21 May 2008 print
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Editorial
 
France takes stock of its rare disease plan and pledges to promote European cooperation during upcoming EU presidency
 
France’s Minister of Health, Roselyne Bachelot-Narquin, last week presented a discourse on the occasion of the third reunion of the committee responsible for evaluating the country’s rare disease plan which was launched in 2005 for a four-year period. France was the first European country to implement a rare disease plan, which has been widely used as a model by other countries. Minister Bachelot-Narquin evoked various elements of the plan that have been successfully undertaken, including the designation of 132 centres of reference to date encompassing 17 different categories of rare diseases that allow for the development of specialised expertise for these diseases; improved diagnostics, particularly in the domain of molecular biology; the elaboration of quality information disseminated freely to patients and professionals – notably via Orphanet, the European portal for rare diseases; and research – under the French rare disease plan over 70 projects have been financed at the cost of 26 million euros. The ten principal elements of the plan are now being reviewed in order to determine those that have met their objectives and those that need continued support. The Health Minister, underscoring her support for the provisions of the European Commission's Communication on European Action in the Field of Rare Diseases, emphasised the need for European-level collaboration in the field of rare disease and orphan drugs and reiterated the priority France would give to this issue when it assumes the EU presidency in July. Read the speech of the Health Minister (in French).
 


 
EU Policy News
 
Innovative Medicines Initiative kicks off with first call for proposals
 
As was reported in the 30 January issue of OrphaNews Europe, the European Council adopted four Joint Technology Initiatives (JTIs) in December 2007 – including the Innovative Medicine Initiative Joint Undertaking (IMI JU). JTIs are public-private partnerships between the Commission and industry (and in some cases the Member States), implemented by Joint Undertakings on the basis of Article 171 of the EU Treaty. Founded by the European Commission and the EFPIA (European Federation of Pharmaceutical Industries and Associations), the IMI JU will support pre-competitive pharmaceutical research and development. Its goal is to deliver new approaches, methods and technologies for the drug development process in order to accelerate the development of safe and more effective medicines for patients – including medicinal products for rare diseases. The IMI Governing Board held their official kick-off meeting in early March during which members prepared for the first Call for Proposals. The Call launched on 30 April as part of the IMI Annual Implementation Plan 2008, following recommendations of the Strategic Research Agenda to reduce principal research bottlenecks in the biopharmaceutical research and development process by focusing on four areas: predicting safety; predicting efficacy; knowledge management; and education and training. Amongst the topics in this first call: improving immunogenicity predictivity; non-genotoxic carcinogenesis; and improved predictivity of non-clinical safety evaluation. The opening date for submitting an expression of interest is 1 June 2008. The closing date is 15 July 2008.
 
DG Research
 
E-Rare holds two rare disease workshops
 
E-Rare (an ERA-Net activity for research programmes on rare diseases) is a consortium of 10 partners, including public bodies, ministries and research management organisations from eight countries, responsible for the development and management of national/regional research programmes on rare diseases. Since June 2006, E-Rare has been implementing a cooperation project funded by the European Commission through the Sixth Framework Programme that aims at overcoming the fragmentation and duplication of research on rare diseases in the participating countries. Through the development of joint and strategic activities, E-Rare strives to promote cooperation among European research teams producing new knowledge in the field of rare diseases, thus providing maximized efficiency and impact to rare disease research.



Within the framework of its strategic activities, E-Rare recently organised two back-to-back workshops that targeted two important themes: Clinical Trials on Rare Diseases and The Natural History of Rare Diseases. The first topic included presentations from experts in the field of clinical trials for rare diseases who highlighted subjects such as clinical trial mapping in Europe, applying clinical trial methodology to rare diseases, an industry perspective on testing drugs for rare diseases, ethical and legal problems, new treatments, multicentre and multinational trials, patient perspectives, trial registration for rare diseases, and EMEA expectations in orphan drug research. The second theme, exploring natural history and rare diseases, encompassed concepts and methods for studying the natural history of a disease, translational research, ethical considerations, funding sustainability, and advisory board recommendations. The workshops, held at Instituto de Salud Carlos III in Madrid on 14-15 April, thus provided insight into two important topics that could contribute to policy making and help to inform the preparation of E-Rare’s second joint transnational call for proposals. As was reported in the 19 March, 2008 issue of OrphaNews Europe, the first E-Rare joint transnational call was launched in 2007. Thirteen projects (involving 76 research teams) were selected from over 120 proposals and received funding for a global amount of over 9 million euros. The funded projects include research targeting (among other topics) craniofacial malformations, autoimmune liver diseases, Rett syndrome, spastic paraplegias, Hirschsprung disease, Kindler syndrome, and spinocerebellar ataxia. The conclusions of the workshops are scheduled to be posted shortly on the E-Rare website. A new call for proposals is expected to be launched by the end of the year.
 


 
National & International Policy Developments
 
Motion M-426: A call for a rare disease plan in Canada passes in House of Commons
 
The First European Rare Diseases Day was celebrated as far away as Canada, where it was also the occasion for a member of parliament (MP) from Vancouver to unveil a motion calling for a national rare disease policy. Don Bell, a MP from North Vancouver, lost a grandson to a rare disorder last July, according to CORD, the Canadian Organisation for Rare Diseases. Mr. Bell has created private member Motion M-426, presented at a House of Commons Debate in mid April. The motion, following an initiative promoted by CORD, seeks to:

establish a definition for serious rare disorders as those with a prevalence of less than 1 in 2000 Canadians; examine the feasibility of a national “Chance for Life Fund” equivalent to 2% of the total annual public drug expenditure to be designated for therapies for rare disorders; consider the establishment of a multi-stakeholder advisory body, including treaters and patients, to recommend treatment access for life-threatening or serious rare disorders, based on scientific standards and social values; consider the establishment of centres of reference for specific rare disorders, comprised of national and international experts, who will develop criteria for treating patients based on scientific evidence and patient impact and provide on-going surveillance into the real-world safety and effectiveness of these treatments on individual and group basis; consider options to provide incentives through orphan drug regulation and policy, to assure Canadian organisations and researchers are motivated to conduct research and development into treatments for rare and neglected disorders; support internationally accepted standards for conduct of clinical trials in rare disorders appropriate for the challenges inherent to very small patient populations; consider ensuring that Health Canada’s progressive licensing framework provide appropriate support to the design of clinical trials for very small patient populations and appropriate review of evidence submitted from these trials; and report the progress accomplished to the House within six months.

The motion has been worded deliberately to ensure it could be immediately “votable” and not require “government expenditure or other procedural restrictions to its passage”. Canada is amongst a dwindling handful of developed countries that do not yet have rare disease and orphan medicine policies in place to encourage the development of rare disease research and treatments. Whether or not a medicinal product is funded varies from region to region under the current health scheme. The Canadian press recently reported widely the case of a young Hunter syndrome patient who could not access an expensive but effective treatment that was not funded in his home province of Ontario, though it is funded in other regions of the country, such as British Columbia. The House of Commons approved Motion M-426 on 7 May. It is now up to the government to examine and respond specifically to the challenges delineated in the motion. Read the Motion hearing

 
Other European news
 
Irish firm develops newborn screening kits targeting under-developed countries
 
Enzolve Technologies, a spin-off from the University College Dublin based at the university’s NOVA UCD Innovation and Technology Transfer Centre, has developed a range of cost-effective diagnostic kits for screening newborn infants. The NeoScreenPak features a single format test package that uses the same standard platform for all tests, thus eliminating different set ups for different tests. The first NeoScreenPak will contain an initial test that screens for phenylketonuria (PKU). Each kit will contain materials permitting up to 1000 newborns to be tested. Other diseases targeted include maple syrup urine disease, homocystinuria, galactosaemia, tyrosinemia type I, dehydrogenase deficiency and biotinidase deficiency. These disorders cause long-term damage if undetected and untreated. The company reports that China, Russia and Brazil have all shown interest. There are currently wide discrepancies between newborn screening policies around the world, with under-developed countries less able to furnish screening for their newborns.
 


 
Orphanet News
 
OJRD definitely on the right track…
 
Barely two years since its debut, the Orphanet Journal of Rare Diseases (OJRD) is extremely pleased to announce that it has been chosen for impact factor tracking by the reputable Thomson Scientific (ISI).

Thomson, the recognised authority for evaluating journals, and the inventor of the impact factor, is selective in choosing publications to track, seeking out publications that produce high quality research and writing, and show stability and maturity. The impact factor produces a measure of the frequency a given article is cited within a specific timeframe. OJRD intends to keep working hard to prove itself worthy of this latest honour and thanks all its editors, authors and reviewers for their contributions toward excellence on behalf of rare disease patients and their families across the world. Tracking is due to begin in June. Learn more about the Thomson Scientific Impact Factor

 
New Texts
 
New Orphanet Journal of Rare Diseases publications
 
McCune-Albright syndrome
 
New Research Projects open for Recruitment
 
A clinical trial recruiting in France
 
A multinational, multicentre, randomized, double-bind study to assess the efficacy and safety of sildenafil added to Bosentan in the treatment of subjects aged 18 years and above with pulmonary arterial hypertension
 


 
New Genes
 
Autosomal-recessive spastic paraplegia: identification of the ZFYVE26 gene as a frequent cause
 
Hereditary spastic paraplegias (HSPs) are genetically and phenotypically heterogeneous disorders. Both "uncomplicated" and "complicated" forms have been described with various modes of inheritance. Sixteen loci for autosomal-recessive "complicated" HSP have been mapped. The SPG15 locus was first reported to account for a rare form of spastic paraplegia variably associated with mental impairment, pigmented maculopathy, dysarthria, cerebellar signs, and distal amyotrophy, sometimes designated as Kjellin syndrome. Here, the authors report the refinement of SPG15 to a 2.64 Mb genetic interval on chromosome 14q23.3-q24.2 and the identification in eight families of ZFYVE26, which encodes a zinc-finger protein with a FYVE domain that they named spastizin.
Read the PubMed abstract

 
American Journal of Human Genetics ; 992-1002 ; April 2008
 
Autosomal dominant thrombocytopenia: beta3 integrin activation explains platelet anomaly
 
The authors report five individuals affected with a dominantly inherited macrothrombocytopenia. All five carry mutations in the gene encoding beta3 integrin . The authors conclude that the constitutive activation of the alpha IIb beta3-H723 receptor causes abnormal proplatelet formation, leading to incorrect sizing of platelets and the thrombocytopenia observed in the pedigree.
Read the PubMed abstract

 
Blood ; 3407-3414 ; April 2008
 
Autosomal dominant thrombocytopenia: first identification of a mutation affecting cytochrome C
 
The authors report the first identified mutation in the gene encoding human cytochrome c (CYCS) in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. Glycine 41, invariant throughout eukaryotes, is substituted by serine. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. The family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis.
Read the PubMed abstract

 
Nature Genetics ; 387-389 ; April 2008
 
Bardet-Biedl syndrome: mutations in genes associated with Meckel-Gruber syndrome
 
Meckel-Gruber syndrome (MKS) is a genetically heterogeneous, neonatally lethal malformation and the most common form of syndromic neural tube defect (NTD). To date, several MKS-associated genes have been identified whose protein products affect ciliary function. Here the authors show that mutations in MKS1, MKS3 and CEP290 (also known as NPHP6) either can cause Bardet-Biedl syndrome (BBS), characterised by obesity, pigmentary retinopathy, postaxial polydactyly, hypogenitalism (especially in male subjects), renal disorders, and learning difficulties or, in some cases, moderate intellectual deficit. These mutations may have a potential epistatic effect on mutations in known BBS-associated loci. Five of six families with both MKS1 and BBS mutations manifested seizures, a feature that is not a typical component of either syndrome.
Read the PubMed abstract

 
Nature Genetics ; 443-448 ; April 2008
 
Amyotrophic lateral sclerosis: TDP-43 mutations in familial and sporadic forms
 
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterised by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. The authors of this study identified neighbouring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBP mutation M337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. This evidence suggests a pathophysiological link between TDP-43 and ALS.
Read the PubMed abstract

 
Science ; 1668-1672 ; March 2008
 
Diffuse large B cell lymphoma: CARD11 mutations linked to tumour cell survival
 
Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. In normal B cells, antigen receptor-induced NF-kappaB activation requires CARD11, a cytoplasmic scaffolding protein. To determine whether CARD11 contributes to tumorigenesis, the authors sequenced the CARD11 gene in human DLBCL tumors. They detected missense mutations in 7 of 73 DLBCL biopsies (9.6%), demonstrating that CARD11 is a oncogene in DLBCL, and providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.
Read the PubMed abstract

 
Science ; 1676-1679 ; March 2008
 
Congenital fiber type disproportion: Mutations in TPM3 are a common cause
 
Congenital fiber type disproportion (CFTD) is a rare form of congenital myopathy in which the principal histological abnormality is hypotrophy of type 1 (slow-twitch) fibers compared with type 2 (fast-twitch) fibers. To date, mutation of ACTA1 and SEPN1 has been associated with CFTD, but the genetic basis in most patients is unclear. The gene encoding alpha-tropomyosin(slow) (TPM3) is a rare cause of nemaline myopathy, previously reported in only five families. The authors investigated whether mutation of TPM3 is a cause of CFTD by sequencing TPM3 in 23 unrelated probands with CFTD or CFTD-like presentations of unknown cause. They identified novel heterozygous missense mutations in five CFTD families. Mutation of TPM3 is the most common cause of CFTD reported to date.
Read the PubMed abstract

 
Ann Neurol ; 329-337 ; March 2008
 
Mitochondrial complex I deficiency can be caused by a deleterious NDUFA11 mutation
 
Complex I deficiency is the most common respiratory chain defect, clinically manifesting by severe neonatal lactic acidosis, Leigh disease, or various combinations of cardiac, hepatic, and renal disorders. Using homozygosity mapping, the authors identified a splice-site mutation in the NDUFA11 gene in six patients from three unrelated families. The patients presented with encephalocardiomyopathy or fatal infantile lactic acidemia. The mutation is predicted to abolish the first transmembrane domain of the gene product, thereby destabilizing the enzymatic complex. Mutation analysis of the NDUFA11 is thus warranted in isolated complex I deficiency presenting with infantile lactic acidemia or encephalocardiomyopathy.
Read the PubMed abstract

 
Ann Neurol ; 405-408 ; March 2008
 
Hypotrichosis simplex: A G protein-coupled receptor is involved in hair growth
 
Hypotrichosis simplex is a group of nonsyndromic human alopecias. The authors mapped an autosomal recessive form of this disorder to chromosome 13q14.11-13q21.33, and identified homozygous truncating mutations in P2RY5, which encodes an orphan G protein-coupled receptor. This study is the first to implicate a G protein-coupled receptor as essential for and specific to the maintenance of human hair growth and may provide opportunities for new therapeutic approaches to the treatment of hair loss in humans.
Read the PubMed abstract

 
Nature Genetics ; 329-334 ; March 2008
 


 
Research in Action
 
Clinical Research
 
Type 1 von Willebrand disease: a correlation between genotype and desmopressin response
 
The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. In this study, the authors report the assay of VWF propeptide (pp) and VWF in 19 individuals recruited from six European centres. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the 7 individuals. Thus, a substantially increased ratio of steady-state VWFpp/VWF:Ag predicted a reduced VWF half-life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a subpopulation of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.
Read the PubMed abstract

 
Blood ; 4979-4985 ; March 2008
 
Limb girdle muscular dystrophy type 2B: certain patients have amyloidosis
 
Dysferlin (DYSF) gene mutations cause limb girdle muscular dystrophy type 2B and Miyoshi's myopathy. The consequences of DYSF mutations on protein structure are poorly understood. In this study, the gene encoding dysferlin was sequenced in patients with suspected dysferlin-deficient muscular dystrophy. Muscle biopsy specimens were analyzed by histochemistry, immunohistochemistry, and electron microscopy. The authors found three families with muscular dystrophy caused by homozygous or compound heterozygous DYSF mutations featuring sarcolemmal and interstitial amyloid deposits. Dysferlin was a constituent of the amyloid deposits. Molecular treatment strategies will necessarily have to consider the presence of amyloidogenesis.
Read the PubMed abstract

 
Ann Neurol ; 323-328 ; March 2008
 
X-linked mental retardation: 215 disease variations and 82 genes identified
 
X-linked mental retardation (XLMR) is a common cause of inherited intellectual disability with an estimated prevalence of approximately 1/1000 males. Most XLMR conditions are inherited as X-linked recessive traits, although female carriers may manifest usually milder symptoms. The authors here have listed 215 XLMR conditions, subdivided according to their clinical presentation: 149 with specific clinical findings, including 98 syndromes and 51 neuromuscular conditions, and 66 nonspecific forms. They also present a map of the 82 XLMR genes cloned to date (November 2007) and a map of the 97 conditions that have been positioned by linkage analysis or cytogenetic breakpoints.
Read the PubMed abstract

 
European Journal of Human Genetics ; 422-434 ; April 2008
 
Therapeutic Approaches
 
Muscular dystrophy: Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates the condition
 
Muscular dystrophies comprise a diverse group of genetic disorders that lead to muscle wasting and, in many instances, premature death. Many mutations that cause muscular dystrophy compromise the support network that connects myofilament proteins within the cell to the basal lamina outside the cell, rendering the sarcolemma more permeable or leaky. Here the authors show that deletion of the gene encoding cyclophilin D rendered mitochondria largely insensitive to the calcium overload-induced swelling associated with a defective sarcolemma, thus reducing myofiber necrosis in two distinct models of muscular dystrophy. Moreover, the premature lethality associated with deletion of Lama2, encoding the alpha-2 chain of laminin-2, was rescued, as were other indices of dystrophic disease. Mitochondrial-dependent necrosis represents a prominent disease mechanism in muscular dystrophy, suggesting that inhibition of cyclophilin D could provide a new pharmacologic treatment strategy for these diseases.
Read the PubMed abstract

 
Nature Medicine ; 442-447 ; April 2008
 
Diagnostic Approaches
 
Hemochromatosis: measuring ferritin levels is more effective screening technique than measuring transferrin
 
Hemochromatosis is a genetic disease characterised by a surcharge of iron due to digestive hyperabsorption. Because the penetrance of hemochromatosis is low, traditional population screening measuring the transferrin saturation is unlikely to be cost-effective because the majority of subjects detected neither have clinical disease nor are likely to develop it. Three independent studies show that only patients with serum ferritin concentrations more than 1000 microg/L are at risk for cirrhosis, one of the main morbidities of hemochromatosis. Among 29,699 white subjects participating in the Scripps/Kaiser hemochromatosis study, only 59 had serum ferritin levels more than 1000 microg/L; 24 had homozygous mutant or compound heterozygous mutant HFE genotypes. Screening for hemochromatosis with serum ferritin levels will detect the majority of patients who will be clinically affected and may detect other clinically significant disease in patients who do not have hemochromatosis genotypes.
Read the PubMed abstract

 
Blood ; 3373-3376 ; April 2008
 
Global developmental delay or intellectual disability in children: comparative genomic hybridisation doubles diagnoses
 
This review examines the recent discovery of large-scale copy number variations in the human genome and advances in microarray technology which together have changed the clinical genetic diagnostic approach for children with global developmental delay. Molecular testing for chromosome imbalances has changed with the application of array comparative genomic hybridisation. Recent publications suggest a doubling of the rate of diagnosis of patients with genome copy number abnormalities as the cause of developmental delay. The use of array comparative genomic hybridisation is replacing the use of fluorescent in-situ hybridisation techniques for the child with idiopathic global developmental delay or intellectual disability.
Read the PubMed abstract

 
Curr Opin Neurol ; 117-122 ; April 2008
 
Autism spectrum disorders: Genetics evaluation for etiologic diagnosis
 
Over the past decade, the reported incidence of autism spectrum disorders has continued to increase. Coincident with this, the number of referrals to clinical geneticists to identify the etiology has also dramatically increased. The list of genetic and metabolic conditions that have been reported with an autism phenotype is quite extensive. In deciding on an evaluation plan, the clinical geneticist has the difficult task of balancing an ever-expanding list of available tests and possible diagnoses with the issues of cost, practicality, and expected yield. In this article, the authors discuss a strategy of a tiered evaluation of the etiology of autism. These recommendations use evidence-based conclusions from the current available literature and cumulative clinical experience.
Read the PubMed abstract

 
Genet Med ; 4-12 ; January 2008
 


 
Patient Management and Therapy
 
Hypereosinophilic syndrome: mepolizumab reduces corticosteroid use
 
The hypereosinophilic syndrome is a group of diseases characterised by persistent blood eosinophilia, defined as more than 1500 cells per microlitre with end-organ involvement and no recognised secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity. The authors conducted an international, randomised, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti-interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks. The primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group. A blood eosinophil count of less than 600 per microlitre for 8 or more consecutive weeks was achieved in 95% of patients receiving mepolizumab. This study shows that treatment with mepolizumab, an agent designed to target eosinophils, can result in corticosteroid-sparing for patients who have the hypereosinophilic syndrome.
Read the PubMed abstract

 
NEJM ; 1215-1228 ; March 2008
 
Prader-Willi syndrome: growth hormone treatment also effective in adults
 
Growth hormone replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies. The authors of this study evaluated the effectiveness and safety of growth hormones in 30 genotype-positive PWS adults via a 12-month open-label multicentre trial with 6-month dose-optimisation and 6-month stable treatment periods. The study demonstrated that growth hormone improves body composition, normalises T(3), and is well tolerated without glucose impairment in PWS genotype adults.
Read the PubMed abstract

 
J Clin Endocrinol Metab ; 1238-1245 ; April 2008
 
Systemic-onset juvenile idiopathic arthritis: efficacy and safety of tocilizumab demonstrated
 
Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including anti tumour-necrosis-factor agents. The authors investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in 56 children with this disorder. Tocilizumab proved effective in children with systemic-onset juvenile idiopathic arthritis. The authors propose that it might therefore be a suitable treatment in the control of this disorder.
Read the PubMed abstract

 
The Lancet ; 998-1006 ; March 2008
 
Systemic mastocytosis: encouraging results with thalidomide in two patients
 
Systemic mastocytosis is an acquired orphan disease characterised by the abnormal accumulation of mast cells responsible for organ failure and systemic symptoms. Cytoreductive drugs have been shown to be effective, but have rarely resulted in complete or long-term remission. The authors report two patients with advanced systemic mastocytosis who were treated successfully with thalidomide, given at the maximal tolerated dosage. After a follow-up of more than 1 year, the patients remained in partial remission. Clinical trials are warranted to define efficacy and safety profiles for this molecule.
Read the PubMed abstract

 
Br J Haematol ; 249-253 ; April 2008
 
Familial hypercholesterolemia: ezetimibe does not reduce atherosclerosis risk
 
Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown. The authors conducted a double-blind, randomised, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia. Combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima-media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein.
Read the PubMed abstract

 
NEJM ; 1431-1443 ; April 2008
 
What is ideal genetic counselling? A survey of current international guidelines
 
The objective of this article is to review guidelines that address counselling in the context of genetic testing in order to summarise what aspects of counselling are considered most important, and to examine how they construct the ideal of genetic counselling. Guidelines were collected by examining the websites of different international professional, political, ethical and patient organisations. The most frequently mentioned topics in the collected 56 guidelines were examined. The ideal of genetic counselling is expressed in the analysed guidelines as being composed of (1) an appropriately trained professional who understands genetics and its ethical implications well; (2) relevant and objective information; (3) assurance of the counsellee's understanding; (4) psychological support; (5) informed consent; (6) confidentiality of genetic information; (7) considering familial implications; (8) appropriate handling of potential discrimination of testing; and (9) assuring autonomous decision-making by the counsellee. The ideal of genetic counselling is rather consistent in the guidelines, but there are some contradictions between the requirements of objective information-giving and adapting counselling to counsellee's circumstances.
Read the PubMed abstract

 
European Journal of Human Genetics ; 445-452 ; April 2008
 


 
Courses & Educational Initiatives
 
A unique online MSc course in haemoglobinopathies
 
Thalassaemia International Federation (TIF) in collaboration with University College London (UCL) is offering a unique online MSc course in Haemoglobinopathies. The first e-learning course in this field, the course offers health professionals the opportunity to pursue an advanced degree from anywhere in the world. For further information
 
European Advanced Postgraduate Course in Classical and Molecular Cytogenetics - 2009
 
The course is designed to provide medical graduates, pharmacists, researchers, graduate students and health professionals with advanced training in constitutional, haematological, and oncological cytogenetics. The students will be trained to identify genetic abnormalities using both classical and molecular cytogenetic techniques for diagnosis, prognosis, and fundamental and applied research. The course is co-organised by the European Cytogenetists 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 information
 


 
What's on Where?
 
13th International Conference for Behçet's Disease and 5th Patients' Convention
 
Date: 24-27 May 2008
Venue: Klagenfurt, Austria

With presentations and discussions on oral, eye, genital and skin involvement, as well as paediatric patients, drug trials and future perspectives.
For further details

 
Myology 2008: Treatments – The Turning Point
 
Date: 29 May - 1 June 2008
Venue: Marseilles, France

Focusing on the development of therapies and the setting up of trials on humans for rare diseases in the field of myology.
For further details

 
First Conference on Translational Research in Paediatric Rheumatology
 
Date: 29 May - 1 June 2008
Venue: Genoa, Italy

Using the field of rare paediatric rheumatic disorders as a paradigm, Anticipating Changes in Drug Development for Children: Building on Paediatric Rheumatology will examine the medicine research and development process, from pre-clinical and early-phase clinical development, to biomarker validation, study design and management, data analysis, ethical review, regulatory submission and research governance. The conference is meant to further stimulate interaction among the three major stakeholders in the drug development process, namely, academia, industry and regulatory authorities.
For further details

 
5th International Congress of Rehabilitation in the Field of Neuromuscular Disorders
 
Date: 30 May – 1 June 2008
Venue: Marseilles, France

With sessions on gene-based therapies, patient evaluation, pain and fatigue management, and treatment options.
For further details

 
EuroGentest Genetic Testing Accreditation and Quality Assurance Programmes
 
Date: 30-31 May 2008
Venue: Barcelona, Spain

EuroGentest presents two workshops and a round table session on the topics of accreditation in genetic testing labs, quality assurance and managing the human side of change.
For further details

 
International Down Syndrome Screening Group 8th International Congress
 
Date: 31 May- 1 June 2008
Venue: Vancouver, Canada

Held in conjunction with the International Society for Prenatal Diagnosis conference, taking place immediately afterward.
For further details

 
40th European Human Genetics Conference
 
Date: 31 May-3 June 2008
Venue: Barcelona, Spain

In conjunction with the European Meeting on Psychosocial Aspects of Genetics 2008. Progamme will cover the latest developments in the field of human genetics that are of interest both for clinicians and research scientists.
For further details

 
14th International Conference on Prenatal Diagnosis and Therapy
 
Date: 1-4 June 2008
Venue: Vancouver, Canada

Conference sessions will include foetal imaging, cytogenetics, foetal DNA/RNA, PGD, screening, teratology, and legal aspects of prenatal diagnostics and therapy.
For further details

 
5th International Conference on Alpha1-antitrypsin Deficiency
 
Date: 10 June 2008
Venue: Birmingham, UK

Conference sessions will include genetic and environmental factors, screening, and treatment approaches.
For further details

 
5th International Cystinosis Conference
 
Date: 27-28 June 2008
Venue: Dublin, Ireland

World experts in the field of Cystinosis will attend and the latest research in this very rare disease will be presented. The event is unique as it combines a high-level scientific and medical conference as well as being a family and patient friendly conference.
For further details

 
15th International Paediatric Colorectal Club Meeting
 
Date: 29 June- 1 July 2008
Venue: Salamanca, Spain

For further details

 
Fourth International Neuroacanthocytosis Symposium: Bridging Clinical and Basic Aspects
 
Date: 1-2 July 2008
Venue: Oxford and London, England

Including clinical aspects of chorea acanthocytosis and McLeod syndrome, muscle and nerve neuropathology and syndromes related to NA. View the programme.
For further details

 
15th Retina International World Congress
 
Date: 4-5 July 2008
Venue: Helsinki, Finland

Clinical diagnostics of retinal dystrophies, genetic diagnostics and research, Usher syndrome, ongoing clinical trials.
For further details

 
Supporting Policy Development in Genomics Symposium
 
Date: 6 July 2008
Venue: Montreal, Canada

Policy-makers and researchers from a variety of fields are convened to this international symposium in view of outlining a roadmap towards a more concerted research approach to inform policy.
For further details

 
New and Developing Technologies for Genetics Diagnostics
 
Date: 7-8 July 2008
Venue: Salisbury, UK

This meeting will cover a wide range of techniques and issues relevant to genetic diagnostics in the 21st century. The meeting will focus on new sequencing technologies, non-invasive prenatal diagnosis, molecular cytogenetics copy number determination.
For further details

 
Fourth International Conference on Metals and Genetics
 
Date: 21-24 July 2008
Venue: Paris, France

The main topics will include metal-associated diseases: molecular and systemic biology approaches; characterisation and speciation of metal in proteins and biological tissues; and metals and environmental health implications.
For further details

 
Barth Syndrome: On Track Toward a Cure - 4th International Conference
 
Date: 21-26 July 2008
Venue: Florida, USA

This conference will be dedicated to increasing knowledge and accelerating advances in research for this rare metabolic genetic disorder. It will bring together basic scientists, clinical researchers, treating physicians, other professionals, and affected individuals and families to focus on the syndrome through a series of carefully organised sessions.
For further details

 
Inaugural Birt Hogg Dube Syndrome Symposium
 
Date: 3 September 2008
Venue: Roskilde, Denmark

Laboratory research session in the morning and a clinical session in the afternoon. Keynote presentation and opportunity for a number of short talks in each session. There will be poster presentations. This is an opportunity for researchers and clinicians to present their work, share ideas and set up collaborations to promote BHD research and to establish screening guidelines for BHD patients. Deadline for abstract submission is 15 June, 2008.
For further details

 
6th International Conference on Frontotemporal Dementia
 
Date: 3-5 September 2008
Venue: Rotterdam, The Netherlands

Symposium highlights include: Caregivers burden; Early onset dementia AD; Genetic Counseling; Aphasic syndromes; Tau; Progranulin; TDP-43 protein; Genetics of the FTD; ALS spectrum; Animal and Cell Models; Neuropathology and biochemistry of FTD; Clinical spectrum FTD; Pharmacological treatments; and more.
For further details

 
15th Paediatric Rheumatology European Society Congress
 
Date: 14-17 September 2008
Venue: University College London, UK

The programme will cover four main topics through keynote lectures, abstract presentations and educational workshops: juvenile arthritis, juvenile dermatomyositis, vasculitis and pain. There will be novel symposia such as sport and exercise in young people.
For further details

 
2nd Congress of Ring14 International Association for Rare Neurogenetic Diseases Research
 
Date: 25-27 September 2008
Venue: Reggio Emilia, Italy

An interesting and varied programme for professionals, patients and their families.
For further details

 
13th International Meeting of the World Muscle Society
 
Date: 29 September - 2 October 2008
Venue: Newcastle upon Tyne, UK

New Insights into the pathogenesis of facioscapulohumeral muscular dystrophy, myotonic dystrophy and other dominant muscular dystrophies, Advances in the understanding and treatment of myasthenic disorders, Therapeutic advances in neuromuscular disorders, Advances across the neuromuscular field, including treatment and management.
For further details

 
6th World Rett Syndrome Congress
 
Date: 10-13 October 2008
Venue: Paris, France

Various aspects of Rett syndrome and MECP2 functioning, including fundamental, clinical and management topics.
For further details

 
Tenth International Meeting on Osteogenesis Imperfecta
 
Date: 15-18 October 2008
Venue: Ghent, Belgium

Topics include: Bone homeostasis, murine models/collagen biology/biophysics, classification, genetics: genotype-phenotype, prenatal diagnosis/preimplantation diagnosis, biphosphonates, orthopedic management, hearing loss: physiopathology, surgery and imaging, other medical management issues, stomatology/dentistry, psychosocial aspects, new (therapeutic) perspectives.
For further details

 
EPPOSI 9th Workshop on Partnering for Rare Diseases Therapy Development
 
Date: 16-17 October 2008
Venue: Paris, France

Mark your calendars for the 2008 EPPOSI workshop, taking place at the National Assembly in Paris. The theme of the workshop is Orphan drugs: partnering along the chain and across the borders - Sharing strategies and tools for access to diagnosis and treatment.
For further details

 
Rare Tumors in Europe: Challenges and Solutions
 
Date: 6 November 2008
Venue: Brussels, Belgium

Details to follow shortly.
For further information

 


 
Press & Publications
 
Orphan drug legislation provides a model for neglected tropical disease drug development
 
An article published recently in the International Journal of Health Planning and Management explores how orphan drug policies could be used as a model for neglected tropical diseases. Orphan drug legislation: lessons for neglected tropical diseases is written by researchers from Italy and the US, who propose that the type of orphan drug legislation in place in the US, Europe, Japan and Australia could be adapted to stimulate the development of medicinal products for neglected tropical diseases. Current orphan drug legislation offers incentives - including an exclusivity period, tax credits, fee exemptions, research grants, protocol assistance, and fast-track procedures - for companies to invest in the research and development of medicinal products that by their definition will have a small commercial market. While neglected tropical diseases can have high prevalence, they typically afflict patients in parts of the world where per capita income is very low and governments are too strapped to provide funding for medications for their citizens. The authors point out that the success of the orphan drug legislation lends evidence to the fact that orphan drug programmes can still generate profits – even with small markets. Would the same be true for medications targeting larger populations but made available at lower prices? Although current opinion tends to believe that neglected tropical disease medication development should be the responsibility of major multinationals, the orphan drug legislation demonstrates that smaller innovative companies, universities and non-profit organisations can step in and fill a vital role. This seems to be happening for some neglected tropical diseases. Thus the orphan drug designation could be a useful tool to generate drug development in this arena. Read the resume.
 


 
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
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Editorial Board: Ségolène Aymé, Catherine Berens, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
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