in India, Taiwan, Singapore, Hong Kong, and Korea.
Consult the free-access article

When size really does matter: empowering the small clinical study
A nifty article published in Pharmaceutical Statistics touches upon topics useful to small trial design and analysis, including type of study; mitigating bias; study design; ethical issues; and statistical analysis considerations. The authors concur with the recommendations put forward in the Institute of Medicine report, Small Clinical Trials: Issues and Challenges (2001), which describe approaches for the design and analysis of small sample studies that can yield reliable and valid results (learn more). Clinical studies for rare diseases frequently involve small numbers of patients.
Consult the PubMed abstract


Courses & Educational Initiatives

32nd Annual Course of Pediatric Dermatology
The Course of Pediatric Dermatology, founded 30 years ago, lasts four days, this year from 26-29 April 2011 and is being held in Arcachon, France. It is designed for dermatologists and paediatricians in training (internal and senior registrars) or as a continuing medical education instrument, for all who want access to advanced training in the specialty. The themes have a rotation which varies according to topicality and importance of the subject, but a 4-year cycle provides a fairly comprehensive overview of dermatology of the child. The course will offer two days of content in English language and two days in French. As every year, a number of rare genetic diseases of the skin will be covered.
For further details

Upcoming European School of Genetic Medicine courses
The European School of Genetic Medicine offers advanced training in the fields of genetics and genomics in medicine. Upcoming courses include the Course in Cognitive Disorders (11‐13 April 2011); the Course in Next Generation Sequencing for Rare and Common Genetic Disorders (14‐17 April 2011); and the 24th Course in Medical Genetics (18‐22 May 2011). The European Society of Human Genetics (ESHG) is offering a certain number of fellowships covering the registration fee for these courses.
For further details

The Science of Small Clinical Trials Course – online participation possible
Created jointly by the FDA's Office of Orphan Products Development and NIH's Office of Rare Diseases Research, the Science of Small Clinical Trials Course addresses issues arising in the design and analysis of clinical trials based on small study populations. While small clinical trials are a necessity in the context of rare diseases, being able to conduct small trials with scientific rigor is of increasing importance in other contexts, particularly as genomic science begins to provide opportunities for individualised pharmacology. Eight 90-minute lectures will be held between 19 April and 12 May 2011. On-site or on-line attendance is possible.
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?

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

II 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.
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.
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

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

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

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

International Conference on Inherited Disorders of Muco‐Ciliary Clearance (Focus on PCD)
Date: 20-22 May 2011
Venue: Muenster, Germany

Genetic disorders affecting muco‐ciliary clearance are rare but burdensome for affected patients. Very recently a magnitude of distinct Primary Ciliary Dyskinesia (PCD) variants and their genetic background have been identified. This disorder is also known as immotile cilia syndrome or Kartagener Syndrome. This conference will gather leading scientists and physicians involved in the diagnostics and treatment of patients with PCD, as well as affected persons.
For further details

Ninth Hereditary Hemorrhagic Telangiectasia International Scientific Conference
Date: 20-24 May 2011
Venue: 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

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

9th International Prenatal Screening Group Congress
Date: 19-21 June 2011
Venue: Barcelona, Spain

This congress brings together laboratory providers, researchers, maternal foetal medicine specialists, geneticists and others interested in the provision of prenatal screening. The meeting will expand on the past meetings of the International Down Syndrome Screening Group through the inclusion of screening for disorders with a Mendelian pattern of inheritance and other single gene disorders, identification through maternal serum biochemical markers, foetal nucleic acids in maternal circulation and ultrasound, early detection of pregnancy complications and other conditions.
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

Tuberous Sclerosis Complex Scientific Day
Date: 14 October 2011
Venue: Paris, France

This meeting will be an opportunity for doctors and researchers to meet, to advance common projects in order to improve care of TSC patients. Participants desiring to present their work will be offered an opportunity to do so during a specific session in the end of the day.
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

German language study compares authorisation and reimbursement of orphan drugs
A study published late last year in the German-language review Gesundheitswesen compares eight countries (Australia, Canada, Germany, Great Britain, France, Netherlands, Switzerland, and the USA) in terms of their orphan drug regulations for authorisation, health technology assessment, reimbursement, and off-label and compassionate use practice. The authors found that, “In addition to common reimbursement practices, special schemes or programmes for the reimbursement of high-priced orphan drugs exist in all countries that were analysed”. They evoke the “rule of rescue” and/or “no cure, no pay” strategies as possible solutions to the growing conflict between promoting orphan drug access and the high costs incurred.
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, Kate Bushby, Catherine Berens, Helena Kaariainen, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Christophe Roeland

EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Radka Tincheva (Bulgaria), Ivo Baric (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek Jr. (Czech Republic), Marianne Jespersen (Denmark), Inna Vabamae (Estonia), Helena Kaariainen (Finland), Alain Garcia (France), Birgit Schnieders (Germany), Christos Katamis (Greece), Janos Sandor (Hungary), Sveinn Magnusson (Iceland), John Devlin (Ireland), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Jonas Bartlingas (Lithuania), Yolande Wagener (Luxembourg), Maria-Louise Borg (Malta), Harry Seeverens (Netherlands), Stein Are Aksnes (Norway), Jakub Adamski (Poland), Luis Nunes (Portugal), Ana Maria Vladareanu (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Concepcion Colomer Revuelta (Spain), Michael Soop (Sweden), Sabina Gallati (Switzerland), Edmund Jessop (UK)
EUCERD ECDC Representative: Andrew Amato
EUCERD Patient Organisation Representatives: Dorica Dan, Torben Gronnebaek, Yann Le Cam, Christel Nourissier
EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolène Aymé, Jean Donadieu, Dian Donnai, Laura Fregonese, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Sophie Koutouzov, Gerard Wagemaker
EUCERD European Commission Participants: Catherine Berens, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Antoni Montserrat Moliner, Christophe Roeland, Stefan Schreck, Kerstin Westermark (EMA-COMP)
Orphanet Partner Country Representatives: Tamara F. Sarkisian (Armenia), Yvonne Zurynski (Australia), Till Voigtlander (Austria), Herwig Jansen (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann-Spangenberg (Germany), Michael Petersen (Greece), Sandor Janos (Hungary), Andrew Green (Ireland) Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbane (Lebanon), Viadutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequieros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Desirée 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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