Task Force Update
Welcome back readers to Orphanews Europe after the summer break !
Welcome also to Kathy Beuzard-Edwards, who is taking over editorship of this Newsletter and Secretariat of the Rare Disease Task Force from Louise Taylor, who left in July to have her second baby. With a background in scientific communication and television journalism, Kathy is also dedicated to this field for personal reasons.
RDTF Expert Group meeting on European Centres of Reference
The second meeting of the Expert Group on Centres of Reference (CR) of the Rare Diseases Task Force took place in Paris on 1 September. The goal was to discuss recommendations to the High Level Group on Health Services and Medical Care regarding a possible European policy in the field of centres of reference for rare diseases (RD). An official report will be published between now and the end of September (see next issue of OrphaNews Europe).
The main conclusions are that very few European countries have established centres of reference for RD, although centres of expertise fulfilling all the criteria to be considered as CR do exist in almost all countries. It would be preferable to consider all expert centres, when establishing a possible cooperation at European level, established either by designation or by reputation and to use the term "Centre of Expertise" rather than "Centre of Reference". The expert group recommends that possible networks of centres of expertise be identified and that networking activities be financially supported in a sustainable manner.
JOB OPPORTUNITIES: Watch this space !
Following our readers’ survey findings, we are currently preparing a “Job Slot” for Orphanews Europe readers interested in recruitment openings in the rare disease field due to appear online this autumn. Announcements will naturally include research positions available for PhD students and post doctoral positions.
If you wish to advertise a post, please contact the : RDTF secretariat
EU Policy News
EU stem cell agreement – no surprises
Replies were mixed to the EU’s stem cell compromise deal in which the Competitiveness Council reached a political agreement, by qualified majority, on the 7th Framework Programme (FP7) for research and technological development (2007-2013). The Council will base its common position on this agreement reached on 24 July before forwarding it for a second reading. Five nations voted against : Austria, Lithuania, Malta, Poland and Slovakia.
The debate took place in public deliberation based on a presidential compromise text focussing on research activities involving human embryonic stem cells under FP7. The agreement clarifies the parameters under which research projects involving human embryos and human embryonic stem cells will be eligible for Community funding.
The Commission also confirmed that it will continue its current practice of not submitting to the Regulatory Committee proposals for projects including research activities which destroy human embryos, including for the procurement of stem cells. However, the exclusion of funding of this research area will not prevent Community funding of subsequent steps involving human embryonic stem cells.
The agreement has provoked criticisms from opposing quarters both for not going far enough, and for crossing ethical boundaries.
Due to the Parliament summer recess, it is as yet unknown how MEPs view the agreement but this will become clear as soon as the FP7 proposal gets its second parliamentary reading in the autumn.
National & International Policy Developments
Bulgaria moves ahead with national RD programme
Bulgaria has a comparatively fast-developing rare diseases policy with both national and regional importance. Since 2004, a free public multilingual information service on rare diseases for patients and medical professionals has been started, operated by a non-governmental non-profit organization in close collaboration and networking with medical and patient associations. As a result, two Eastern European conferences on rare diseases have been successfully organized.
Currently, the new Bulgarian National Health Strategy (2007-2012) is under development. In the draft version of the document from April 2006, an establishment of a Reference Centre for rare and genetic diseases is foreseen (Strategic Aim 6). In addition, an Expert Group at the Bulgarian Ministry of Health was created in July 2006 with the task of creating a National Programme for Rare Diseases (2007-2012).
French Health Ministry's approval of 3rd Centres of Reference list brings total to 103
The French government has issued a new list of nearly 40 additional approved reference centres for rare diseases and groups of rare diseases from all around France. This third wave of approved centres brings the total number of reference centres of this type to 103.
Previous designations of reference centres date from November 2004 and October 2005. Their chief aims are to offer quality of service, draw up recommendations for clinical practice and establish care networks.
Full List of Centres of Reference in France
French national RD call for proposals 2006 : 40 new research projects selected
The results of the French 2006 "Rare Disease" Call for projects launched by the French National Agency for Research (ANR) in association with the French Muscular Dystropy Association (AFM), and managed by the French Institute for Research on Rare Diseases, have just been published.
As is the case each year, the high number of applications (150) concerned a wide variety of high-quality projects. The outcome of a tough evaluation carried out by an Advisory Committee, 40 new research projects were selected. Seven of these are based on rare diseases involving molecular determinants that have not been completely identified.
The increasing number of projects selected from the therapeutic field (28%) is undoubtedly a spin-off of the dynamism started up a few years ago with the creation of the French Institute for Research on Rare Diseases and by the National Plan for Rare Diseases. It is hoped that this activity will be increased even further in 2007, thanks to the support of new research projects to come.
RD News from the Netherlands
The Ministry of Health, Welfare and Sports has assigned the Netherlands Organisation for Health Research and Development (where the Orphan Drugs Steering Committee is accommodated) to write a Research Programme for rare diseases. Research trainee H. Heemstra analysed all health research projects on rare diseases in the Netherlands between 2000 and 2005). The survey will be completed this year. With these results a concept of a specific research programme will be written. Unfortunately, a financial budget (from the Ministry of Health) for such a programme is not foreseen before 2008.
The 8 university hospitals have ample expertise in diagnosis (in which their clinical genetics centres are often heavily involved) and treatment of many rare diseases. Funding of treatment for rare diseases is sometimes problematic, as hospitals are not always refunded for treatment provided. Therefore, expert centres for rare diseases in university hospitals are not very stable and may easily disappear because of financial difficulties.
A new initiative in the Netherlands to establish the Dutch umbrella organisation for university hospitals (NFU) will be launched this month. This organisation will draw up an inventory on RD expertise in the 8 university hospitals using a list with more than 1000 rare diseases. This list is composed by a special committee that advised the Ministry of Health, Welfare and Sports about deduction for national insurance especially in the case of rare diseases. This committee made an inventory about the need for care, possibilities for treatment and future costs. University hospitals will add their experience on research, care and treatment on this list. The NFU's inventory will provide sound information on the expertise of each university hospital for the various rare diseases.
Next to the 8 university hospitals there are also special Healthcare and Treatment Centres for several diseases in other hospitals, where in some cases fundamental and applied medical research is also being performed.
Other European news
Belgian cell culture plant announces major expansion: good news for European orphan drugs development
Genzyme Corporation has announced it is to expand its manufacturing capacity at Geel to step up its production of Myozyme® (alglucosidase alfa), an enzyme replacement therapy treatment and first approved drug for Pompe Disease.
Pompe’s disease is a juvenile disease which sets in before the age of three months and proves fatal before the child is two years old. Myozyme has been approved in Europe for Pompe Disease treatment since 29 August 2006.
Myozyme is currently produced at two of Genzyme’s U.S. production sites. Myozyme was first approved in the EU in March this year and subsequently in the US and Canada. With this third production plant, the corporation is now seeking both to register the treatment worldwide as well as keep ahead of growing demand.
See Also "New Books" for new literature on Pompe Disease.
Spain's First Rare Disease Week : 21-27 October 2006
Spain is holding its first Rare Disease Week from 21 to 27 October this year. Activities forming part of a nationwide awareness campaign and event will take place in Madrid, Seville, Badajoz, Alicante and Barcelona, coordinated by the Rare Disease Research Foundation FEDER (in Spanish only).
For details of the 7th EPPOSI Workshop held as part of Rare Diseases Week in Madrid on 26-27 October, go to What's On Where in October ?
Other international news
“European PubMed Central” Initiative for Biomedical Open Access Archive
The creation of a free, open access worldwide library of biomedical research is the subject of current talks between the UK’s largest biomedical research charity, the Wellcome Trust, and the US National Library of Medicine.
The idea is to establish an international database of peer-reviewed, biomedical research with free access for all : a kind of European-based Pub-Med Central.
This proposal has been shaped by two reports commissioned by the Wellcome Trust into scientific publishing. It comes at a time of growing concern over the way in which scientific findings are published, the subject of a recent enquiry by the UK’s House of Commons Science & Technology Committee.
Research in Action
Practical Genetics: European Journal of Human Genetics & Orphanet partnership
The European Journal of Human Genetics, in partnership with Orphanet, has just published its first two articles in a series entitled “Practical Genetics” with open access and free downloading. The September 2006 issue of the EJGH features an article on the Rubinstein-Taybi Syndrome whilst last month’s journal highlighted a paper on new clinical and molecular insights of Rett Syndrome.
Future issues will include articles on the following subjects: Proteus Syndrome, Joubert Syndrome, Sotos Syndrome, Tuberous Sclerosis, Neurofibromatosis, Börjeson-Forssman-Lehman Syndrome and the otopalatodigital syndrome spectrum disorders.
New diseases & syndromes
Macrostomia - preauricular tags - external ophthalmoplegia
A new syndrome, characterised by macrostomia or abnormal mouth contour, preauricular tags, and uni- or bilateral ptosis, has been described in nine members of a Brazilian family. It is a new phenotype within the oculo-auriculovertebral syndrome, with an autosomal dominant transmission.
Cleft Plate Craniofacial Journal; 43(4): 429-434; July 2006
Congenital malabsorptive diarrhea
Congenital malabsorptive diarrhea is characterised by generalised malabsorption and a paucity of enteroendocrine cells. It is caused by homozygous loss-of-function mutations in the NEUROG3 gene, coding for neurogenin-3.
NEJM;355: 270-280; July 20, 2006
PELVIS is an acronym displaying the association of perineal hemangioma, external genitalia malformations, lipomyelingomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag, in this syndrome. 11 cases have been described.
Archives of Dermatology; 142 : 884-888; July 2006
Leukoencephalopathy with metaphyseal chondrodysplasia
Leukoencephalopathy with metaphyseal chondrodysplasia, X-linked transmitted, has been observed in four males belonging to a three-generation family. The causative gene may be located on Xq25-q27.
Neurology; 67:587-591; August 22, 2006
New rare disease genes published on PubMed
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia
MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients
Mutations of human TMHS cause recessively inherited non-syndromic hearing loss
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus
Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection
X linked cone-rod dystrophy, CORDX3, is caused by a mutation in the CACNA1F gene
A New Autosomal Recessive Form of Stickler Syndrome Is Caused by a Mutation in the COL9A1 Gene
Navajo Neurohepatopathy Is Caused by a Mutation in the MPV17 Gene
Mutations in the CEP290 (NPHP6) Gene Are a Frequent Cause of Leber Congenital Amaurosis
Peters Plus Syndrome Is Caused by Mutations in B3GALTL, a Putative Glycosyltransferase
Mutations in the Gene KCNV2 Encoding a Voltage-Gated Potassium Channel Subunit Cause "Cone Dystrophy with Supernormal Rod Electroretinogram" in Humans
New fundamental research
New fundamental research published on PubMed
Anti-Interferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1
Antisense oligonucleotide therapy for neurodegenerative disease
Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin
New clinical research
New clinical research published on PubMed
The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome
At risk for Huntington disease: The PHAROS (Prospective Huntington At Risk Observational Study) cohort enrolled
Saccades in presymptomatic and early stages of Huntington disease
Validity and clinical applicability of the acromegaly quality of life questionnaire, AcroQoL: a 6-month prospective study
Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition
Multifocal motor neuropathy with and without conduction block: a single entity?
Slower disease progression and prolonged survival in contemporary patients with amyotrophic lateral sclerosis: is the natural history of amyotrophic lateral sclerosis changing?
New clinical trials & tests registered with Orphanet
Efficacy of tranexamic acid on Rendu-Osler epistaxis. A randomized trial on beneficial and iatrogenic effects.
Clinical Trial Comparing Treatment of Relapsing-Remitting Multiple Sclerosis (RR-MS) with Two Doses of Glatiramer Acetate (GA)
The following clinical study is recruiting patients until the end of November 2007 :
Genotype phenotype study of mutations in the Wnt7a gene causing FFU syndrome and Schinzel Phocomelia (Fuhrmann syndrome, Limb pelvis hypoplasia-aplasia syndrome, Al-Awadi-Raas-Rothchild syndrome).
New clinical test results
Auris Medical reports results of a phase I/II clinical trial with AM-111.
CICERO: An innovative information-sharing system for rare haematological diseases
Launched as a pilot scheme in May this year, CICERO (Collection of Investigational Case reports – an Electronic Registry of Outcomes) is a non-profit online registry of case-treatment episodes. Diseases initially dealt with are a subset of rare haematological conditions including lymphoma, myeloma, CLL & auto-immune haematological diseases. The system enables efficient and low-cost online publication and sharing of important clinical outcome data, carefully targeting rare diseases or rare clinical scenarios where no standard treatment yet exists.
The service avoids positive outcome publication bias by way of an efficient pre-publication approval system. This is made possible by a preliminary submission process basing itself on the agreement between clinician and patient to start investigation through treatment. Approval is only given if the contributor agrees to supply follow-up outcome data (not only positive, but also negative or neutral).
The project is unusual in that it takes into account adverse event data and quality of life measurements, rather than just effectiveness data. Further incentives to participate exist in the form of a small financial reward for participating patients. The project is currently supported by charitable donations from individuals and drugs companies with finances strictly controlled by a NHS UK registered charity.
Once the pilot stage is over, CICERO intends to look beyond haematology to other rare diseases. The team working on this registry is confident that it will not compete with clinical trials and recruitment in rare diseases. It is confident that the databases will prove to be complementary to trials as they expect to be freely consulted in order to obtain crude outcome rates as well as crude duration responses which will, in turn, help inform clinical trial design in this still relatively uncharted territory.
CICERO organisers would be interested to hear from readers with suggestions (contact) to improve, support or expand the service to other specialised areas.
Orphan drug research
New designations & authorisations in Europe
New indications authorised for Glivec
has just adopted a positive opinion for two extensions of indications by Glivec (inatimib) :
the treatment of protuberant dermatofibrosarcoma
adult treatment of severe Philadelphia positive lymphoblastic leukemia
Glivec is already authorised in Europe for the treatment of chronic Philadephia positive myeloid leukemia as well as adult treatment of Kit positive non-resecable and/or metastatic stromal gastro-intestinal tumours.
To read more about "Dermatofibrosarcoma protuberans"
Severe active Crohn Disease : change of indication for Remicade
EMEA has recently adopted a positive opinion for a change of indication for Remicade (infliximab) in the treatment of Crohn Disease. Remicade will be indicated as a second-line treatment (rather than a third-line treatment as is currently the case) for this pathology.
EMEA press release ; 4 August 2006
To read more about "Noonan syndrome"
Six new orphan drug designations in July 2006
Last July the COMP (Committee for Orphan Medicinal Products) awarded an orphan designation to six medicinal substances for the following indications :
Treatment of pancreatic cancer
Treatment of Duchenne muscular dystrophy
Treatment of glioma
Treatment of pulmonary infections by Pseudomonas aeruginosa in cystic fibrosis
Treatment of cancers of the billiary tract
Treatment of acute myeloid leukemia
Details of all orphan designations and authorisations granted to date by the European Commission are entered in the European Community Register of Orphan medicinal products.
New designations & authorisations in USA
Hunter Disease : FDA approval for Elaprase
Hunter Disease (or mucopolysaccharidosis type II) is a lysosomal disease due to iduronate-2-sulfatase deficiency with growth retardation, facial dysmorphism and articular limitations. Patients most severely affected also suffer from cardiac and respiratory problems, hepatosplenomegaly and neurological deficiency. The Food and Drug Administration has just authorised the commercialisation of idursulfatase, a human recombinant iduronate-2-sulfatase bearing the market name of Elaprase, for the treatment of this disease. Elaprase, which was submitted simultaneously by Shire to the FDA and the EMEA has been designated by the EMEA as an orphan drug for the same indications. The EMEA is expected to come to a decision regarding the drug's commercialisation in Europe.
A clinical phase II/III test has shown that a weekly administration of idursalfatase significantly improves the patient's ability to walk. However, the substance may lead to acute hypersensitive reactions, necessitating appropriate medical follow-up during the treatment.
Genetics in Medicine ; 8(8) : 465-473 ; August 2006
FDA Press Release ; 24 July 2006
To read more about "Mucopolysaccharidosis type 2"
Ethical, Legal & Social Issues
Genetic testing on the Web has arrived: where to now ?
Genetic testing & laboratory services marketing direct to the customer is upon us, according to an article published in the New England Medical Journal. Consumers armed with a computer and a credit card are now just a few clicks away from ordering a test such as that necessary for the BRCA1 or BRCA2 gene mutation or indeed any of several hundred diagnostic assays – irrespective of their doctor or health insurance cover.
Universal access to genetic information for all is progressively becoming a reality but with it comes widespread questioning of the ethics involved. Gene diagnostic companies and clinical geneticists argue that these tests bring sophisticated diagnostic services to consumers interested in genetic testing, able to afford the process but lacking access to clinical testing sites. The anonymity assured by such testing to customers fearing discrimination by employers or by insurance companies is a major argument used by the pro genetic testing lobby.
The author argues that since the companies involved are driven by largely commercial interests they can exploit anxious users by selling them tests they don't actually need. Lack of follow-up counselling is also a worry since many users need this in order fully to understand the test results.
A further concern is which party should take on the main ethical responsibility in this situation. The ethical questions raised by the dilemma of test results disclosure can be a source of conflict between patient and doctor, as doctors can find themselves regarded as an accomplice in an act of fraud, whilst patients may be considered ineligible for life insurance or disability insurance.
Dr Wolfberg was one of the first medical professionals to write about these genes testing developments in an international journal and thereby open up a public debate on the issue. He is a Fellow at the maternal foetal medicine department at Tuft's-New England Medical Centre, Boston, USA.
Courses & Educational Initiatives
Diploma in Down Syndrome in Canada
A diploma in Down Syndrome resulting from a collaboration between Simon Fraser University in British Columbia, Canada and the Down Syndrome Research Foundation looks set to materialise this autumn when the course goes online.
The programme will consist of 3 online courses over a period of 8 months starting in September 2006, adopting an individual rather than disability-focussed approach. It will particularly target parents and closely involved professionals working or wishing to work with children and/or adults with Down syndrome, but it will also be of interest to professionals in any disability field.
It is expected that the course’s links with Simon Fraser University will lead to the diploma being recognised for university credit. A pilot run of the first course will be offered at an initial reduced price in September 2006. Further information can be obtained at: Contact
Press & Publications
Neural Tube Defects – from origin to treatment
Author: Carys M. Bannister
Publisher: Oxford University Press, 2006
Fanconi Anemia: a paradigmatic disease for the understanding of cancer and aging
Due to be published as a volume in the series: Monographs in Human Genetics
Collected authors edited by : Detlev Schindler, Holger Hoehn
Publisher : Karger, 2006
Obesity and Genetics: a public health perspective
CDC Office of Genomics and Disease Prevention & the Division of Nutrition and Physical Activity at CDC’s National Center for Chronic Disease Prevention & Health Promotion
Author: Geeta Anand
Publisher: HarperCollins August 2006
A portrayal of challenges faced by patients and families struggling with Pompe disease, also describing efforts by physicians, patient associations and companies involved in Pompe research, by Wall Street Journal & Pulitzer prize-winning journalist Geeta Anand, known for her coverage of biotech issues.
The Path from Genome-based Research to Population Health : development of an international public health genomics network
Authors: Wylie Burke, Muin J. Khoury, Alison Stewart & Ronald L. Zimmern
Genetics in Medicine : July 2006 vol. 8 no. 7
A Journey of Hope: lessons learned from studies on rare diseases and orphan drugs
Authors: Wastfelt M, Fadeel B., Henter J.I.
Publisher: PubMed-Medline, 2006
The Common Problem of Rare Disease in General Practice
Author: Knight A.W.
Publisher: PubMed-Medline, 2006
What's on where?
Rare Diseases & Orphan Drugs Events Week – Rome, Italy
An International Meeting on Rare Diseases and Orphan Drugs
Date : 18-19 September
Venue : Istituto Superiore di Sanità (ISS) Rome
The Meeting will highlight important health and research projects from different countries, as well as EC-supported actions followed by
The NEPHIRD Conference
Date : 20-23 September, same venue
The Conference is organized as part of the Network of Public Health Institutions on Rare Diseases (NEPHIRD) & funded by DG-SANCO.
These events will bring together researchers, health professionals, patient associations, health policy experts, industry & will address problems and possible solutions from research to quality of life of people living with rare diseases.
British Society for Human Genetics Annual Conference
Forum for people working in human & medical genetics.
Date : 18-20 September 2006
Venue : York University, UK
2nd National Congress of Medical Genetics (with international participation)
Date : 20-23 September 2006
Venue : University of Medicine and Pharmacy, Cluj-Napoca, Romania.
This event will be preceded by a Post-graduate course, approved by the College of Doctors 19-20 September on “The Impact
of Medical Genetics in Human Pathology"
International Conference on Chromosome 14 Deletion
1st International Conference by the Italian Ring 14 Association
Date : 13-14 October 2006
Venue : Hotel Mercure Astoria, Reggio Emilia, Italy
International Conference on genomics
"Genomics for Health", organised by the Austrian genome research programme GEN-AU, will deal with scientific research, ethical, industrial as well as legal aspects, focussing on : metabolic diseases, oncology & systems biology.
Date: 15-18 October 2006
Venue: Hotel Intercontinental, Vienna, Austria
7th EPPOSI Workshop: “Positioning Rare Diseases on the Healthcare Agenda” & Spain's Rare Diseases Week
This major event in the rare disease community's calendar will bring together representatives from key stakeholder groups – patients, regulators, charities, the academic and clinical community, industry and health care providers to discuss the issues involved in positioning rare diseases on the healthcare agenda.
This year’s Workshop will provide the opportunity to evaluate 5 years experience of the European Regulation on Orphan Medicinal Products. We hope the Workshop will boost further practical and successful application of this regulation. The sessions will be organized around the following questions:
* How to enable the appropriate assessment of new therapies?
* How to assess the benefit of therapies for patients and their families?
* How to enable the development of orphan indications of marketed drugs?
* How to ensure optimal access to treatment?
EPPOSI's aim is to provide a platform for the cultivation of partnerships between industry, patients, academia, together with European authorities, so as to convert policy issues and scientific developments into therapies for rare diseases.
All Workshop sessions will feature high-level speakers and experts, representing the different EPPOSI parties and stakeholders. This year’s Workshop will be the second with an international scope, not only bringing together European authorities and stakeholders, but also uniting the support of both the National Institutes of Health (NIH) and the Food & Drug Administration’s (FDA) Office for Rare diseases.
This event follows six successful EPPOSI Workshops in the Federal Parliament in Brussels in September 2000, the French Senate in Paris in October 2001, the Chamber of Deputies of the Italian Parliament in Rome in 2002, and three hosted by ministries in The Hague (2003), Berlin (2004) and London (2005).
Date: 26-27 October, 2006
Venue: IMSERSO, Spanish Ministry of Labour and Social Services, Madrid, Spain
ORPHANEWS EUROPE will be bringing you a full report on the highlights of this major international event in the rare diseases field.
For details of Spain's first Rare Disease Week (21 to 27 October) this year, go to Other European News
XIIth meeting of the European Society for Immunodeficiencies
Date: 4-7 October 2006
Venue: Budapest, Hungary
ELA Foundation Congress : the vital function of myelin development and maintenance
Date: 5-7 October 2006
Consult the programme
17th International Symposium on the Autonomic Nervous System
Date: 1-4 November 2006
Venue: Rio Grande, Puerto Rico
Symposium on Orphan Drugs in Belgium
This European symposium aims to evaluate and compare orphan drugs in Belgium with those of France & the Netherlands and is addressed at all those directly concerned, from patients & carers, to researchers, pharmacists, governmental authorities, politicians, etc.
Date : 7 December 2006
Venue : Belgium Federal Parliament, Brussels, Belgium
International Congress for Genetics in Paediatrics
Date: 24-27 January
Venue: Merridien-Sonesta Hotel, Luxor, Egypt