17 November 2010 print
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Editorial
 
Belgium and the Czech Republic advance their national rare disease strategies
 


On 9 June, 2009, the European Council adopted the Recommendation on an Action in the Field of Rare Diseases, calling on each European Union (EU) Member State (MS) to elaborate and adopt a strategy for their rare disease patients by the end of 2013. The Council Recommendation defines seven strategic areas for rare disease care, of which the first - Plans and strategies in the field of rare diseases – urges the MS to develop actions that encompass the elements of the following strategic areas: Adequate definition, codification and inventorying of rare diseases; Research; Centres of expertise and European reference networks; Gathering expertise on rare diseases at European level; Empowerment of patient organisations; and Sustainability.

In October, the Czech Republic released a ten-year strategy for its rare disease patients, estimated to be roughly 20,000 in the country of 10.5 million habitants. The Czech strategy, “intended to ensure the effective diagnosis and treatment of rare diseases, ensure that all patients with rare diseases have access to the indicated, high-quality health care, and ensure their subsequent social integration on the basis of equal treatment and solidarity”, is “fully compliant with the European Council's recommendation mainly concerning improved identification of rare diseases, support for the development of health policy and the development of European-level cooperation, coordination and regulation in this field”. The Strategy outlines existing efforts and proposes major targets and measures for improving the situation in the Czech Republic, which are to be subsequently specified in more detail in the context of a three-year National action plan that will establish “sub-tasks, instruments, responsibilities, dates and indicators for fulfilling individual tasks”. The first meeting of the working party for the preparation of the National action plan was scheduled to convene on 12 November in Prague. The Czech ten-year strategy, available on the European Commission’s Public Health Rare Diseases website, reveals the budgetary sources for the plan, which will include “existing budgetary chapters and domestic and foreign subsidies” such as the Ministry of Health and the country’s public health insurance. Consult the Czech Republic ten year rare disease strategy

The Czech Republic is not alone in its effort to develop a rare disease strategy. In February 2009, the Belgian House of Representatives adopted a resolution for a plan of action for rare diseases and orphan drugs. The Rare Diseases and Orphan Drugs Fund, managed by the Fondation Roi Baudouin, was mandated to coordinate the elaboration of a Belgian rare disease plan. Patient representatives, physicians and other specialists, paramedical staff, insurance organisms, social service representatives, members of industry, and political authorities participated in the working groups that developed a set of recommendations which groups specific measures into four central domains: diagnostics and treatment; codification and inventory; information, awareness, and patient empowerment; and access and cost. Under these four areas come a series of proposed measures that include the creation of centres of expertise/coordination; the establishment of a national platform; the development of a national registry; the creation of a national information portal; support for Orphanet Belgium; the modification of existing legislation to allow reimbursement of DNA samples tested abroad; a coordinated approach to non-DNA testing; establishment of a mechanism for the early access (pre-marketing authorisation) and reimbursement of orphan drugs (similar to the system currently used in France); establishment of an inventory of off-label product use; assurance that primary materials for treating rare diseases can be used legally; the modification of existing criteria used to confer an orphan designation when a suitable primary material is available and utilised; and support and monitoring for orphan drug use in the home setting. It is anticipated that the Belgian plan, to be unfurled in phases, would generate costs between 9 and 30 million Euros per year over a five-year period for the Belgian health insurance system. While Belgium continues to establish its new government, work on the second phase of the strategy is nonetheless progressing with further defined recommendations in the areas of non-medical costs of rare diseases, international networking, research, adherence, advanced therapy medicinal products (ATMP), ethical issues, teaching and education, therapeutic education, and clinical trials.
Consult the Belgian rare disease strategy recommendations (in French language).
Visit the European Commission Public Health Rare Diseases webpage for national strategies
 


 
EU Policy News
 
European Union and the USA on track to cooperate on research into rare diseases
 
The European Commission (EC) and the USA’s National Institutes of Health (NIH) held a joint workshop in Reykjavik, Iceland, on 27-28 October, to discuss ways in which to foster transatlantic cooperation on research into rare diseases. This workshop was the first step of a process through which the EC and the NIH hope to establish an ambitious international research programme to speed up the development of diagnostic and therapeutic solutions for patients. This programme is intended to be open to other countries, in order to be truly International and not simply bilateral. Its principle was drafted a few months ago when Dr Ruxandra Draghia-Akli (Director of the Health Directorate at the EC’s Research DG) and Dr Francis Collins (NIH Director) met to discuss the possibility of bilateral cooperation.

The Icelandic workshop gathered 40 participants from the EC and the NIH administrations, as well as representatives from patient organisations, the biopharmaceutical industry, and academia. The discussions allowed a review the successful initiatives already taken on both sides of the Atlantic, and an exploration of what could be developed in common to speed up R&D. Currently, EU and US calls for research proposals are open to transatlantic cooperation, but it would more advantageous to have a single Joint Call, as has been demonstrated by previous joint programmes such as the International Knock-out Mouse Consortium, the Human Metagenome Consortium, the Cancer Genomics Consortium and the Epigenomic Consortium, among others.



This International programme needs to have ambitious goals, and must establish common policies and define shared resources, such as common Standard Operating Procedures, ontologies and data quality controls. It should ensure fair sharing of the workload and avoid funding overlap. Overall, it has to create a dynamic. The Reykjavik workshop was intended as a brain-storming session to review areas for cooperation which will serve to draft the outline of a future programme, to be further delineated at a workshop scheduled to be held in Washington in April 2011, where decisions will be taken. The first area which was discussed in depth in Iceland, was the existing hurdles in the field of clinical research, specifically the lack of good clinical data on many diseases. The field of patient registries tops the list of areas to improve, including the constitution of repositories of data, data format and outcome variables (such as those of the PhenXtoolkit), templates for writing research protocols, informed consent forms, and rules on data sharing. This field requires a public-private partnership, since, in any case, patient data must be collected when a product is marketed. Good practice guidelines to share and access data need to be established and widely distributed. The factors of success and of failure during the R&D process were analyzed both by European Medicines Agency and US Food and Drug Administration representatives. Most discussed were ways to decrease the failure rate (currently 85% after Orphan Drug Designation) as a means to both increase the number of marketed products and to decrease the cost of individual products. The example of the Rare Disease Repurposing Database was cited as an example. The issue of training was also discussed at length, particularly as it pertains to Small- and Medium-sized Enterprises and to the training of young clinicians who are not well enough informed of the regulatory aspects of clinical research. Industry representatives presented a concept currently under discussion between members of the group of research directors at the European Federation of Pharmaceutical Industries and Associations (EFPIA), named the “Cookie Jar”, into which each company could put promising products that they do not want or cannot develop, for another company to develop, with the condition that the other company also puts products into the Cookie Jar, to balance the benefits. This idea was thought very promising in order to ensure no waste of opportunities for patients. The ERDITI initiative was also presented as an example of good practice. This lead to a recommendation to push forward the Creative Commons concept as the right framework for the management of many platforms, seen as pre-competitive, as the only way to de-risk the R&D process, to both decrease costs and optimise the success of the R&D process.

The avalanche of new scientific data coming from the whole genome sequencing approach was also discussed as very promising for patients, many more of whom who will be able to receive a diagnosis for their condition, and also positive for researchers and clinicians who will be able to better understand the underlying mechanisms. However, the changing situation requires a new approach as the tools to handle and interpret massive data do not yet exist. The proposal to establish a Human Phenome Consortium was made, which would include the current effort of the Human Variome project, the ontologisation of various human disease databases to allow their interconnection with other biological ontologies, including the Mouse phenome ontology, and the establishment of an international nomenclature of clinical physical and functional anomalies, the development of multi-terminology servers and the implementation of a nomenclature of rare diseases in health information systems.

Participants were well aware of the difficulties to be faced in the current economic context. The setting up of this ambitious programme requires commitment of the Community of researchers and of the funding agencies. It will be a challenge to implement, to agree on its governance, to convince the Community that, if “Big is bad” and “Small is beautiful”, combining both is the best approach. The physicists were able to establish their enormous international research programmes - so why not the Rare Disease research community? Let’s go for it!

 
New pre-implantation genetic diagnosis technology guidelines from the European Society of Human Reproduction and Embryology
 
The European Society of Human Reproduction and Embryology (ESHRE) has issued four separate guidelines – one of which delineates the organisation of a Pre-implantation Genetics Diagnosis (PGD) centre, while the remaining three concern the various testing methods - amplification-based testing, fluorescence in situ hybridisation (FISH)-based testing and polar body/embryo biopsy. In a press release, the guidelines, updated from 2005 and published in the journal Human Reproduction, are described as “…a set which, taken together, form a complete best-practice compendium”. In the first guideline, the authors identify the basic requirements for an IVF/PGD centre, and discuss patient inclusion/exclusion criteria, accreditation, genetic counselling and transport PGD (when patients are treated at one IVF centre, while their gametes/embryos are tested elsewhere, at an independent PGD centre). The three other guidelines focus on technical requirements for the laboratory, clinical protocols, and post-diagnosis follow-up for the specific testing method. Quality control and assurance are addressed. The press release indicates that recommendations for controversial pre-implantation genetic screening (PGS) are also included in order to “…assist every professional in the reproductive field to develop the best laboratory and clinical practice possible”.
 


 
National & International Policy Developments
 
New report evokes the “challenge of rarity” in England’s health care system
 
England’s Specialised Healthcare Alliance (SHCA) describes itself as “a broad coalition of patient groups supported by a smaller number of corporate members” that was formed in 2003 specifically to lobby for rare disease patients and those with other complex illnesses that need specialised, frequently expensive, medical care. The SHCA has issued an overview and critique of England’s new arrangements for health service commissioning for small patient populations and has developed recommendations to enhance the approach to cost assessment of treatments for these patients. A discussion of the ethical framework that has been introduced to the assessment process for determining cost effectiveness is provided. The Coalition Government is consulting about a number of aspects of how the NHS in England will work, including the future of the proposed Innovation Pass (see OrphaNews Europe 23 December 2009) that would allow funding of orphan products for a period of up to three years pending their appraisal. Consult the SHCA report
 
President Obama signs into law act that improves access to rare disease clinical trials
 
In October, US President Barack Obama signed into law S. 1674, the Improving Access to Clinical Trials Act. The measure amends the current Social Security Act by providing an exclusion for compensation provided to individuals participating in clinical trials for rare conditions. Previously, the loss of supplemental Social Security or Medicaid benefits for potential trial candidates who were offered compensation for trial participation hampered participation. Consult law S.1674
 
Other European news
 
First three babies born in Europe following use of novel chromosomal IVF screening procedure
 
A set of twins in Germany and another baby in Italy were born following comparative genomic hybridisation (CGH) by microarray – a novel method that screens in vitro fertilisation oocytes for “a full range of chromosomal disorders.” The pilot study sought to “determine the clinical value of CGH as a non-subjective means of genetic screening before embryo transfer”. The three births, along with several pregnancies that are ongoing, are “the final stage in the ‘proof of principle’ that the screening of oocytes and embryos before transfer in IVF can increase birth rates; both these pregnancies were derived from oocytes whose complete chromosomal status had been assessed by microarray CGH”. Many failed IVF efforts are due to chromosomal abnormalities. Benefits to the new procedure include the skirting of laws in countries that forbid embryo analysis and freezing, since the screening is conducted on oocytes, and the reduction of multiple pregnancies by single embryo transfer. The procedure could particularly be useful to women aged 37 and older. Learn more
 


 
Ethical, Legal & Social Issues
 

 
Calling Doctor Google – the public use of internet for obtaining rare disease diagnostic information
 
A new paper published in Archives of Disease in Childhood presents the cases of two sets of Dutch parents who successfully identified lysosomal disease diagnoses for their children via information found on the internet. Both parents were able to communicate their findings to their respective health professionals, who then administered the appropriate tests to confirm diagnosis. The authors elicit the “utility of publicly available internet search engines in diagnosing rare disorders.” Furthermore, the authors evoke the “lengthy diagnostic odyssey” that many rare disease patients and their families endure, a process that is even “more devastating if an early diagnosis is of vital importance for the efficacy of treatment”.
Read the PubMed abstract

 
A qualitative study describes the experience of parents living without a diagnosis
 
A study published in Genetic Testing and Molecular Biomarkers describes a series of interviews with parents who do not have a diagnosis for their ill child. The study evokes the emotional and sociological experiences that such parents undergo. Paradoxically, while parents confirmed that they would prefer to have a diagnosis “…when probed further, many said that getting a diagnosis was no longer a priority. This was either because they were more concerned with dealing with the day-to-day issues related to the condition, they felt that their child was happy, and therefore, a diagnosis was not vital, or they had come to accept their child’s condition and wanted to move on”. This said, the study found that while there are many commonalities between families with a diagnosed child and those with an undiagnosed child, “lack of diagnosis adds a layer of complexity”. The authors report that some 30%–50% of cases of children with severe learning disability and 60% of cases of children with multiple congenital anomalies are undiagnosed. Consult the PubMed abstract
 
Norwegian study depicts the difficulty women face in deciding whether to terminate an affected pregnancy
 
An article published on the Norwegian Information Centre for Gender Research website describes the painful process women undergo in deciding whether or not to terminate a pregnancy affected by a genetic or chromosomal abnormality, particularly when detected in the second or third trimester of a woman’s pregnancy. At the Limit of What a Person Can Bear presents the subjective experience of Norwegian women who underwent prenatal diagnostics and consequently were offered selective abortion. The article contrasts the decision-making process between women with a foetus affected by serious, often fatal anomalies and those with less severe conditions, such as trisomy 21 or Klinefelter syndrome. Both scenarios carry their own complex factors that can render the decision-making process difficult. The author educes the “paradox within society” that both condemns and encourages the termination of affected pregnancies, and the impact this paradox has on the woman left alone to decide. Learn more
 


 
EU Project Follow-up
 

 
GenTEE project captures genetic testing activity in emerging economies
 
The three-year CAPABILITY project was developed jointly by units three (Clinical Genetics, Community Genetics and Public Health) and six (Education) of the Network of Excellence EuroGentest in collaboration with leading experts from Argentina, Egypt and South Africa. The project’s main objective is to “contribute to the efforts to establish and sustain a worldwide harmonisation process for quality standards for the integration of genetic test/genomic knowledge applications into practice and prevention and to serve as a model project for successful, sustainable collaboration between EU research centres and centres from developing countries”. Several papers have been published by the project participants, including current situation and needs assessment reports for genetic testing services in Argentina, Egypt, and, most recently, South Africa. The report Genetic Testing in Emerging Economies An International Pilot Study Preliminary Report on South Africa has been made available on the website of the European Society of Human Genetics (ESHG). The report captures the current situation for genetic testing in South Africa, offering a comprehensive snapshot of the information available on the prevalence of genetic/congenital disorders and a list of available genetic services in the country. As of 2008, there were five genetic service facilities in South Africa. The report discusses the genetic services offered, and the corresponding reimbursement policies in the country. Barriers to genetic services (financial, geographic, et cetera) are also discussed. Consult the document
 
Communicating risk: a new online tutorial for health professionals in prenatal diagnostics
 
Research groups from Italy, Switzerland, Poland and France have developed a web-based tutorial geared to help health professionals communicate probability risks related to pregnancy to patients undergoing prenatal diagnostics. Available in English and Italian languages, the freely available tutorial guides the user through four interactive units designed to help health professionals portray specific risks as accurately as possible: Numerical Techniques; Verbal Labels and Comparison Scenario Techniques; Mental Imagery Techniques and the Framing Effect; and Graphic Techniques. The tutorial has been developed with the financial support of the European Commission (Special Advances in Foetal and Neo-Natal Evaluation Network (SAFE) Project N: LSHB-CT-2004-503243). Consult the free online risk communication tutorial
 


 
Orphanet News
 
Mick Jagger had it wrong …. you CAN get satisfaction (ask the readers of the OrphaNews Europe survey)
 

The editorial team of OrphaNews Europe was tremendously pleased to learn that the overwhelming majority of readers who responded to the Reader Satisfaction Survey that was conducted this summer reported being either “satisfied” or “very satisfied” with the contents and quality of the newsletter. Never ones to rest on our laurels, however, OrphaNews Europe, the official newsletter of the European Union Committee of Experts on Rare Diseases (formerly the European Commission’s Rare Diseases Task Force), has taken stock of the improvements readers would like to see. These include a search engine for sifting through the archives of the newsletter, the possibility to build a customised letter that targets the specific items of interest to an individual reader, an RSS Feed providing punctual updates, and a desire for more collaboration with rare disease experts on the other side of the Atlantic and in other areas. Plans are already underway to develop these features, most of which should become available in 2011. OrphaNews Europe thanks the 1077 readers hailing from over 50 different countries who took the time to reply to the survey, and who represent a wide variety of professions and interests – including scientists and researchers, members of the biopharmaceutical industry, government representatives, and patients, families, and patient organisation members. Medical professionals accounted for the majority of readers who replied – almost 50%. The survey also revealed that amongst the sections most frequently read are the new syndromes, new genes, orphan drug news, and political and national/international news sections. The calendar of upcoming events was also cited as being regularly consulted, along with new publications. The survey results provide the OrphaNews Europe team with a compass, pointing toward the directions the majority of readers would like to see the newsletter take. We're on our way. Consult the OrphaNews Europe Reader Satisfaction Survey

 
New Texts
 
New Orphanet Journal of Rare Diseases publication
 
Dent's disease
 


 
New Syndromes
 

 
A new syndrome of mandibular hypoplasia, deafness, and progeroid features with lipodystrophy and undescended testes
 
The authors report seven patients with mandibular hypoplasia, deafness, progeroid features, and associated lipodystrophy. These patients have similar features to mandibuloacral dysplasia patients such as hypoplastic mandible, beaked nose, stiff joints, and sclerodermatous skin. However, the patients did not harbour any disease causing variants in LMNA or ZMPSTE24 and showed distinct characteristics such as sensorineural hearing loss and absence of clavicular hypoplasia and acroosteolysis. All males with MDP had undescended testes and were hypogonadal. The molecular basis of this new entity remains to be elucidated.
Read the PubMed abstract

 
J Clin Endocrinol Metab ; E192-197 ; October 2010
 


 
New Genes
 

 
Congenital stationary night blindness: SLC24A1 implicated in autosomal-recessive form
 
Read the PubMed abstract
 
To read more about "Congenital stationary night blindness"

 
Am J Hum Genet ; 523-531 ; 8 October 2010
 
Cone-rod dystrophy: mutations in PCDH21 cause autosomal recessive form
 
Read the PubMed abstract
 
To read more about "Cone rod dystrophy"

 
J Med Genet ; 665-669 ; October 2010
 
Charcot-Marie-Tooth disease: compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient
 
Read the PubMed abstract
 
To read more about "Charcot-Marie-Tooth disease"

 
Am J Hum Genet ; 560-566 ; 8 October 2010
 
Van Den Ende-Gupta syndrome: mutations in SCARF2 are responsible
 
Read the PubMed abstract
 
To read more about "Van den Ende-Gupta syndrome"

 
Am J Hum Genet ; 553-559 ; 8 October 2010
 
Diaphanospondylodysostosis: BMPER mutation identified
 
Read the PubMed abstract
 
To read more about "Diaphanospondylodysostosis"

 
Am J Hum Genet ; 532-537 ; 8 October 2010
 
Hereditary sensory and autonomic neuropathy type 1: mutations in the SPTLC2 subunit of serine palmitoyltransferase at cause
 
Read the PubMed abstract
 
To read more about "Hereditary sensory and autonomic neuropathy type 1"

 
Am J Hum Genet ; 513-522 ; 8 October 2010
 
Kallmann syndrome: WDR11, a WD protein that interacts with transcription factor EMX1, is mutated
 
Read the PubMed abstract
 
To read more about "Kallmann syndrome"

 
Am J Hum Genet ; 465-479 ; 8 October 2010
 


 
Research in Action
 

 
Fundamental Research
 
Neuroblastoma: in vivo delivery of a miR-380-5p antagonist decreases tumour size in an orthotopic mouse model
 
Read the PubMed abstract
 
To read more about "Neuroblastoma"

 
Nat Med ; 1134-1140 ; October 2010
 
Cushing syndrome: receptor ADRA2A is a potential target for pharmacological treatment
 
Read the PubMed abstract
 
To read more about "Cushing syndrome"

 
J Clin Endocrinol Metab ; E253-E262 ; October 2010
 
Amyotrophic lateral sclerosis: blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function
 
Read the PubMed abstract
 
To read more about "Amyotrophic lateral sclerosis"

 
J Clin Invest ; 3673-3679 ; 1 October 2010
 
Long-QT syndrome: personalised disease models created via patient-specific induced pluripotent stem-cells
 
Read the PubMed abstract
 
To read more about "Familial long QT syndrome"

 
N Engl J Med ; 1397-1409 ; October 2010
 
Clinical Research
 
Metatropic dwarfism and spondylometaphyseal dysplasia, Kozlowski type: TRPV4 mutation spectrum reveals distinct phenotypes
 
Read the PubMed abstract
 
To read more about "Metatropic dwarfism"
To read more about "Spondylometaphyseal dysplasia, Kozlowski type"

 
J Med Genet ; 704-709 ; October 2010
 
Cohen syndrome: high frequency of COH1 intragenic deletions and duplications detected by MLPA in patients
 
Read the PubMed abstract
 
To read more about "Cohen syndrome"

 
Eur J Hum Genet ; 1133-1140 ; October 2010
 
H syndrome and sinus histiocytosis with massive lymphadenopathy: the expanding spectrum of LC29A3 gene disorders
 
Read the PubMed abstract
 
To read more about "H syndrome"
To read more about "Sinus histiocytosis with massive lymphadenopathy"

 
Eur J Med Genet ; 309-313 ; September-October 2010
 
Duchenne muscular dystrophy: dystrophin immunity caused by a partial reversion
 
Read the PubMed abstract
 
To read more about "Duchenne and Becker muscular dystrophy"

 
N Engl J Med ; 1429-1437 ; 7 October 2010
 
Gene Therapy
 
Fanconi anaemia: preclinical correction of complementation group A bone marrow cells via a safety-modified lentiviral vector
 
One of the major hurdles for the development of gene therapy for Fanconi anaemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, the authors developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anaemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC, showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls and increased survival.
Read the PubMed abstract

 
To read more about "Fanconi anemia"

 
Gene Ther ; 1244-1252 ; October 2010
 
Therapeutic Approaches
 
Huntington disease: BDNF regulation under GFAP promoter provides engineered astrocytes as approach for long-term protection
 
Brain-derived neurotrophic factor (BDNF) is the main candidate for neuroprotective therapeutic strategies for Huntington disease. However, the administration system and the control over the dosage are still important problems to be solved. Here the authors generated transgenic mice overexpressing BDNF under the promoter of the glial fibrillary acidic protein (GFAP) (pGFAP-BDNF mice). These mice are viable and have a normal phenotype. However, intrastriatal administration of quinolinate increased the number of reactive astrocytes and enhanced the release of BDNF in pGFAP-BDNF mice compared with wild-type mice. Coincidentally, pGFAP-BDNF mice are more resistant to quinolinate than wild-type mice, suggesting a protective effect of astrocyte-derived BDNF. To verify this, the authors cultured astrocytes from pGFAP-BDNF and wild-type mice for grafting. Wild-type and pGFAP-BDNF-derived astrocytes behave similarly in nonlesioned mice. However, pGFAP-BDNF-derived astrocytes showed higher levels of BDNF and larger neuroprotective effects than the wild-type ones when quinolinate was injected 30 days after grafting. Interestingly, mice grafted with pGFAP-BDNF astrocytes showed important and sustained behavioral improvements over time after quinolinate administration as compared with mice grafted with wild-type astrocytes. These findings show that astrocytes engineered to release BDNF can constitute a therapeutic approach for Huntington disease.
Read the PubMed abstract

 
To read more about "Huntington disease"

 
Gene Ther ; 1294-1308 ; October 2010
 


 
Patient Management and Therapy
 

 
Autoimmune lymphoproliferative syndrome: revised diagnostic criteria and classification
 
Autoimmune lymphoproliferative syndrome (ALPS) is a human genetic disorder of lymphocyte apoptosis resulting in an accumulation of lymphocytes and childhood onset chronic lymphadenopathy, splenomegaly, multilineage cytopenias, and an increased risk of B-cell lymphoma. In 1999, investigators at the National Institutes of Health (NIH) suggested criteria to establish the diagnosis of ALPS. Since then, with approximately 500 patients with ALPS studied worldwide, significant advances in understanding of the disease have prompted the need for revisions to the existing diagnostic criteria and classification scheme. The rationale and recommendations outlined here stem from an international workshop held at NIH on September 21 and 22, 2009, attended by investigators from the United States, Europe, and Australia engaged in clinical and basic science research on ALPS and related disorders. It is hoped that harmonising the diagnosis and classification of ALPS will foster collaborative research and better understanding of the pathogenesis of autoimmune cytopenias and B-cell lymphomas.
Read the PubMed abstract

 
To read more about "Autoimmune lymphoproliferative syndrome"

 
Blood ; e35-e40 ; 7 October 2010
 
Noonan syndrome: clinical features, diagnosis, and management guidelines
 
Noonan syndrome (NS) is a common, clinically and genetically heterogeneous condition characterised by distinctive facial features, short stature, chest deformity, congenital heart disease, and other comorbidities. Gene mutations identified in individuals with the NS phenotype are involved in the Ras/MAPK (mitogen-activated protein kinase) signal transduction pathway and currently explain ∼61% of NS cases. Thus, NS frequently remains a clinical diagnosis. The Noonan Syndrome Support Group (NSSG) is a non-profit organisation committed to providing support, current information, and understanding to those affected by NS. The NSSG convened a conference of health care providers involved in various aspects of NS, to develop these guidelines for use by paediatricians in the diagnosis and management of individuals with NS and to provide updated genetic findings.
Read the PubMed abstract

 
To read more about "Noonan syndrome"

 
Pediatrics ; 746-759 ; October 2010
 
Hodgkin lymphoma: a bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in older patient
 
For older patients with early unfavorable or advanced stage Hodgkin lymphoma (HL) the prognosis is much worse than for younger HL patients. The authors thus developed a new regimen, BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone), to improve both tolerability and efficacy of treatment for older HL patients. Between 2004 and 2005, 65 patients with early unfavorable or advanced stage HL aged between 60 and 75 years were enrolled in this phase 2 trial. Treatment consisted of 6 to 8 cycles of BACOPP. Residual tumour masses were irradiated. Primary endpoints were feasibility as determined by adherence to protocol and overall response rate. The BACOPP regimen is active in older HL patients but is compromised by a high rate of toxic deaths.
Read the PubMed abstract

 
To read more about "Hodgkin lymphoma"

 
Blood ; 2026-2032 ; 23 September 2010
 
Chronic lymphocytic leukaemia: addition of rituximab to fludarabine and cyclophosphamide improves survival
 
The authors investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia. They found that chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia. Moreover, the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytic leukaemia.
Read the PubMed abstract

 
To read more about "Chronic B-cell lymphocytic leukemia"

 
Lancet ; 1164-1174 ; 2 October 2010
 


 
Orphan Drugs
 

 
Does the US Orphan Drug Act need to tighten its net?
 
An article appearing in Health Policy queries whether the USA’s Orphan Drug Act, adopted in 1983, needs to be tweaked to eliminate certain loopholes that allow blockbuster drugs to profit excessively from the incentives the legislation offers to encourage rare disease treatment research and development. The authors cite a number of products that have attained block buster status by extending their indications, thus surpassing the “200,000 or less patients” qualification that defines a rare disease in the USA. Issue is similarly taken with the next category of commercially profitable orphan drugs – those that generate annual global sales between US$ 100-999 million. Attention is also called to the disproportionally large percentage of oncology products that have been developed and approved since the Orphan Drug Act was initiated and the report queries “…whether so many oncology products should qualify for orphan drug designation and whether so many cancers should be considered as rare diseases”. For these and other related issues, the authors call for carefully wrought reforms that do not inadvertently discourage investment and development in the field of rare diseases.
Read the PubMed abstract

 
Big Pharma making rare diseases a priority
 
The past year has ushered in an encouraging trend. Several of the largest biopharmaceutical firms in the world have made a commitment to developing products for rare conditions, often collaborating with smaller biotech firms to develop innovative therapies. In June of this year, OrphaNews Europe reported on the scheme of GlaxoSmithKline (GSK) to develop a new standalone unit directly targeting the development and commercialisation of products for rare disorders. Then in July, the newsletter reported the decision of Pfizer to create a special research unit devoted exclusively to rare diseases that would pursue treatments across all therapeutic areas and modalities. In September, a smaller player, Acceleron Pharma, announced an agreement with Shire to develop and commercialise novel molecules targeting the activin receptor type IIB (ActRIIB) pathway, critical to regulating the growth of skeletal muscle, and central to rare neuromuscular diseases such as Duchenne muscular dystrophy. The most recent step forward comes from GSK, when it unveiled details of its approach to developing rare disease products last month, including a new alliance with the Italian Fondazione San Raffaele and Fondazione Telethon to develop and commercialise an investigational gene therapy for ADA severe combined immune deficiency, which affects only 350 children worldwide. The collaboration will co-develop six additional ex vivo stem cell therapy applications, potentially targeting metachromatic leukodystrophy, Wiskott Aldrich syndrome, beta-thalassaemia, mucopolysaccharoidosis type I, globoid leukodystrophy, and chronic granulomatous disorder. GSK also announced an agreement with Amicus Therapeutics to develop and commercialise Amigal (migalastat HCl), currently in phase three development for the treatment of Fabry disease. Eli Lilly has also entered into collaboration with the Center for Rare and Neglected Diseases at the University of Notre Dame (USA) for the development of a treatment for Niemann-Pick disease type C. Finally, Novartis, via its Institutes for BioMedical Research, is investigating treatments for several 'niche' diseases - including Muckle Wells syndrome, tuberous sclerosis, and cystic fibrosis.
 


 
Grants
 
AFM 2011 Call for Proposals
 
This international call for proposals aims to support research which will lead to a better fundamental understanding of the neuromuscular system; encourage the development of therapies for neuromuscular diseases and rare genetic diseases; and improve care and quality of life of patients with neuromuscular diseases. The second round of proposals for AFM financing closes 4 March 2011 with notification expected in mid July 2011. For further details

 


 
Partnersearch, Job Opportunities
 
Clinical Bioinformatics Training Officer
 
This is an excellent opportunity for an ambitious, motivated and hard-working bioinformatician to lead the training of UK National Health Service clinical scientists in bioinformatics. Responsible for planning and delivering suitable training and developing new opportunities, the candidate will work in a new purpose-built 20-person bioinformatics training suite in the Nowgen Centre. Candidates should have a first degree in computer or biological sciences and a qualification or significant experience in bioinformatics. Knowledge of diagnostic genetic testing would be of particular advantage as would an understanding of the use of bioinformatics in industry and academic research, and the necessary training requirements. For full details and application
 


 
Courses & Educational Initiatives
 

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

 
Orphan Academy 2010-2011 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

 
European Advanced Postgraduate Course in Classical and Molecular Cytogenetics
 
This ten-day course held in February/March each year is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. The students will be trained to identify genetic abnormalities for diagnosis and prognosis, and for fundamental and applied research using both classical and molecular cytogenetic techniques. The course is co-organised by the European Cytogeneticists Association and two French Universities, either as a stand-alone course with only the theoretical part or as a University Diploma including both theoretical and practical training. For further details
 
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?
 

 
Encephalitis Professional Seminar
 
Date: 29 November 2010
Venue: London UK

This seminar presents current studies that contribute to a fuller understanding of the pathogenesis, epidemiology and outcomes of encephalitis.
For further details

 
11th EPPOSI Workshop on Rare Disease Therapy Development Workshop
 
Date: 29-30 November 2010
Venue: Prague, Czech Republic

The topics of this year’s European Platform for Patients’ Organizations, Science and Industry workshop will include: Science - the determinants of rare disease research in Europe: understanding the current and future European Research and Development challenges and opportunities; Regulation - Europe and beyond: developing future regulations and policies for better rare disease therapies; and Sustainable Access - the reality we face to improve access to and affordability of orphan drugs.
For further details

 
World Orphan Drug Congress
 
Date: 29 November – 1 December 2010
Venue: Geneva, Switzerland

Showcasing leading commercial strategies and orphan drug successes, and offering insight into the successful development, authorisation and reimbursement of rare disease drugs.
For further details

 
Syringomyelia 2010: International Symposium
 
Date: 9-11 December 2010
Venue: Berlin, Germany

Topics will include: pathophysiology of syringomyelia; diagnostics; clinical entities: chiari malformation, dysraphism, tethered cord, posttraumatic syringomyelia, syringomyelia due to spinal arachnopathies; and therapy: surgical, conservative, outcome; rehabilitation.
For further details

 
4th International Meeting on the Congenital Disorders of Glycosylation and Related Disorders
 
Date: 13-14 January 2011
Venue: Leuven, Belgium

The 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. The meeting is organised by EUROGLYCANET, a European network for the advancement of research, diagnosis and treatment of a growing group of rare disorders.
For further details

 
2nd Annual Commercialisation & Market Access Strategies for Orphan & Ultra-Orphan Drugs
 
Date: 17 February 2011
Venue: Barcelona, Spain

The event will be focused on orphan therapies and will guarantee all participants access to today’s most relevant case studies and views which directly affect their future business plans and can assist them to maximise market and patient access.
For further details

 
Third International Symposium on Paediatric Movement Disorders
 
Date: 25-26 February 2011
Venue: Barcelona, Spain

This event aims to continue the collaborative activities between professionals interested in paediatric movement disorders, mainly neurologists and neuropaediatricians. As in the previous symposiums qualified experts in the different aspects involved in paediatric movement disorders will increase knowledge, and serve to establish interesting contacts and develop creative ideas. Some newly recognised and treatable inborn errors of metabolism that may present with movement disorders in childhood (i.e. Glut-1 Deficiency, Cerebral Folate Deficiency and Dopamine Transporter Defects) will be presented. Deadline for abstract submission: 15 December 2010 For further details

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

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

 
Second ASID Congress of the African Society for Immunodeficiencies
 
Date: 10-13 March 2011
Venue: Hammamet, Tunisia

This second congress 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

 
11th International Congress of the European Society of Magnetic Resonance in Neuropediatrics
 
Date: 24-26 March 2011
Venue: Amsterdam, Netherlands

Bringing together neuroscientists, paediatric neurologists, scientists interested in developmental paediatrics, neonatologists, neuroradiologists, neuropsychologists, neurophysiologists and physicists to discuss the newest developments in advanced neuroimaging and image guided therapeutic approaches in the fields of normal and abnormal brain development and brain functions, which will be presented by internationally recognised experts.
For further details

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

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

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

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

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

A global meeting on international cooperation and public health policies focussing on research, diagnosis, development of and access to treatment and care for rare diseases. The programme for this conference will be available shortly.
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. Deadline for abstract submission: 28 February 2011.
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

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

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

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

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

 


 
Press & Publications
 
New textbook on rare disease epidemiology covers many areas of the field
 

Rare Diseases Epidemiology
is a new text that analyses the epidemiological research constraints in the field of rare diseases, presenting the experiences of experts on many aspects – including the development of patient registries; the collection, storage and selected distribution of bio-specimens from bio-banking activities; the validation and utilization of genetic testing and newborn screening procedures; the presentation of issues related to the importance of case reports to increase knowledge of rare diseases; the challenges and models for population-based surveillance studies for rare congenital and inherited disorders; the statistical methods for the geographical analyses of rare diseases; the value and need for clinical trials and comparative effective studies; and meeting the requirements of regulatory agencies. Various economic, societal, and ethical concerns are presented. The rare diseases research framework programmes as developed by the European Union are evoked along with the value of national plans for individual member countries. Similar programmes that have been implemented in the USA as a result of the Orphan Drug Act to address the needs of the rare diseases community are also elicited.

Authors: Posada de la Paz, M; Groft, SC -Eds.
Publisher: Springer, September 2010
ISBN-13: 978-9048194841

 


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