19 March 2010 print
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Like another famous European creation, the new Committee of Experts on Rare Diseases will not be built in a day...

As was reported in the 9 December 2009 issue of OrphaNews Europe, the European Union Committee of Experts on Rare Diseases (EUCERD) was established following the publication of the European Commission decision of 30 November 2009 in the Official Journal of the European Union. A call for expressions of interest consequently was issued, with a closing date of 21 December 2009. The new Committee will consist of 51 members, including one representative coming from the ministries or government agencies responsible for rare diseases to be designated by the government of each Member State; four patient organisation representatives; four pharmaceutical industry representatives; nine representatives of ongoing and/or past Community projects in the field of rare diseases financed by the programmes of Community action in the field of health, including three members of the pilot European Reference Networks on rare diseases; six representatives of ongoing and/or past rare diseases projects financed by the Community Framework Programmes for Research and Technological Development; and one representative of the European Centre for Disease Prevention and Control. The Committee will elect a chairperson and three vice-chairpersons, with a one-year term of office, from different categories of members of the Committee.

Following this initial flurry of activity, events have since slowed to a halt. A bottleneck occurred around the establishment of the new European Commission - a process that was held up by various incidents, including a delay in the signing of the EU Lisbon reform treaty. Consequently, the EUCERD appointments have not yet been established and the first EUCERD meeting has now been postponed until May of this year. OrphaNews Europe is keeping its finger on the pulse and will inform readers of any stirring of activity around the new Committee. The European Union Committee of Experts on Rare Diseases replaces the European Commission’s Rare Diseases Task Force. Point 7 of the Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on Rare Diseases: Europe’s Challenges, recommends that the European Commission be assisted by a European Union Advisory Committee on Rare Diseases. Learn more about the new Committee of Experts on Rare Diseases

EU Policy News
Workshop brings rare disease stakeholders together to discuss the future rare disease research agenda in Europe

Amongst all the activities that took place in honour of the third international Rare Disease Day (see the 24 February 2010 issue of OrphaNews Europe), one event in particular served to move forward the agenda of research on the European front. A workshop co-organised by EURORDIS, and E-RARE, in partnership with the European Commission, Orphanet and the EuroPlan project examined the pertinent topic of Bridging Patients and Researchers to Build the Future Agenda for Rare Disease Research in Europe. Over 100 key stakeholders attended the workshop, which sought to identify the priorities and the means to developing a truly collaborative framework for forwarding research in the field of rare diseases and orphan drugs. After an opening address by Robert Madelin (DG Sanco) the first session addressed the expectations of rare disease research from the perspectives of both researchers and patients. In the afternoon, participants examined how to develop a strong policy in order to advance rare disease research. Contributing their expertise to these issues were Manuel Hallen (DG Research), Volker Straub (TREAT-NMD), Terkel Andersen and Yann Le Cam (EURORDIS), Ségolène Aymé (Orphanet), Manuel Posada (Instituto de Salud Carlos III), Kerstin Westermark (Chairperson of the Committee on Orphan Medicinal Products at the EMA), Sophie Koutouzov (E-Rare) and other many other rare disease heavyweights. With so much experience and dedication gathered in one room, participants were optimistic that research for rare diseases can successfully keep moving forward in Europe - with the involvement and input of all players.
View the speaker presentations

Reducing neural tube defects: European countries can do better

The International Federation for Spina Bifida and Hydrocephalus (IF) has issued a report examining the incidence of Neural Tube Defects (NTD) in certain European Union Member States (France, Germany, Italy, Poland, Spain, Sweden, and the UK) as well as the policies that govern their prevention and management. The report makes the point that “although the link between low levels of folic acid and Neural Tube Defects has been established for decades and the European Commission has recognised NTDs as one of the few rare diseases which is frequently preventable, European governments still refuse to introduce mandatory food fortification and fail to adequately inform women about the need to use supplements”. The report urges countries to take a more active role in assuring that women receive adequate levels of vitamin B9 (folic acid) prior to conception and in the first weeks of pregnancy: “Our report results suggest a consensus among EU member states on the need to reduce the NTD incidence and to end the reliance on abortions, and late termination of pregnancies, linked to this largely preventable birth defect. We applaud their efforts so far. However, we conclude that the right advice is NOT reaching the right women at the right time. We therefore call for a new focus on improving folate levels in all women of childbearing age. We believe that under the auspices of the Rare Diseases Recommendation and potentially through other policies, Europe could, and should, reinvigorate its efforts to eliminate preventable NTDs by giving the right advice, to the right women, at the right time”. The report was unveiled at an event hosted by MEPs Dr. Antoniya Parvanova, Ms. Edite Estrela and Ms. Ria Oomen-Ruijten and in the presence of relevant stakeholders from across Europe.
Consult the report


EMA hosts conference to commemorate ten active years of EU Orphan Drug Regulation
The European Medicines Agency will hold a conference to celebrate the tenth anniversary of the Orphan Drug Regulation implementation in Europe on 3-4 May 2010. The meeting will take place at the Agency’s offices in London. Ten years ago, Regulation (EC) No 141/2000 of the European Parliament and the Council on Orphan Medicinal Products came into effect. Since then, over 700 products have received orphan designation to treat a number of different rare disorders. This vital regulation, which came into effect in April 2000, established the criteria for orphan designation in the EU and delineated the incentives (including market exclusivity, protocol assistance, and access to the centralised procedure for marketing authorisation) that were developed in order to encourage the research, development and marketing of medicines to treat, diagnose or prevent rare diseases. The upcoming conference, entitled 10 Years of the Orphan Regulation in Europe, will feature plenary sessions, discussions and three parallel workshops: Development of products for rare diseases: incentives, reality and future direction; Research for rare diseases: translation into new drugs for rare diseases-the role of academic researchers; and Patients’ view on the Regulation’s implementation: what is still needed? The conference is one of a series of interesting events the EMA has put on its agenda. In late April, the agency will hold a workshop on Nanomedicines and then on 10 May, a workshop on Stem Cell-Based Therapies. To further commemorate the tenth anniversary of the Orphan Drug Regulation, members of the EMA’s Committee for Orphan Medicinal Products (COMP) have published an article in the journal Drug News & Perspectives that describes the pivotal role the EMA has played in supporting the mechanisms that foster orphan product development.
For details on the Orphan Regulation Conference and other EMA events
Consult the COMP article abstract

The EMA and FDA streamline annual report process for orphan designated products
The European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) moved their collaborative effort another step forward in late February with the introduction of an agreement that permits one single annual report to be submitted for orphan products designated in both the EU and the USA. Prior to this, sponsors with designations in both places were required to submit two separate reports detailing the progress of drug development, including “a review and status of ongoing clinical studies, a description of the investigation plan for the coming year, any anticipated or current problems in the process, difficulties in testing, and any potential changes that may impact the product’s designation as an orphan product.” In a press release, Professor Kerstin Westermark, the Chair of the EMA Committee for Orphan Medicinal Products observed that this new measure will provide each agency “with information in real time on any challenges arising during the development of products for rare diseases and will help identifying and acting on bottlenecks.” Each regulatory body will continue to conduct its own assessment of the reports filed in order to appraise whether information satisfies the legal and scientific requirements of each agency. The option of submitting a single annual report to both agencies benefits sponsors by reducing the duplication of efforts. The new measure, unveiled on the occasion of Rare Disease Day, is one of several streamlined initiatives the two agencies have undertaken in recent years as part of a transatlantic agreement designed to enhance cooperation between the two agencies.


National & International Policy Developments
German Genetic Diagnostics Act comes into effect
On 1 February of this year, a law passed by the German Bundestag regulating genetic testing in humans officially came into effect. The Genetic Diagnostics Act regulates the practice of testing on humans as well as the handling of samples and data but does not extend to testing and data/samples undertaken for research purposes. Notably, the legislation prohibits prenatal testing for diseases that typically have onset after the age of adulthood (age 18). All persons undergoing genetic testing for medical purposes must be offered counselling before and after testing. The scope of the regulation includes predictive, prenatal and postnatal genetic testing. The Act seeks to reduce discrimination and to enhance the quality of testing in Germany by stipulating that laboratories be accredited. An unofficial English-language translation of the Act is available on the website of European Network of Excellence EuroGentest .
New proposal offers ray of hope to an estimated 10 million rare disease patients in China
From its opening sentence, an article appearing in the 27 February issue of the Lancet offers hope that change is in the air for rare disease patients in China. The commentary article, entitled Rare Diseases and Legislation in China begins by noting that "Public awareness of rare diseases is increasing in China". The authors present a "conservative" figure of 10 million rare disease patients in the country of 1.3 billion. Despite this, the authors point out that "Very few agents used for rare diseases in developed countries have entered the Chinese formulary, and few such drugs are affordable without a supportive policy or health-care insurance". Change could now be on the wing, however, due in large part to the lobbying of rare disease organisations and the awareness-raising success of Rare Disease Day. A proposal under review by the National Peoples Congress of China "..describes the burden of rare diseases in China and the difficulties patients face, and suggests solutions. Proposals include: definition of Chinese rare diseases; establishment of reimbursement mechanisms and succour networks for screening, prevention, diagnosis, and treatment of rare diseases; importation of orphan drugs proactively by governmental agencies instead of passively waiting for drug applications from foreign companies; and support and encouragement of new drug research and development from the native pharmaceutical industry". Furthermore, China is currently reforming its health care system, including its insurance scheme, and rare diseases and orphan drugs may get improved visibility under the new plan. The authors, issuing from various medical, health and scientific organisations in China describe the eventual acceptance of the proposal as a "win-win" situation.
FDA creates a new position specifically for rare diseases within its Office of New Drugs

In the United States of America, the Food and Drug Administration has announced a new position within its Center for Drug Evaluation and Research’s Office of New Drugs: that of Associate Director for Rare Diseases. A press release explains that, “the Associate Director for Rare Diseases will serve as CDER’s focal point to the rare disease drug development community and assist stakeholders and developers of drug and biologic products in navigating the complex regulatory requirements for bringing safe and effective treatments to patients in need”. This new position complements the work undertaken by the FDA’s Office of Orphan Products Development. Learn more

Czech Republic expands its newborn screening to include 13 conditions
The Czech Republic has expanded its newborn screening programme to include 13 diseases, including congenital hypothyrosis; congenital adrenal hyperplasia; cystic fibrosis; phenylketonuria; hyperphenylalaninemia; maple syrup urine disease; glutaric aciduria type I; medium-chain acyl-CoA dehydrogenase deficiency; long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; carnitine palmitoyl transferase 1 deficiency; carnitine palmitoyl transferase 2 deficiency; and carnitine acylcarnitine translocase deficiency. There are follow-up clinical services available for all screened disorders.

Worldwide there is increasing variation between countries in their offer of newborn screening, and the topic is becoming increasingly fraught with debate as advances in technology outpace sound ethical, legal and social policies. Many experts fear that testing for conditions which may never manifest in patients and/or for which no treatment exists can do more harm than good. On the other hand, conditions that have a better outcome when treated promptly can lower a country’s overall health burden when diagnosed early. For more information (in Czech language)

Other European news
A new Europe-based registry for nephrotic syndrome is open for global participation

Last month, a new registry launched specifically for nephrotic syndrome, a rare condition characterised by marked proteinuria, reduced plasmatic levels of albumin, and potentially oedema. The Nephrotic Syndrome Registry will allow both paediatric nephrologists and parents to register data on nephrotic syndrome with steroid resistantance, nephrotic syndrome with steroid dependence, and/or nephrotic syndrome characterised by frequent relapses (this can include steroid sensitive nephrotic syndrome if accompanied by frequent relapse). Developed in collaboration with the European Society of Paediatric Nephrology, paediatric nephrologists from anywhere in the world are invited to register their patients. Data can include first manifestation, demographics, relapse, biopsy information, medical therapy, dialysis, transplantation, family history, genetic analysis and more. Use of the multi-purpose web-based registry is completely free, and can also be used by parents for managing hospital visits and registering data. For more information

A cry for help: study reveals need for restructuring genetic test services in Italy
Experts on behalf of the Italian Society of Human Genetics in Italy gathered data on cytogenetic and molecular genetic testing and counselling activity in the country and determined that “changes are needed to improve the organisation of genetic services”. The study revealed that of 278 centres surveyed only “twenty-eight percent of the total were certified according to quality standards”. Moreover, “the fetal karyotype was examined on either trophoblast or amniocytes in about one of every 4.4 pregnancies [and] only 11.5% of cytogenetic analyses and 13.5% of molecular tests were accompanied by genetic counselling”. The study gathered data from laboratories and services over a one-year period, including 217 molecular genetic and 171 cytogenetic laboratories, and 102 clinical genetic services. The authors of the study published in the review Genetic Testing and Molecular Biomarkers, recommend reorganising the structure for genetic testing in Italy, which they presently qualify as “oversized”, and improving quality management as well as access to pre- and post-test counselling. This study also makes a case for the necessity of transborder testing services, as a lack of availability to testing for rare genetic disorders in Italy was noted. Consult the abstract
Spain obtains its first orphan designation
The Spanish High Council for Scientific Research (CSIC) obtained an orphan designation from the European Medicines Agency for raloxifene hydrochloride for the treatment of hereditary haemorrhagic telangiectasia (HHT). It is the first time that a Spanish government agency has obtained an orphan drug designation. HHT, also known as Rendu-Osler-Weber syndrome, is an autosomal dominant disease characterised by anaemia, severe recurrent nosebleeds and gastrointestinal blood loss. Raloxifene hydrochloride activates the endothelial cells of two promoters genes directly involved in HHT. Besides CSIC, research participants include the Institute for Training and Research Marques de Valdecilla, the Biomedical Network Research Centre on Rare Diseases (CIBERER), the Spanish Ministry of Science and Innovation, the Ramón Areces Fundation and the support of the Spanish Association of Patients with HHT.
Other International News
USA workshop investigates a common structure for rare disease registries and biospecimen repositories

The workshop Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories and Clinical Data was sponsored by USA National Institutes of Health, Office of Rare Diseases Research, National Eye Institute, National Center for Research Resources, Patient advocacy groups and others in the private sector. The workshop was held in January and gathered international experts to examine the possibility of developing a web-based infrastructure that would incorporate the data from individual rare disease patient registries, biospecimen repositories, and clinical data into one platform. With harmonised common data elements, including standardised vocabulary and terminology, such a structure could serve as a powerful tool to further research collaboration. The event opened with plenary sessions devoted to a discussion of the common objectives of a collaborative, federated rare disease patient registry and a practical discussion of the nuts and bolts necessary to move such an initiative forward (standards, informatics, and information technology advances). Other notable sessions considered biospecimen repositories, the role of registries in clinical research, government regulatory issues, patient participation, and bioethical and legal issues. A summary of the meeting is in preparation and will be provided when available from the steering committee. Speaker presentations from the two-day event are available online .

International Serious Adverse Event Consortium releases third set of data on genetic basis of rare drug reactions
In mid-February, the U.S. Food and Drug Administration and the International Serious Adverse Event Consortium released a third set of data concerning the genetic basis of rare conditions developed in reaction to certain medicinal products. In particular, the data concern toxic epidermal necrolysis - a group of rare skin conditions that include Stevens-Johnson syndrome and Lyell syndrome. The genetic data may help to predict the risk of an individual in developing these complications. This new release of data complements information made available in December 2008 and May 2009. For further information

Ethical, Legal & Social Issues

Brazilian study asserts moral imperative for funding rare disease treatments
A report appearing in Portuguese-language review Cadernos de Saúde Pública investigates the “morality of public funding for highly expensive orphan drugs for treatment of rare genetic diseases” in Brazil. Applying principles of bioethics and taking stock of the country’s Unified National Health System, the authors set out to demonstrate the “moral obligation to provide public policies to ensure care for individuals with genetic diseases…”. The article goes on to recommend ways in which to implement and sustain policies “with an emphasis on resource allocation, targeting, and equity”.
Read the PubMed abstract

South Korean study demonstrates the universality of patient concerns
Genetic counselling is developing in many countries in response to the growing offer of genetic testing. An article appearing in the Journal of Genetic Counseling synthesises the experience of South Koreans undergoing genetic testing in order to better inform genetic counsellors of the issues of highest concern for patients and/or parents or other family members of patients. South Korea’s health system presents a Catch-22 for some rare disease patients: national health insurance does not extend to all rare conditions and while private health insurance is expanding to fill the void, certain conditions are not covered privately either. Furthermore, some patients lose their private insurance upon diagnosis. This is one amongst many concerns revealed by the authors, who analysed the contents of over 700 messages posted on 18 rare disease patient website message boards – including boards for Angelman, Turner, Rett, Ehlers-Danlos, velocardiofacial syndromes, retinitis pigmentosa, the Korean Alliance for Rare Diseases, and others. In general, three broad areas of concern emerged from the analysis - medical information (most prevalent), psychosocial support and social acceptance, and disease management information. The authors concluded that “While cultural, geographic, and political nuances exist and play an important role in the delivery of genetic services, South Korean families have medical, informational, and support concerns following a known or suspected genetic diagnosis that resemble those of patients in other countries”.
Read the PubMed abstract


EU Project Follow-up
EUROCAT revamps its website

EUROCAT, the European network of population-based registries for the epidemiologic surveillance of congenital anomalies funded under the European Commission DG Health Public Health Programme since March 2004, has reorganised its website. The revised site is organised around three principal themes: prevalence, prevention, and prenatal screening. There is also a section of information on clusters and themes. Visit the new EUROCAT website

EU project seeks to involve patient groups in clinical research
PatientPartner, a three-year project funded under the European Commission’s 7th Framework programme, is examining the participation of patient organisations in clinical trials, with a focus on paediatric clinical studies, the use of biobanks and ethical issues. Established by the Dutch Genetic Alliance, the European Forum for Good Clinical Practice, the European Genetic Alliances’ Network and the British Genetic Interest Group, PatientPartner believes that “involving patient organisations as equal partners at all stages of clinical trials contributes to research that is better adjusted to the real needs of patients”. Patient groups play an especially critical role in rare disease research. Following an on-line survey and a central workshop, the project has launched regional workshops on Defining the needs and means for more partnership between Patients, Patient Organisations and Other Stakeholders in Clinical Trials. The next workshop is being held in Athens, Greece and is open to representatives from Cyprus, France, Greece, Italy, Malta, Portugal, Spain and Andorra, Gibraltar, Monaco, San Marino, Turkey, Vatican. Learn more .

Orphanet News
Orphanet takes advantage of Google translation technology

A new option now available on the Orphanet website allows users to translate information pages into any of the 50+ languages offered by Google Translate (TM). Although automatic translators do not yet offer perfect word-for-word renditions, this new service allows users to benefit from the information Orphanet offers in their own language.


New Syndromes
Early onset obesity linked to a rare chromosome deletion
Two articles appearing in Nature report the discovery of a new chromosomal anomaly with severe early-onset obesity and insulin resistance. A deletion in the 16p11.2 region has been identified.
Read the first PubMed abstract
Read the second PubMed abstract

To read more about "Obesity syndrome due to chromosomal rearrangement"

Nature ; 666-670 ; 4 February 2010
Nature ; 671-675 ; 4 February 2010


New Genes

Osteochondritis dissecans: a missense mutation in the aggrecan C-type lectin domain causes dominant familial form
Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. The authors identified a missense mutation in the gene ACAN and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.
Read the PubMed abstract

To read more about "Osteochondritis dissecans"

Am J Hum Genet ; 126-137 ; 12 February 2010
X-linked intellectual deficit associated with autism, epilepsy, and macrocephaly has mutations in the small GTPase gene RAB39B
Intellectual deficit (ID) is a common and highly heterogeneous paediatric disorder affecting around 3% of the general population; at least 215 X-linked ID conditions have been described, and mutations have been identified in 83 different genes. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in ID. The authors report here the identification of mutations in the small GTPase RAB39B gene in two male patients.
Read the PubMed abstract

Am J Hum Genet ; 185-195 ; 12 February 2010
Diamond-Blackfan anaemia: ribosomal protein genes RPS10 and RPS26 are commonly mutated
Diamond-Blackfan anaemia (DBA), an inherited bone marrow failure syndrome characterised by anaemia that usually presents before the first birthday or in early childhood, is associated with birth defects and an increased risk of cancer. Although anaemia is the most prominent feature of DBA, the disease is also characterised by growth retardation and congenital malformations, in particular craniofacial, upper limb, heart, and urinary system defects that are present in approximately 30%-50% of patients. DBA has been associated with mutations in seven ribosomal protein (RP) genes. Now the authors report three distinct mutations in the RPS10 gene in five probands and nine distinct mutations of RPS26 gene in 12 probands.
Read the PubMed abstract

To read more about "Blackfan-Diamond disease"

Am J Hum Genet ; 222-228 ; 12 February 2010
Frank-Ter Haar syndrome: Disruption of the podosome adaptor protein TKS4 causes skeletal, eye, and cardiac abnormalities
Frank-Ter Haar syndrome (FTHS), also known as Ter Haar syndrome, is an autosomal-recessive disorder characterised by skeletal, cardiovascular, and eye abnormalities, such as increased intraocular pressure, prominent eyes, and hypertelorism. The authors have identified the SH3PXD2B gene encoding the TKS4 protein in seven FTHS families. No SH3PXD2B mutations were detected in six other FTHS families, demonstrating the genetic heterogeneity of this condition. Interestingly however, dermal fibroblasts from one of the individuals without an SH3PXD2B mutation nevertheless expressed lower levels of the TKS4 protein, suggesting a common mechanism underlying disease causation.
Read the PubMed abstract

To read more about "Frank-Ter Haar syndrome"

Am J Hum Genet ; 254-261 ; 12 February 2010
Rhabdoid tumour predisposition syndrome: germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family
Rhabdoid tumours of early infancy are highly aggressive with consequent poor prognosis. Most cases show inactivation of the SMARCB1 tumour suppressor, a core member of the ATP-dependent SWI/SNF chromatin-remodelling complex. Familial cases, described as rhabdoid tumour predisposition syndrome (RTPS), have been linked to heterozygous SMARCB1 germline mutations. The authors have identified inactivation of another member of the SWI/SNF chromatin-remodeling complex, its ATPase subunit SMARCA4 (also known as BRG1), due to a SMARCA4/BRG1 germline mutation and loss of heterozygosity by uniparental disomy in the tumour cells of two sisters with rhabdoid tumours lacking SMARCB1 mutations.
Read the PubMed abstract

To read more about "Rhabdoid tumor"

Am J Hum Genet ; 279-284 ; 12 February 2010

Research in Action

Fundamental Research
Phytosterolemia: mouse mutation of thrombocytopenia and cardiomyopathy provides means to study disease
The spontaneous mouse mutation "thrombocytopenia and cardiomyopathy" (trac) causes macrothrombocytopenia, prolonged bleeding times, anaemia, leukopenia, infertility, cardiomyopathy, and shortened life span. Homozygotes show a 20-fold decrease in platelet numbers and a 3-fold increase in platelet size with structural alterations and functional impairments in activation and aggregation. Megakaryocytes in trac/trac mice are present in increased numbers, have poorly developed demarcation membrane systems, and have decreased polyploidy. The trac mutation provides a new clinically significant animal model for human phytosterolemia and provides a new means for studying the role of phytosterols in hematologic diseases and testing therapeutic interventions.
Read the PubMed abstract

To read more about "Phytosterolemia"

Blood ; 1267-1276 ; 11 February 2010
Clinical Research
Brugada syndrome: results from the FINGER Brugada Syndrome Registry
Brugada syndrome is characterised by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.
Read the PubMed abstract

To read more about "Brugada syndrome"

Circulation ; 635-643 ; 9 February 2010
Addison disease: development of a disease-specific quality of life questionnaire
The authors have developed an Addison disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects and could be useful in trials of hormone replacement and management of patients.
Read the PubMed abstract

To read more about "Addison disease"

J Clin Endocrinol Metab ; 545-551 ; February 2010
Kallmann syndrome: a phenotypic comparison of patients with mono- and bi-allelic mutations in the PROK2 and PROKR2 genes
Both biallelic and monoallelic mutations in PROK2 or PROKR2 have been found in Kallmann syndrome (KS). The objective of the study was to compare the phenotypes of KS patients harboring monoallelic and biallelic mutations in these genes. Male patients carrying biallelic mutations in PROK2 or PROKR2 have a less variable and on average a more severe reproductive phenotype than patients carrying monoallelic mutations in these genes. Nonreproductive, nonolfactory clinical anomalies associated with KS seem to be restricted to patients with monoallelic mutations.
Read the PubMed abstract

To read more about "Kallmann syndrome"

J Clin Endocrinol Metab ; 659-669 ; February 2010
Oculocutaneous albinism: a comprehensive analysis reveals mutational spectra and common alleles in Chinese patients
Oculocutaneous albinism (OCA) is a heterogeneous recessive disorder with hypopigmentation in the skin, hair, and eyes. At least 16 genes have been identified as causative genes for human OCA. The authors screened 127 unrelated and unselected Chinese OCA patients and found that the spectrum of mutational genes and alleles of OCA is population specific. These results provide useful information for the establishment of an optimized strategy of gene diagnosis and genetic counselling of Chinese OCA patients.
Read the PubMed abstract

To read more about "Oculocutaneous albinism"

J Invest Dermatol ; 716-724 ; March 2010
Gene Therapy
Limb-girdle muscular dystrophy and Miyoshi myopathy: recovery of dysferlin deficiency by dual adeno-associated vectors
Deficiency of the dysferlin protein presents as two major clinical phenotypes: limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin is known to participate in membrane repair, providing a potential hypothesis to the underlying pathophysiology of these diseases. The authors split the dysferlin cDNA at the exon 28/29 junction and cloned it into two independent AAV vectors carrying the appropriate splicing sequences. Intramuscular injection of the corresponding vectors into a dysferlin-deficient mouse model led to the expression of full-length dysferlin for at least 1 year. Importantly, systemic injection in the tail vein of the two vectors led to a widespread although weak expression of the full-length protein. Injections were associated with an improvement of the histological aspect of the muscle, a reduction in the number of necrotic fibers, restoration of membrane repair capacity and a global improvement in locomotor activity.
Read the PubMed abstract

To read more about "Autosomal recessive limb-girdle muscular dystrophy, type 2B"
To read more about "Miyoshi myopathy"

Hum Mol Genet ; Epub ahead of print ; 25 February 2010

Patient Management and Therapy

Myelofibrosis with myeloid metaplasia: phase 2 study of an orally available JAK2 inhibitor
Few treatment options exist for patients with myelofibrosis (MF), and their survival is significantly shortened. Activating mutation of the JAK2 tyrosine kinase is found in approximately 50% of MF patients. CEP-701 is a tyrosine kinase inhibitor that inhibits JAK2 in in vitro and in vivo experiments. In this phase 2 clinical study of CEP-701 in 22 JAK2(V617F)-positive MF patients (80 mg orally twice daily) CEP-701 resulted in modest efficacy and mild but frequent gastrointestinal toxicity in MF patients.
Read the PubMed abstract

To read more about "Myelofibrosis with myeloid metaplasia"

Blood ; 1131-1136 ; 11 February 2010
Pachyonychia congenita: mutation-targeted siRNA phase Ib trial results promising
The rare skin disorder pachyonychia congenita (PC) is an autosomal dominant syndrome that includes a disabling plantar keratoderma for which no satisfactory treatment is currently available. The authors completed a phase Ib clinical trial for treatment of PC utilising the first short-interfering RNA (siRNA)-based therapeutic for skin. This siRNA, called TD101, specifically and potently targets the keratin 6a (K6a) N171K mutant mRNA without affecting wild-type K6a mRNA. The safety and efficacy of TD101 was tested in a single-patient 17-week, prospective, double-blind, split-body, vehicle-controlled, dose-escalation trial. No adverse events occurred during the trial or in the 3-month washout period. The callus regression seen on the siRNA-treated foot appears sufficiently promising to warrant additional studies of siRNA in this and other dominant-negative skin diseases.
Read the PubMed abstract

To read more about "Pachyonychia congenita"

Mol Ther ; 442-446 ; February 2010

Orphan Drugs
Ten new orphan designations from the COMP in March

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) issued ten positive opinions at the March 2010 COMP meeting for the treatment of:

- multiple myeloma
- renal cell carcinoma
- tuberculosis
- retinitis pigmentosa in Usher syndrome 1B
- prevention of delayed graft function in renal transplantation
- acute lung injury
- Merkel cell carcinoma
- prevention of sepsis caused by gram positive pathogens in premature infants less than or equal to 34 weeks of gestational age
- Hutchinson-Gilford progeria
- Gaucher disease
Consult the European Register of Designated Orphan Medicinal Products
Consult the Orphanet list of orphan drugs authorised for marketing in Europe

Shire metachromatic leukodystrophy trial halted
Shire HGT has issued a press release concerning the suspension of a trial involving intravenous enzyme replacement therapy for the treatment of metachromatic leukodystrophy. Shire plans to explore direct central nervous system delivery as a treatment route for this product. Consult the press release
FDA approves products for Gaucher disease and chronic lymphocytic leukaemia
The U.S. Food and Drug Administration (FDA) has approved velaglucerase alfa for injection (VPRIV) to treat children and adults with Type 1 Gaucher disease. VPRIV, manufactured by Shire Human Genetic Therapies Inc, is an alternative to Cerezyme (imiglucerase), which is currently in short supply. The FDA also approved Rituxan (rituximab), an anti-cancer drug intended for patients with chronic lymphocytic leukaemia (CLL) who are beginning chemotherapy for the first time as well as for those who have not responded to other cancer drugs for CLL. Rituxan, manufactured by Genentech, is administered with two other chemotherapy drugs, fludarabine and cyclophosphamide.

Call for proposals for research into histiocystic disorders
The Histiocytosis Association of America is a non-profit organisation dedicated to raising awareness for histiocytic disorders, providing educational and emotional support, and funding research leading to better treatments and a cure. Proposals are now being accepted from international participants for research into the causes and mechanisms of these disorders and improved means of treatment. Deadline: 1 July 2010
For further details


News from the Patients' Associations
Switzerland forms a national alliance for rare diseases
Following the example of many of its European neighbours, Switzerland has formed a national umbrella organisation for rare diseases, gathering dozens of individual patient groups into one alliance. It is estimated that as many as 500,000 residents in Switzerland suffer from a rare condition. Paediatrician and geneticist Loredana D’Amato Sizonenko, who also coordinates Orphanet-Switzerland, played a pivotal role in founding ProRaris - the country’s new national alliance for rare diseases. In comparison to other countries, creating an umbrella organisation in Switzerland is complicated due to the country’s three official languages. In a news article, Dr. Sizonenko observed that “Even if the diseases are different, the difficulties are common.” This common ground makes collaboration imperative; left on their own, most individual patient groups have too few members to make a significant impact. ProRaris thus provides patients a structure from which to lobby for needed policy changes in Switzerland. ProRaris also plans to coordinate its activities with EURORDIS, the European-level alliance for rare diseases. For further details

Courses & Educational Initiatives
23rd Course in Medical Genetics
Date: 23-28 May, 2010
Venue: EuroMediterranean University Centre of Ronzano, Bologna, Italy

A week-long postgraduate level course addressed to both researchers and clinicians seeking an up-to-date overview of the field of medical genetics today, providing an overall view of the clinical developments taking place in the major application fields of modern genetics in different medical specialties. The topics covered in the present edition are: Introduction to Medical Genetics and Genome Analysis, Cytogenetics and Clinical Genetics, New Approaches in Medical Genetics, Complex Genetic Disorders and Neurogenetics, Therapy, Technology, Epigenetics and Ethical Issues.
For further details

Update in Neuromuscular Disorders
Date: 24–27 May 2010
Venue: Clinical Neuroscience Lecture Theatre, National Hospital for Neurology and Neurosurgery, London, UK

This course, now in its third year, is the result of the merging of two popular annual courses with an established international reputation. Amongst the many topics covered are diagnostic approaches in muscular dystrophy; distal myopathies; limb girdle muscular dystrophies; long-term ventilation in DMD; childhood CMT; Pompe disease; congenital myopathies; congenital myasthenia; pharmacological treatment of muscular dystrophies; genetic therapy in DMD; and much more.
For further details

TREAT-NMD Clinical Trials in Neuromuscular Disorders and Other Rare Diseases Workshop
Date: 24-26 June 2010
Venue: The Clinical Trials Coordination Centre, Freiburg, Germany

One of the most common reasons for failed trials is poor protocol design. As neuromuscular disorders are very rare, clinical trials have to be multi-centre or even multinational to include enough patients. As a result, the study design for these trials is usually complex. Also, academic trials have come to face a changed regulatory environment following the implementation of the EU Clinical Trials Directive 2001/20/EC. This TREAT-NMD workshop will explore these issues.
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

Institute of Myology Summer Programme
The Institute of Myology offers the possibility to train in myology via a condensed 10-day course organised in Paris, France. The course is open to foreign students with special attention given to those posted in the French Overseas Territories and those working in developing countries. Many aspects of myology are addressed during the course, from basic science to cutting-edge therapies, and clinical and genetic approaches to muscle diseases, taught via a series of lectures and interactive workshops in English. A certificate of attendance is issued upon completion of the Summer School.
For further details


What's on Where?

Health 2.0 Conference
Date: 6-7 April 2010
Venue: Paris, France

The Health 2.0 Conference is the leading showcase of online and mobile technologies in healthcare – including rare disease information and care.
For further details

Sickle Cell: The Next 100 Years
Date: 14-16 April 2010
Venue: Leicester, United Kingdom

Sickle Cell: The Next 100 Years will mark the 100th anniversary since Dr James Herrick published his first observations on ‘peculiar elongated cells’, what is now known as sickle cell disease. This three day conference will bring together a selection of papers offering delegates the chance to explore the social research currently being carried out around the world.
For further details

ESH-EHA Conference: Innovative Therapies for Red Cell and Iron Related Disorders
Date: 16-18 April 2010
Venue: Cascais, Portugal

Sessions include: Hematopoietic stem cell therapies; molecular switching in erythroid differentiation; gene therapy; iron regulatory pathway for therapies; innovative therapies for red cell disorders, and more.
For further details

18th International Workshop on Vascular Anomalies
Date: 21-24 April 2010
Venue: Brussels, Belgium

Topics will include clinical and basic research in the pathophysiology, diagnosis and management of vascular anomalies, as well as the psychosocial challenges faced by the patients.
For further details

Birt-Hogg-Dubé syndrome Symposium 2010
Date: 22 April 2010
Venue: Washington, DC USA

A symposium for reviewing the latest developments for Birt-Hogg-Dubé syndrome.
For further details

4th International Meeting on Congenital Disorders of Glycosylation and Related Disorders
Date: 22-23 April 2010
Venue: Leuven, Belgium

Organised by EUROGLYCANET, a European network for the advancement of research, diagnosis and treatment of a growing group of rare disorders, this meeting will cover all aspects of these disorders, including the discovery of novel types, the study of fundamental aspects of glycosylation, analytical procedures and diagnostic methods and the analysis of models for the disease.
For further details

XI International Child Neurology Conference
Date: 2-7 May 2010
Venue: Cairo, Egypt

Featuring a rich variety of topics including epilepsy, new anticonvulsants, neurogenetics, CNS infection, nutritional disorders of CNS, demyelinating diseases and leukodystrophies, cerebellar ataxia, advances in spinal muscular atrophy, myasthenia gravis and myasthenic syndromes, neurocutaneous disorders, and much more.
For further details

European Medicines Agency Conference: 10 years of the Orphan Regulation in Europe
Date: 3-4 May 2010
Venue: London, UK

The aim of this conference is to bring together patients, researchers, industry and regulators to discuss and share experiences concerning the development of orphan medicinal products. Plenary sessions, workshops, and discussions will take place.
For further details

European Medicines Agency Workshop on Stem Cell-Based Therapies
Date: 10 May 2010
Venue: London, England

Gathering regulatory, academic, and industry experts to share their experiences in the development of stem cell-based cell therapies, within the context of Advanced Therapy Medicinal Products (ATMPs), this workshop will focus on scientific requirements specific to stem cell-based ATMPs. By fostering global dialogue in this innovative field of cell therapy, the EMA intends to stimulate the discussion on the requirements and methods considered acceptable for stem cell-based therapies and to support their development.
For further details

3rd Human Variome Project Meeting: Implementation and Integration
Date: 10-14 May 2010
Venue: Paris, France

This third Human Variome Project Meeting will discuss "Implementation and Integration" with the aim of determining how the recommendations and actions from the first meetings can be best implemented in a global collaborative context to prepare the systems necessary to routinely and systematically gather the deluge of variations in genes causing disease. This meeting will bring together key individuals, including bio-informaticians, clinical geneticists, researchers, counsellors, database curators, diagnostic laboratory heads, common disease variation experts, genome sequencers, support groups, and will address and include topics impacting clinical data collection, genetic data collection, distributed databasing (country and gene specific), country specific collection, key pilot/current projects, central databasing, transfer to central databases, incentives for databasing, ethics of databasing and funding.
For further details

5th European Conference on Rare Diseases 2010
Date: 13-15 May 2010
Venue: Crakow, Poland

“From policy to effective services for patients”, this conference will look at national plans and strategies for rare diseases, European reference networks and centres of expertise, information and medical education, science from bench to bedside, rare diseases in central and Eastern Europe, and much more.
For further details

7th International Prader-Willi Syndrome Conference: East Meets West – A New World for Prader-Willi Syndrome
Date: 20-23 May 2010
Venue: Taipei, Taiwan

A scientific conference bringing together clinicians and researchers from around the world to present and discuss new research findings relevant to the understanding of PWS, new treatments and support strategies, and policy and practice development will be held alongside and combined with a parent and care-provider conference. There is also a young persons’ programme designed especially by the host country.
For further details

22nd Annual Meeting of the European Academy of Childhood Disability
Date: 27-29 May 2010
Venue: Brussels, Belgium
This year’s event - Measures of Progress – Evaluating management outcome in childhood disability - will update and clarify the multidimensional model of disablement specifically applied to management of children with neurodevelopmental disability. Emphasis is on the need for reliable measurement of management outcomes through new findings, from functional imaging to quality of life assessment.
For further details

First International Workshop on Oesophageal Atresia
Date: 27-28 May 2010
Venue: Lille, France

Amongst the topics covered will be: molecular embryology of the foregut; environmental factors in the etiology of esophageal atresia; genetic factors in isolated and syndromic esophageal atresia; ultrasound and MRI prenatal diagnosis of OA: impact on management; Outcomes of esophageal atresia beyond childhood; multidisciplinary clinics: how to improve the follow-up of the patients; and family support groups: an essential contribution to follow-up care.
For further details

Fourth Conference on Translational Research in Paediatric Rheumatology
Date: 27-30 May 2010
Venue: Genoa, Italy

“Biological Agents and Emerging Treatments in the Management of Rheumatic Diseases” will address the treatment of both adult and childhood rheumatic diseases with the purpose of reviewing and discussing the progress that has been achieved thus far, the unmet needs that are still faced, and the potential new treatments that the future holds in store. A final session will be devoted to strategies to improve methodologies of translational research on and clinical development in common, as well as rare, forms of rheumatic disorders.
For further details

18th Biennial Meeting of the International Society for Developmental Neuroscience
Date: 6-9 June 2010
Venue: Estoril, Portugal

Will feature the most recent advances in fundamental and disease-focused developmental neuroscience. Fragile X, Rett Syndrome, ciliopathy disorders, and Meckel-Gruber syndrome are amongst the rare conditions included in the programme.
For further details

European Human Genetics Conference 2010
Date: 12-15 June 2010
Venue: Gothenburg, Sweden

In conjunction with the European Meeting on Psychosocial Aspects of Genetics. With various satellite symposia available including the one-day event taking place on 11 June entitled "Changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe".
For further details

International Conference on Neuromuscular Diseases: Care and Clinical Trials
Date: 17–19 June 2010
Venue: Sao Paulo, Brazil

This exciting meeting is aimed at healthcare professionals with an interest in neuromuscular disorders (with a special focus on DMD and SMA) and patients and families. Two days of lectures from a strong panel of international and Brazilian speakers will be followed by a dedicated family day with research updates for patients and information on physiotherapy and care.
For further details

11th International Symposium on Mucopolysaccharide & Related Diseases
Date: 23-26 June 2010
Venue: Adelaide, South Australia

This year’s theme is "Translating Research into Clinical Reality" with a focus on the areas of newborn screening, prognostics, understanding pathology and therapeutic options.
For further details

6th Alstrom Syndrome Family Conference, Medical Research Clinic and Scientific Symposium
Date: 24-28 June 2010
Venue: Helen, Georgia, USA

Bringing together patients and professionals to further knowledge of Alstrom syndrome and its treatment.
For further details

International Congress for Tarlov Cysts and Adhesive Arachnoiditis
Date: 2-3 July 2010
Venue: Chambéry, France

International health professionals will discuss recent findings on Tarlov and meningeal cysts, Arachnoïditis, Cauda Equina syndrome, and neuropathic pain. Patients will share their experience. Translations available in English, French and Spanish.
For further details

14th International Conference on Behçet Disease
Date: 8-10 July 2010
Venue: London, England

Presenting new developments in basic and clinical science to bear on the specific issues of Behçet Disease (BD). Topics to be covered will include immunology of BD, vasculitis in BD, genetic basis of BD, regional inflammation and paediatric BD. The programme will also include debates on topics of current interest or controversy.
For further details

17th International Paediatric Colorectal Club Meeting
Date: 17-19 July 2010
Venue: Padova, Italy

Topics include anomalies of the bowel, anorectal malformation, Hirschsprung disease and urological aspects.
For further details

2th International Congress on Neuromuscular Diseases
Date: 17-22 July 2010
Venue: Naples, Italy

Offering a variety of sessions including paediatric neuromuscular diseases, genetic testing and diagnosis, pathogenic mechanisms of inherited neuropathies, novel therapeutic targets at the neuromuscular junction, motor neuron diseases, and much more.
For further details

International All Star Vasculitis Symposium
Date: 30 July-1 August 2010
Venue: Long Beach, CA, USA

Topics will cover all the vasculitides and will concentrate on the advances in medical treatments, research and quality of life issues for patients.
For further details

FDA Orphan Drug Workshop
Date: 3-4 August 2010
Venue: Minneapolis, Minnesota USA

Over two days, FDA staff from the Office of Orphan Products Development (OOPD) will provide regulatory assistance to sponsors to find regulatory paths forward. Most of the time will be spent in application writing and individual one-on-one guidance sessions to develop the strongest possible orphan designation application to be submitted at the close of the workshop.
For further details

MEN 2010: 12th International Workshop on Multiple Endocrine Neoplasia
Date: 16-18 September 2010
Venue: Viareggio, Italy

This two-day meeting will provide a forum for educating basic and clinical investigators on the most recent advances in the area of hereditary endocrine tumours.
For further details

Second AnEUploidy Workshop
Date: 17-19 September 2010
Venue: Split, Croatia

AnEUploidy is the acronym of an Integrated Project (IP) funded by the European Commission within its Sixth Framework Programme. This project aims to contribute to the understanding of the molecular basis and pathogenic mechanisms of aneuploidies. This second workshop will allow colleagues to share views, advancements, and ideas.
For further details

15th International Congress of World Muscle Society
Date: 12-16 October 2010
Venue: Kumamoto, Japan

The main topics to be addressed include new therapeutic targets for neuromuscular disorders; congenital muscular dystrophies (celebrating the 50th anniversary of Fukuyama congenital muscular dystrophy); and distal myopathies and protein aggregation myopathies.
For further details


Press & Publications

New French language book gives rare disease patients a voice
On the occasion of the third international Rare Disease Day, French national patient organisation l’Alliance Maladies Rares released a publication entitled, "Maladies Rares, Ils Témoignent" (Rare Diseases – Patients’ Testimonies). The book goes behind the statistics to give a voice to the individuals who live each day with a rare disorder - including Marfan syndrome, Addison disease, Friedreich ataxia and others. Published by Editions Le Manuscrit, this French-language book is available from the Alliance Maladies Rares.


Orphanews Europe, the newsletter of the Rare Diseases Task Force
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, Helen Dolk, Anders Fasth, Laura Fregonese, Benjamin Guesdon, 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 Rare Diseases Task Force
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