1 October 2008 print
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Editorial
 
Europe’s health care challenges: rare diseases and orphan drugs in the limelight
 
The first colloquium devoted to the theme of health care in Europe under the French presidency of the European Union took place on 10 September at the Sorbonne University in Paris, and sought to define and prioritise the medical, economic and political challenges facing European healthcare. The first topic to be debated concerned access to expensive medicinal products. While close to 80% of medications are available in less-expensive generic forms, new products coming on the market are often very costly, and destined for small populations of patients - the very definition of an orphan drug. Several points arose on this topic, such as how to evaluate the service these innovative products provide society and determine their legitimate value. The expensive innovative products coming onto the market also highlight and aggravate the inequities existing within the EU, as a number of countries simply cannot assume the cost of reimbursing such treatments for their citizens. Gilles Pajot, of health industry intelligence provider IMS Health, demonstrated that the prices demanded for new products are directly correlated to market size. The linearity of the relationship between market size and price for these medicines explains the often-misunderstood reasons for the high price of orphan medicines. Pr. Laurent Degos of the French National Health Authority (HAS) placed the responsibility for the high prices of innovative medicines on the orphan drug regulation. However, this regulation does not impact the problematic of the consequences of small population samples on innovation costs. The representatives of the British health authority (NICE) and German equivalent (IQWIG) presented their decision process systems concerning reimbursement of innovative products. A solution may be to limit the collective resources for these products, which usually benefit the most gravely ill patients. However, such a highly political decision would require the involvement of all concerned parties.


The rest of the day was devoted to neglected diseases affecting developing countries, and European competitiveness in the international health industry. The colloquium was organised by the French Association of Pharmaceutical Laboratories (LEEM) and by IMS Health.
 


 
National & International Policy Developments
 
Bulgaria announces approval of national programme for rare diseases
 
On 9 September, the Bulgarian Ministry of Health announced its approval of a National Programme for Rare Diseases (including genetic diseases, congenital malformations and rare non-hereditary conditions). The programme, developed by leading specialists in the field, is designed to cover the period 2009-2013 and consists of nine priority actions. This initiative answers the long-standing need for a national policy regarding the prophylaxis, diagnosis and management of rare diseases in Bulgaria. It works within the framework of the European Commission recommendation that each EU member state develop a specific rare disease policy. The newly-approved programme is to include epidemiological studies, the creation of a rare disease registry, and support for six national reference centres. The programme also includes screening studies for pregnant women and newborns, to be conducted via the genetic laboratories of the Universities of Sofia, Pleven, Plovdiv, Varna, and Stara Zagora. Funds will be available for the kits, chemicals, and equipment needed for this action. The programme is to also include genetic counselling, and the dissemination of medical information on rare diseases to the general population. In the long term, it is believed that the rare disease health programme will prove economical, reducing future social and medical expenses. The programme must next receive official approval by the country's Council of Ministers.

On 16 September members of the Bulgarian National Alliance of People with Rare Diseases went ahead with a previously planned demonstration in front of the national parliament. The "Promises do not cure" remonstration was mounted in protest of governmental bureaucracy and policies, which the rare disease organisation claims prevent patients from accessing the medical treatments and care they need.
Consult the Bulgarian Ministry of Health announcement (in Bulgarian)

 
Japanese policy for rare disease care gives priority to specific illnesses
 
In response to a series of articles on the topic of rare diseases appearing in the 14 June issue of the Lancet, representatives from the Japanese Ministry of Health took pen to paper to describe Japanese policy vis-a-vis rare disease patients. Japan, in fact, predates all western countries in creating a programme specific to rare diseases. The National Programme on Rare and Intractable Diseases was launched in Japan in 1972. Whereas Japan uses prevalence rates similar to Europe to define a rare disease, they add one criterion to their disease definition that narrows the scope considerably in comparison to European or American definitions. Rare diseases in Japan are further defined as those illnesses having "no known cause" as well as no known cure. Some 130 diseases have been given priority status, including Behcet disease and amyotrophic lateral sclerosis. Forty-five of these have been given special status through which patients can register for a subsidy programme that encompasses in- and out-patient care as well as medicinal treatments. Furthermore, over 60 research groups are working holistically on projects relating to the 130 defined diseases. The Japanese Intractable Diseases Information Center, a website intended for professionals and patients, is available in Japanese and English languages and provides a detailed explanation of the rare disease care scheme currently operating as well as a list of the 45 diseases with priority status.
 
New website informs patients, parents and professionals on clinical trials in children
 

A new Internet website created in the USA serves patients, parents and professionals to better understand and access information concerning paediatric medicines and clinical trials. Created by the National Heart Lung and Blood Institute (NHLBI), in partnership with other National Institutes of Health (NIH) institutes, the site combines video and text to address some pertinent issues evolving from the new thinking on administering medicinal products for children that is resulting in clinical trials for paediatric populations of many diseases – including rare ones - both in the USA and in Europe. It is hoped that the new website will enable parents and paediatric patients to better understand the role of clinical trials and ultimately facilitate the consent process. The website addresses the major themes involved in paediatric clinical trials: why research is necessary in paediatric populations; benefits and disadvantages; what happens at the end of a study; rights of families; and much, much more.
Visit the Children & Clinical Studies website

 
England’s system for distributing rare cancer medications is not NICE
 
According to an audit by the Rarer Cancers Forum, the system of approving medicines for rare cancers in England is arbitrary, resulting in wide variations in patient access to treatment between different regions of the country. Accessibility to medicinal products is generally determined by guidance documents issued by NICE – the National Institute for Clinical Excellence. However, for many rare cancers, such guidelines do not exist. This puts the decision in the hands of individual primary care trusts (the agencies responsible for managing healthcare funding locally in England) which often do not have access to information and must rely on an “exceptional case” decision-making process. For rare cancers, the audit found that of 5,000 patients obliged to demonstrate ‘exceptionality’ in the period studied, 1,300 had their requests rejected. Some 3000 patients apply each year for “exceptional funding” for high-priced treatments, often to be used off-licence, and primarily for very advanced cancers. The most requested products include sunitinib (Sutent), erlotinib (Tarceva), cetuximab (Erbitux) and bortezomib (Velcade) – all of which have orphan designations in Europe or the USA. There is no nation-wide guidance on how to consistently reach exceptional-funding decisions, and this has resulted in an inequity throughout the land, with some primary care trusts approving all exceptional-funding applications and others systematically refusing identical requests. The report makes several recommendations to alleviate the current situation.
Consult the audit

 
Australia grants licence for human embryo cloning
 
Australia has granted its first licences permitting the creation of human embryos via cloning in order to derive human embryonic stem cell lines that can be used to research an array of disorders, including rare conditions. The country’s National Health and Medical Research Council has issued three licences to firm Sydney IVF. The licences permit the creation of embryos via somatic cell nuclear transfer, a technique that removes the DNA from the nucleus of an unfertilised egg and replaces it with the nucleus of an adult cell. A government press release states that successful cloning for research purposes “would be a world first, significantly contributing to the field of stem cell research”. Cloning for reproductive purposes remains strictly forbidden under the country’s Prohibition of Human Cloning for Reproduction Act.
 
Orphan drug research does not make the priority list of Italian funding scheme this year
 
Since 2005, orphan drug research in Italy has benefited from an innovative scheme that requires Italian pharmaceutical companies to donate 5% of their promotional expenditure to an independent research fund, which to date has targeted rare disease and orphan drug research, amongst other areas. In 2006, for example, some 30 independent research protocols in the area of rare diseases and orphan drugs were selected for funding by the Agenzia Italiana de Farmaco (AIFA) through this unique initiative. This year, however, rare disease and orphan drug research do not figure amongst the areas given priority. OrphaNews Europe hopes that orphan drug and rare disease research will be back on the AIFA priority list as soon as possible!
 
Other International News
 
US study reveals increased survival for paediatric blood cancer patients
 
A recent periodic analysis study published in the online edition of the Journal of the National Cancer Institute has determined that five- and ten-year survival rates continue to improve in children in the USA with haematology cancers. Patients under the age of 15 years with acute lymphoblastic leukaemia, acute non-lymphoblastic leukaemia or non-Hodgkin lymphoma all show increased long-term survival. Between 1990–1994 and 2000–2004, five- and 10-year survival increased from 80.2% to 87.5% and from 73.4% to 83.8%, respectively, for patients with acute lymphoblastic leukaemia. Meanwhile, survival increased from 41.9% to 59.9% and from 38.7% to 59.1%, respectively, for patients with acute non-lymphoblastic leukaemia, and from 76.6% to 87.7% and 73.0% to 86.9%, respectively, for patients with non-Hodgkin lymphoma. Advances in treatment are cited as the major contributing factor to the improved survival. However, in an editorial article accompanying the study, the authors (from the National Cancer Institute in Bethesda, MD) underscore the necessity of incorporating molecularly targeted therapies in order to further progress.
Consult the abstract

 
First Arab genome sequenced
 
A collaborative project between bioinformatics firm CLC bio, the Beijing Genomics Institute, and Saudi Biosciences has announced the sequencing of the first Arab genome. While no data from the sequencing has been made available, the news could be of interest to rare disease researchers due in part to the high number of rare genetic disorders in the population stemming from the not uncommon practice of inter-family marriage in many Arab countries. The sequencing of the first human genome in this population is part of a larger project aiming to sequence 100 Arab genomes by 2010. The project includes analysis and identification of the unique variants of the Arab genome in comparison with African, European and Asian genomes. Illumina’s Genome Analyzer platform was used to sequence the genome.
Consult the CLC bio press release

 
First Latin American Congress for Rare Diseases and Orphan Drugs raises visibility in the region
 
The very first conference dedicated to rare diseases took place in Buenos Aires, Argentina, in late March, bringing together scientists, health professionals, government, industry and patients to exchange knowledge and communicate needs. Organised by the Geiser Foundation (featured in the 14 June 2007 issue of OrphaNews Europe) and member organisations, the three-day event was attended by over 600 stakeholders from the region, and also included the participation of key international experts from the USA and Europe. Nurturing international collaboration in order to share resources and expertise is essential to developing quality heath-care for rare disease patients in Latin America. The conference broached all the topics relevant to rare diseases: diagnostics, research, treatment access, and the role of patient organisations. The Geiser Foundation unveiled a project to create an organisation modelled after EPPOSI, the European Platform for Patient Organisations, Science and Industry. A summary article of the conference (available on the GEISER website in English and Spanish languages) reports that media coverage of the congress served to bring awareness to the general public: the fact that some three million people in Argentina alone suffer from a rare disease created a stir in the area.
 


 
Ethical, Legal & Social Issues
 
Consert project to hold ethics symposium on gene therapy for inherited conditions
 
The Ethics of Gene Therapy of Inherited Diseases symposium, in the framework of the FP6-supported Consert project, will take place on 13 November in conjunction with the Annual Congress of the European Society of Gene and Cell Therapy meeting in Brugges. Curing severe genetic disorders via the genetic modification of somatic cells has been considered a great challenge for some decades. Clinical studies show efficacy and advantage for some illnesses compared to existing therapies, but serious risks have also been revealed. Planning research in this field of molecular medicine and deciding on the next steps presents not only a difficult medical task but also raises ethical questions. Ethical decision-making takes into account what has been learned from clinics and laboratories where safety research is conducted, and also considers what still needs to be learned. The ethics of gene therapy is striving to find a happy medium between false scepticism and excessive optimism. For further information
 
EuroGentest creates quality-controlled information leaflets for patients available in several languages
 
In response to a study that revealed a lack of consistent, quality written information for patients and their families on topics relating to genetic testing, EU-funded Network of Excellence EuroGentest, in collaboration with genetics professionals and an expert group of European patient representatives, has produced a series of leaflets. The leaflets, freely available on the EuroGentest website and to be distributed to genetic test centres throughout Europe, are designed to be clear and simple, and to foster patient understanding and decision making in relation to genetic testing. Eleven leaflets have been produced on the following subjects: Amniocentesis Test; Chromosome Translocations; Chromosome Changes; Chorionic Villus Sampling (CVS) Test; Dominant Inheritance; Frequently Asked Questions; Genetic Glossary; Recessive Inheritance; Some Information About Your Genetic Appointment; What is a Genetic Test?; and X Linked Inheritance. EuroGentest undertook a series of crosschecks to verify that the often complex information contained in the leaflets is presented in a manner that is easily understandable, thorough and current. The leaflets, already available in 13 languages, are destined to be translated into a total of 20 languages by the end of 2009. EuroGentest is planning to develop another batch of leaflets that will address some of the psychosocial issues related to genetic testing.
 
Charity study revealing increasing rate of Down syndrome births questions current screening policies
 
A study in the UK conducted by charity Downsed International finds that the rate of births of babies with Down syndrome has increased some 25% in the last 15 years, despite advances in prenatal screening that permit detection of the disorder. The study also claims that both life expectancy and quality of life are increasing for people with Down syndrome, due largely to improved healthcare and more effective educational approaches. The authors of the report call into question the ethics of current screening practices in light of the percentage (between 1%-2%) of non-Down syndrome foetuses lost due to invasive testing procedures (namely, amniocentesis and chorionic villus sampling). The authors also suggest that the advances in managing the disorder that are contributing to a longer, higher-quality life could indicate that a debate is needed to determine whether research and practice policies need to “shift from prevention to improving care, education and support for a growing and ageing population”.
 
Will new genetic screening programme for newborns in India help manage diseases better?
 
The Times of India has reported that the Lok Nayak Hospital in New Delhi has launched a newborn molecular screening programme that has the capacity to test some 400 genetic disorders. The government initiative is being offered free of charge. While early diagnosis of some of the disorders being tested (G6PD deficiency, for example) can lead to improved outcome, many other diseases have no treatment available. Furthermore, a positive result for a given disorder does not necessarily mean that the patient will ever to develop the corresponding phenotype.
Consult the news article

 


 
Orphanet News
 
New Texts
 
New Orphanet Journal of Rare Diseases Publications
 
Gitelman syndrome

Mixed cryoglobulinemia

Centronuclear (myotubular) myopathy


 


 
New Syndromes
 
X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum caused by CASK mutations
 
The authors describe a previously unreported X-linked brain malformation syndrome caused by mutations of CASK, a multi-domain scaffolding protein that interacts with the transcription factor TBR1 and regulates expression of genes involved in cortical development such as RELN. All five affected individuals with CASK mutations had congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia, and severe mental retardation.
Read the PubMed abstract

 
Nat Genet ; Epub ahead of print ; 10 August 2008
 


 
New Genes
 
Familial neuroblastoma: identification of ALK as a major predisposition gene
 
Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here the authors show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. Their results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.
Read the PubMed abstract

 
Nature ; Epub ahead of print ; 24 August 2008
 
Williams syndrome: TRIM50 encodes an E3 ubiquitin ligase
 
Williams syndrome (WS) is a neurodevelopmental and multisystemic disease that results from hemizygosity of approximately 25 genes mapping to chromosomal region 7q11.23. The authors report the preliminary description of eight novel genes mapping within the WS critical region and/or its syntenic mouse region. Three of these genes, TRIM50, TRIM73 and TRIM74, belong to the TRIpartite motif gene family, members of which were shown to be associated with several human genetic diseases. Trim50 encodes an E3 ubiquitin ligase, opening the hypothesis that the ubiquitin-mediated proteasome pathway might be involved in the WS phenotype.
Read the PubMed abstract

 
Eur J Hum Genet ; 1038-1049 ; September 2008
 


 
Research in Action
 
Fundamental Research
 
Ollier disease: PTHR1 mutations result in receptor loss of function
 
PTHR1-signaling pathway is critical for the regulation of endochondral ossification. Thus, abnormalities in genes belonging to this pathway could potentially participate in the pathogenesis of Ollier disease/Maffucci syndrome, two developmental disorders defined by the presence of multiple enchondromas. A functionally deleterious mutation in PTHR1 (p.R150C) was identified in enchondromas from two of six unrelated patients with enchondromatosis. However, neither the p.R150C mutation (26 tumors) nor any other mutation in the PTHR1 gene (11 patients) could be identified in another study. To further define the role of PTHR1-signaling pathway in Ollier disease and Maffucci syndrome, the authors analyzed the coding sequences of four genes (PTHR1, IHH, PTHrP and GNAS1) in leucocyte and/or tumor DNA from 61 and 23 patients affected with Ollier disease or Maffucci syndrome, respectively. They identified three previously undescribed missense mutations in PTHR1 in patients with Ollier disease at the heterozygous state. These mutations were not found in DNA from 222 controls. These findings provide further support for the idea that heterozygous mutations in PTHR1 that impair receptor function participate in the pathogenesis of Ollier disease in some patients.
Read the PubMed abstract

 
Hum Mol Genet ; 2766-2775 ; 15 September 2008
 
Diamond-Blackfan anaemia: abnormalities of the large ribosomal subunit protein
 
Diamond-Blackfan anaemia (DBA) is an inherited bone marrow failure syndrome characterized by anaemia, congenital abnormalities, and cancer predisposition. Small ribosomal subunit genes RPS19, RPS24, and RPS17 and are mutated in approximately one-third of patients. The authors used a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray in the analysis of 2 DBA patients with chromosome 3q deletions to identify RPL35A as a potential DBA gene. Sequence analysis of a cohort of DBA probands confirmed involvement of RPL35A in DBA. These data support the hypothesis that DBA is primarily the result of altered ribosomal function.
Read the PubMed abstract

 
Blood ; 1582-1592 ; 1 September 2008
 
Dystonia-associated mutations cause premature degradation of torsinA protein and mislocalization to the nuclear envelope
 
The major cause for early-onset torsion dystonia (DYT1) is an in-frame 3 bp deletion in the torsinA gene resulting in the loss of a glutamate residue at position 302 or 303 (torsinA DeltaE). In addition, an 18 bp deletion in the torsinA gene resulting in the loss of residues 323-328 (torsinA Delta323-8) has also been associated with dystonia. In this study, the findings suggest that torsinA mutation-induced premature degradation may contribute to the pathogenesis of dystonia via a loss-of-function mechanism and underscore the importance of both the proteasome and macroautophagy in the clearance of dystonia-associated torsinA mutant proteins.
Read the PubMed abstract

 
Hum Mol Genet ; 2712-2722 ; 1 September 2008
 
Huntington disease: accumulation of N-terminal mutant huntingtin in animal models implicated as a pathogenic mechanism
 
A number of mouse models expressing mutant huntingtin (htt) with an expanded polyglutamine (polyQ) domain are useful for studying the pathogenesis of Huntington disease (HD) and identifying appropriate therapies. However, these models exhibit neurological phenotypes that differ in their severity and nature. Understanding how transgenic htt leads to variable neuropathology in animal models would shed light on the pathogenesis of HD and help to choose HD models for investigation. By comparing the expression of mutant htt at the transcriptional and protein levels in transgenic mice expressing N-terminal or full-length mutant htt, the authors found that the accumulation and aggregation of mutant htt in the brain is determined by htt context. HD mouse models demonstrating more severe phenotypes show earlier accumulation of N-terminal mutant htt fragments, which leads to the formation of htt aggregates that are primarily present in neuronal nuclei and processes, as well as glial cells. Similarly, transgenic monkeys expressing exon-1 htt with a 147-glutamine repeat (147Q) died early and showed abundant neuropil aggregates in swelling neuronal processes. Fractionation of HD150Q knock-in mice brains revealed an age-dependent accumulation of N-terminal mutant htt fragments in the nucleus and synaptosomes, and this accumulation was most pronounced in the striatum due to decreased proteasomal activity.
Read the PubMed abstract

 
Hum Mol Genet ; 2738-2751 ; 1 September 2008
 
Hodgkin lymphoma cell lines: vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death
 
Epigenetic changes have been implicated in silencing several B-cell genes in Hodgkin and Reed-Sternberg cells (HRS) of Hodgkin lymphoma (HL), and this mechanism has been proposed to promote HRS survival and escape from immunosurveillance. However, the molecular and functional consequences of histone deacetylase (HDAC) inhibition in HL have not been previously described. In this study, the authors report that the HDAC inhibitor vorinostat induced p21 expression and decreased Bcl-xL levels causing cell-cycle arrest and apoptosis. Furthermore, vorinostat inhibited STAT6 phosphorylation and decreased its mRNA levels in a dose- and time-dependent manner, which was associated with a decrease in the expression and secretion of Thymus and Activation-Regulated Chemokine (TARC/CCL17) and interleukin (IL)-5 and an increase in IP-10 levels. Collectively, these data suggest that pharmacologic HDAC inhibition in HL may induce favorable antitumor activity by a direct antiproliferative effect on HRS cells, and possibly by an immune mediated effect by altering cytokine and chemokines secretion in the microenvironment.
Read the PubMed abstract

 
Blood ; 1424-1433 ; 15 August 2008
 
Pontocerebellar hypoplasia: tRNA splicing endonuclease mutations at cause
 
Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, the authors identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. These findings point to RNA processing as a new basic cellular impairment in neurological disorders.
Read the PubMed abstract

 
Nat Genet ; Epub ahead of print ; 17 August 2008
 
Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by microdeletions on chromosome 21q
 
Several lines of evidence support the presence of dosage-sensitive genes on chromosome 21 that regulate leukemogenesis and hematopoiesis. The authors report a detailed clinical and molecular characterisation of 3 patients with chronic thrombocytopenia caused by distinct constitutional microdeletions involving chromosomal region 21q22.12. The patients exhibited growth restriction, dysmorphic features, and developmental delays. One patient developed acute myelogenous leukemia (AML) at 6 years of age. All 3 deletions included the RUNX1, CLIC6, DSCR, and KCNE1 genes. The authors recommend that children with syndromic thrombocytopenia have clinical array-comparative genomic hybridisation analysis and appropriate cytogenetic studies to facilitate a definitive diagnosis.
Read the PubMed abstract

 
Blood ; 1042-1047 ; 15 August 2008
 
Churg-Strauss syndrome: variations of the interleukin-10 gene associated with antineutrophil cytoplasmic antibody-negative form
 
Wegener granulomatosis (WG) and Churg-Strauss syndrome (CSS) belong to the heterogeneous group of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Current understanding of their pathogenesis and genetic background is limited. Expression levels of interleukin-10 (IL-10), a potent and pleiotropic cytokine, are largely determined by variations in the gene encoding the IL-10 precursor. This study was undertaken to determine the impact of IL10 polymorphisms on the pathogenesis of both WG and CSS in large cohorts. Three single-nucleotide polymorphisms (SNPs) tagging the promoter haplotypes of the IL10 gene (IL10 -3575, IL10 -1082, and IL10 -592) were analyzed in 403 patients with WG and 103 patients with CSS as well as 507 matched control subjects from Germany. In addition, 3 informative SNPs in other parts of IL10 were genotyped. None of the markers or their haplotypes was associated with WG or any of its subgroups classified according to ANCA status, sex, or presence of further WG genetic risk factors. In contrast, the IL10 -3575/-1082/-592 TAC haplotype, part of the extended ancient haplotype IL10.2, was highly significantly associated with ANCA-negative CSS. These findings challenge those from previous studies of IL10 in WG and provide further evidence that CSS and WG have distinct genetic backgrounds.
Read the PubMed abstract

 
Arthritis Rheum ; 1839-1848 ; June 2008
 
Clinical Research
 
Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes: the RECQL4 mutation spectrum
 
Mutations in the RECQL4 gene can lead to three clinical phenotypes with overlapping features. All these syndromes, Rothmund-Thomson (RTS), RAPADILINO and Baller-Gerold (BGS), are characterised by growth retardation and radial defects, but RAPADILINO syndrome lacks the main dermal manifestation, poikiloderma, that is a hallmark feature in both RTS and BGS. It has been previously shown that RTS patients with RECQL4 mutations are at increased risk of osteosarcoma, but the precise incidence of cancer in RAPADILINO and BGS has not been determined. Here, the authors report that RAPADILINO patients identified as carriers of the c.1390+2delT mutation are at increased risk to develop lymphoma or osteosarcoma (6 out of 15 patients). This study also summarises all the published RECQL4 mutations and their associated cancer cases and provide an update of 14 novel RECQL4 mutations with accompanying clinical data.
Read the PubMed abstract

 
Eur J Hum Genet ; Epub ahead of print ; 20 August 2008
 
Autoimmune hepatitis: evaluation of risk factors in the development of hepatocellular carcinoma
 
Hepatocellular carcinoma (HCC) has traditionally been considered a rare complication of cirrhosis secondary to autoimmune hepatitis (AIH), yet the true incidence remains unknown. Consequently, some professional guidelines do not mandate routine surveillance for HCC in this condition. This study evaluates the rate at which HCC develops among a large, prospectively obtained cohort of patients with AIH at a single centre. HCC was discovered in 15 of 243 patients with AIH, all of whom had type 1 AIH. HCC occurred in the same proportion of females as males, 6.1% versus 6.4%. HCC occurred more frequently in patients who had cirrhosis at presentation or who had a variceal bleed as the index presentation of AIH. The median duration from time of confirmed cirrhosis to a diagnosis of HCC was 102.5 months. Median survival in patients whose HCC was diagnosed on surveillance was 19 months compared with 2 months for patients presenting symptomatically.
Read the PubMed abstract

 
Hepatology ; 863-870 ; September 2008
 
Huntington disease: long-term outcome of presymptomatic testing
 
This study on long-term outcome of presymptomatic testing for Huntington disease compares the psychological well-being and social adjustment of carriers and non-carriers of the mutation, and identifies psychological determinants to improve care/support of testees. The authors performed a cross-sectional study of 351 persons who underwent presymptomatic testing. Those who had motor signs were excluded from the comparison of asymptomatic carrier and non-carriers. A structured interview including five self-report scales and the MINI (Mini International Neuropsychiatric Inventory) was proposed to detect a psychopathology or problem with social adjustment. The authors interviewed 119 testees, 62 non-carriers and 57 carriers after a mean delay of 3.7 years after their result. Depression was frequent in asymptomatic carriers (58%). Interestingly, the self reported impact of the test showed that 27% of non-carriers did not cope well with a favourable result, and a significant percentage of non-carriers (24%) were depressed during follow-up. Psychological support is necessary for all testees regardless of the result of their presymptomatic test, because psychiatric care is often needed by both carriers and non-carriers.
Read the PubMed abstract

 
Eur J Hum Genet ; Epub ahead of print ; 20 August 2008
 
Congenital central hypoventilation syndrome: diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities
 
Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, the authors used diffusion tensor imaging-based measures in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.
Read the PubMed abstract

 
Pediatr Res ; 275-280 ; September 2008
 
Recessive dystrophic epidermolysis bullosa: the potential of fibroblast cell therapy
 
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin-blistering disorder caused by mutations in the COL7A1 gene that lead to reduced type-VII collagen and defective anchoring fibrils at the dermal-epidermal junction (DEJ). Presently there are no effective treatments for this disorder. Recent mouse studies have shown that intradermal injections of normal human fibroblasts can generate new human type-VII collagen and anchoring fibrils at the DEJ. To assess potential clinical benefits in humans, the authors gave single intradermal injections of allogeneic fibroblasts to five subjects with RDEB. They noted increased type-VII collagen at the DEJ at 2 weeks and at 3 months following injection and increased anchoring fibrils, although none of these had normal morphology. No adverse effects, clinical or immunopathologic, were noted. The major effect of allogeneic fibroblasts seems to be to increase the recipients' own COL7A1 mRNA levels with greater deposition of mutant type-VII collagen at the DEJ and formation of additional rudimentary anchoring fibrils. Nevertheless, this mutant protein may be partially functional and capable of increasing adhesion at the DEJ. This is the first study demonstrating that intradermal injections of allogeneic fibroblasts have therapeutic potential in human subjects with RDEB.
Read the PubMed abstract

 
J Invest Dermatol ; 2179-2189 ; September 2008
 
Chronic immune thrombocytopenic purpura: phase 2 trial measures rituximab efficacy and safety in adult splenectomy candidates
 
A multicenter, prospective, open-label, single-arm, phase 2 trial was conducted to assess rituximab safety and efficacy in adult splenectomy candidates with chronic immune thrombocytopenic purpura (ITP). Sixty patients with chronic ITP and platelet counts less than 30 x 10(9)/L received a weekly intravenous infusion of rituximab (375 mg/m(2)) for 4 weeks. All other ITP treatments were stopped. A good response was defined as a platelet count 50 x 10(9)/L or more, with at least a doubling of the initial value at 1 and 2 years after the first rituximab infusion. Sixteen patients experienced transient side effects that necessitated treatment discontinuation for only 1. Good 1-year responses were obtained in 40% of the patients. At 2 years, 33.3% had good responses and 6.7% had sustained platelet counts of 30 x 10(9)/L or more without treatment. Thirty-six patients failed to respond; 25 underwent splenectomy. Based on these results, rituximab was an apparently safe and effective splenectomy-avoiding option in some adults with chronic ITP.
Read the PubMed abstract

 
Blood ; 999-1004 ; 15 August 2008
 
Juvenile idiopathic arthritis: a longitudinal analysis of physical functional disability
 
This study describes the longitudinal course of physical functioning in children with juvenile idiopathic arthritis (JIA) and identifies predictors of long-term functional impairment. Between January 1987 and December 2002, 227 patients had two or more functional ability questionnaires completed by a parent. At each questionnaire administration, patients were assigned to one of three functional disability states (1 = no disability; 2 = mild to moderate disability; 3 = severe disability), based on their functional ability score. Despite patient variability in the course of physical functioning, the following three longitudinal patterns were observed: (1) a stable state of disability throughout the entire study period, with continued absence of disability in 27.8% of patients and persistently moderate disability in 3.5% of patients; (2) a steady improvement (22.9% of patients) or deterioration (5.7% of patients) in disability over time; (3) a fluctuating course of disability, with deterioration and improvement (40.1% of patients). Younger age at disease onset and a greater restricted joint count were the strongest predictors of long-term functional impairment. A wide within-patient and between-patient variability in the longitudinal course of functional disability was found.
Read the PubMed abstract

 
Ann Rheum Dis ; 1159-1164 ; August 2008
 
Juvenile idiopathic arthritis: adverse events of tumour necrosis factor alpha blockade in a long-term study
 
This study reports adverse events (AEs) seen in a large cohort of patients with juvenile idiopathic arthritis (JIA) treated with tumour necrosis factor (TNF) alpha blockers (infliximab and etanercept). 163 patients with JIA treated with infliximab or etanercept at the Paediatric Rheumatologic Centre of the G Pini Institute (Milan, Italy) from November 1999 to February 2006, were enrolled in an open, single-centre, long-term prospective study. A total of 45 patients (32 infliximab, 13 etanercept) failed to respond to or did not tolerate the first therapy and switched to a second one. In all, 208 treatments were performed. A total of 71 AEs occurred in 51 patients on infliximab and led to discontinuation in 26; 133 AEs occurred in 69 patients on etanercept and led to discontinuation in 18. In all, anti-TNFalpha agents infliximab and etanercept were well tolerated and safe, and were associated with only few serious, but all reversible, AEs. However, such inhibitors are associated with various and numerous AEs and children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFalpha therapy as much as possible.
Read the PubMed abstract

 
Ann Rheum Dis ; 1145-1152 ; August 2008
 
Fibrodysplasia ossificans progressiva: rare disease provides insights useful to more common disorders
 
Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic disorder of extensive and debilitating extra-skeletal bone formation. While the challenges of investigating a rare condition are many, the potential benefits are also great - not only for the specific disease under investigation, but also for the unique perspective on how cells normally function and the mechanisms that underlie more common disorders. This review illustrates some of the many insights gained by studying FOP.
Read the PubMed abstract

 
Bone ; 427-433 ; September 2008
 
Kawasaki disease: a review of the disorder, diagnostics and treatment
 
Kawasaki disease is a febrile systemic vasculitis complicated by coronary and peripheral arterial aneurysms in 20% to 35% of untreated patients. This review article presents the characteristics of the disease and reviews current diagnostics and treatments.
Read the PubMed abstract

 
Circulation ; e110-e112 ; 12 August 2008
 
Tuberous sclerosis: increasing understanding of molecular abnormalities may improve management
 
Tuberous sclerosis is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. The affected genes are TSC1 and TSC2, encoding hamartin and tuberin respectively. The hamartin-tuberin complex inhibits the mammalian-target-of-rapamycin pathway, which controls cell growth and proliferation. Variations in the distribution, number, size, and location of lesions cause the clinical syndrome to vary, even between relatives. Most features of tuberous sclerosis become evident only in childhood after 3 years of age, limiting their usefulness for early diagnosis. Identification of patients at risk for severe manifestations is crucial. Increasing understanding of the molecular abnormalities caused by tuberous sclerosis may enable improved management of this disease.
Read the PubMed abstract

 
Lancet ; 657-668 ; 23 August 2008
 
Marfan syndrome: report on research, treatment and patient management
 
Marfan syndrome is characterised mainly by musculoskeletal (dolichostenomelia, arachnodactyly, joint hypermobility, spinal involvement, acetabulum protrusion, thoracic skeletal involvement), ocular (dislocated lens, axial myopia) and cardiac anomalies. This report presents an overview of the disease, current treatment strategies, and the latest recommendations for patient management.
Read the PubMed abstract

 
Circulation ; 785-791 ; 12 August 2008
 
Therapeutic Approaches
 
Juvenile rheumatoid arthritis: adalimumab with or without methotrexate
 
Tumour necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis. The authors evaluate the efficacy and safety of adalimumab, a fully human monoclonal anti-TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis.74% of patients not receiving methotrexate and 94% of those receiving methotrexate had an ACR Pedi 30 response at week 16 and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flares occurred in 43% of those receiving adalimumab and 71% of those receiving placebo. Among patients receiving methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of those receiving placebo. At 48 weeks, the percentages of patients treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for those receiving adalimumab than for those receiving placebo; the differences between patients not treated with methotrexate who received adalimumab and those who received placebo were not significant. Serious adverse events possibly related to adalimumab occurred in 14 patients. Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis.
Read the PubMed abstract

 
NEJM ; 810-820 ; 21 Aug 2008
 
Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates
 
Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of severe juvenile osteoporosis and congenital blindness, due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Approximately fifty cases of OPPG have been reported. The authors report 9 new cases of OPPG, in three related nuclear families of Conservative Mennonites in Pennsylvania. All 9 children with OPPG were blind and had osteoporosis. Four of six parents had low bone mineral density (BMD) or osteoporosis; 2 were normal. Sequence analysis from genomic DNA revealed homozygosity for a nonsense mutation of exon 6 of LRP5 (W425X) in four OPPG cases tested in families A and C. In family B, OPPG cases were compound heterozygotes for the exon 6 W425X LRP5 mutation and a second exon 6 mutation (T409A); bone phenotype was milder than in family A. Neither of these mutations was present in an unrelated normal. The four treated OPPG patients all responded to bisphosphonates (duration 1.5-6.5 years) with improvement in Z-scores.
Read the PubMed abstract

 
Bone ; 584-590 ; September 2008
 


 
Patient Management and Therapy
 
Fabry disease: enzyme replacement therapy with agalsidase alfa in a cohort of Italian patients
 
Fabry disease (FD) is a rare X-linked disorder caused by lysosomal storage of several glycosphingolipids, affecting virtually all organs and systems. Enzyme replacement therapy (ERT) for FD has been available since 2001. Due to the highly variable nature of clinical manifestations in patients with FD, it is very difficult to assess disease progression and the effects of therapy. The authors used the Mainz Severity Score Index (MSSI) as a measure of disease severity to study the effects of ERT in a population of 30 patients treated with agalsidase alfa for a median of 2.9 years. The MSSI captures the correlation between disease severity and both gender and age. Furthermore, after at least 1 year of ERT, total MSSI scores were significantly lower than those at baseline, suggesting a marked clinical improvement under ERT.
Read the PubMed abstract

 
Clin Genet ; Epub ahead of print ; 28 April 2008
 


 
Orphan Drugs
 
Eleven EMEA orphan drug designations for September
 

The COMP (Committee for Orphan Medicinal Products) adopted the following eleven positive opinions on orphan medicinal product designation at its September meeting for the treatment of:

- chronic idiopathic myelofibrosis
- alpha-sarcoglycanopathy
- spinal cord injury (2 products)
- propionic acidaemia
- isovaleric acidaemia
- methylmalonic acidaemia
- cystinosis
- corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns
- chronic lymphocytic leukaemia
- mucopolysaccharidosis III, type A (Sanfilippo A syndrome)
Consult the European Registry for Orphan designations
Consult the Orphanet list of orphan drugs authorised for marketing in Europe

 
Cystic fibrosis orphan drug scorecard: 0 (marketed treatments) to 27 (designations)
 
The Guideline on the Clinical Development of Medicinal Products for the Treatment of Cystic Fibrosis was recently published by the European Medicines Agency and is open for public consultation and comments until 30 November. Although a large of orphan designations have been issued for the disease (27 to date), no product has yet been brought to market. The guideline was developed to provide counsel on the clinical development of medicinal products due to the need for new compounds for treating pulmonary disease and infections and exocrine pancreatic insufficiency and associated malnutrition. As the guidelines iterate, these conditions affect more than 90% of patients with cystic fibrosis and are the major factors in the morbidity and mortality of the disease.
 
FDA approves treatment for chronic inflammatory demyelinating polyneuropathy
 
The U.S. Food and Drug Administration has approved Gamunex, an immune globulin product, for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), a rare autoimmune disorder characterized by progressive weakness and impaired sensory function in the legs and arms. Gamunex is manufactured by Talecris Biotherapeutics Inc. of Research Triangle Park, N.C.
 


 
What's on Where?
 
European Research Conference in Paediatric Neurology
 
Date: 3-4 October 2008
Venue: Tubingen, Germany

The meeting enables researchers to meet colleagues in the same field in order to facilitate collaboration, and to foster the building of research networks. Most of the meeting is therefore reserved for discussion and interaction in the following working groups: Neurometabolic diseases, Autoimmune diseases, Neonatal Neurology, Neurodegeneration and Neuroprotection, Epilepsy, Neuromuscular Diseases, Genetics, Developmental Neurology, and Infection-related inflammatory CNS diseases.
For further details

 
Rare Diseases Warsaw 2008: MPS and Rare Diseases Conference
 
Date: 3-5 October 2008
Venue: Warsaw, Poland

The purpose of the conference is to introduce aspects of treatment and specialised medical care for rare genetic diseases and to strengthen cooperation and the exchange of experience between scientific environments and government institutions, as well as patient associations from Central and Eastern Europe.
For further details

 
International Conference on Thalassaemia and Haemoglobinopathies
 
Date: 8-11 October 2008
Venue: Singapore

The 11th International Conference on Thalassaemia and Haemoglobinopathies and the 13th International Thalassaemia TIF Conference for Thalassaemia Patients and Parents. "Equal Access to Quality Medical Care for Every Patient with Thalassaemia" is the theme of this year's conferences.
For further details

 
EuroGentest Workshop: Fulfilling the Requirements of ISO 15 189 - Management Review, IQC and EQA
 
Date: 9-10 October 2008
Venue: Berlin, Germany

This workshop will permit attendees to attain an in-depth understanding of what the ISO 15189 standard requires and how to translate these requirements into practical measures in the laboratory.
For further details

 
International Conference on Genetic and Molecular Basis of Rare Kidney Disorders
 
Date: 9-11 October 2008
Venue: Bergamo, Italy

This conference will bring together research geneticists, nephrologists, clinicians and experts from related specialties to discuss the latest findings on and around the core themes of rare kidney diseases. The speakers will cover a varieties of topics: glomerular filter structure and function in health and diseased states, genetic basis of glomerular diseases (focal and segmental glomerulosclerosis, hematuric syndromes, dense deposit disease), inherited disorders of tubular function, and renal developmental disorders. The Conference Keynote lecture will be delivered by Nobel Laureate professor Peter Agre, who will discuss the impact that the discovery of aquaporins has had on the understanding of physiologic and pathologic states.
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

 
11th Epilepsy & Society Conference
 
Date: 15-17 October 2008
Venue: Marseilles, France

The theme of the conference is "Active Life and Epilepsy" focusing on different aspects of achieving goals and a better quality of life. In addition to prominent medical experts in the field of epilepsy, speakers will include those working in epilepsy support and people with experience of epilepsy.
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

Registration is open 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

 
Annual Meeting of the Italian Network for Promotion of Folic Acid and Prevention of Congenital Defects
 
Date: 17 October 2008
Venue: Rome, Italy

Current debate pivots on how to potentiate actions towards periconceptional supplementation, as well as on possible complementary strategies, such as nutritional education as well as generalised or facultative fortification. The principal issues discussed in this meeting relate to the risk-benefit analysis of prevention approaches using folic acid.
For further details

 
Dystonia Europe 2008
 
Date: 17-19 October 2008
Venue: Hamburg, Germany

This conference will provide a forum for discussion of the latest developments in clinical features, treatment and research of dystonia, with presentations from a broad range of leading experts from Europe and North America.
For further information

 
First Congress of the African Society for Immunodeficiencies
 
Date: 30 October-1 November 2008
Venue: Casablanca, Morocco

Organised by the African Society for Primary Immunodeficiencies in conjunction with the Moroccan Societies for Paediatrics and for Haematologies, themes to be explored during this congress include primary immunodeficiencies (PIDS) and the skin; PIDs and the lungs; PIDs and the adult patient; PIDS and lymphomas; PIDs and nutrition; and PIDs and vaccines.
For further information

 
ESF-UB Conference in Biomedicine: Biobanks
 
Date: 1-6 November 2008
Venue: Sant Feliu de Guixols, Spain

The ESF-UB Conference on Biobanks will be focused on providing an open forum of discussion on all aspects involved in the governance, management and use of human biobanks, technical solutions, ethical, legal, and social aspects, also providing participants with a broad overview of the existing models of biobanks and the international initiatives on population-based and disease-oriented biobanks. A limited number of grants are available for young researchers to cover the conference fee and possibly part of the travel costs.
For further information

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

Details to follow shortly.
For further information

 
The Ethics of Gene Therapy of Inherited Diseases
 
Date: 13 November 2008
Venue: Brugges, Belgium

Considers ethical perspectives of gene therapy and risk management, amongst other related topics .
For further information

 
International Symposium on Rare Diseases: Inherited Neuromuscular Diseases: Translation from Pathomechanisms to Therapies
 
Date: 16-18 November 2008
Venue: Valencia, Spain

The symposium will permit exploration of the state-of–the-art of neuromuscular diseases as a whole, including muscular dystrophies, mitochondrial disorders, peripheral neuropathies, spinal muscular atrophy, motoneurone disease and Friedreich ataxia, and will explore pathogenic mechanisms and molecular targets for the different diseases, as a forum for discussion of the rational basis of the new therapeutic approaches.
For further information

 
From Cardiac Remodelling to Biotherapies: Homage to Ketty Schwartz
 
Date: 29 November 2008
Venue: Paris, France

The programme will include cardiac phenotype and remodelling in cardiopathies; genetics and pathophysiology of cardiac diseases; and therapies of cardiac and skeletal muscle diseases.
For further information

 
EuroGentest Workshop: Validation of Diagnostic Tests in Clinical Molecular Genetics
 
Date: 8-9 January 2009
Venue: Prague, Czech Republic

Genetic tests must be validated before diagnostic use to ensure that they perform according to the laboratory's requirements, and test validation is a formal requirement of many accreditation standards including ISO 15189. This workshop will examine the validation requirements of ISO 15189 and address practical ways of meeting them in the laboratory.
For further information

 
Molecular Mechanisms of Neurodegeneration
 
Date: 8-10 May 2009
Venue: Milan, Italy

Addressing the most important issues involved in protein toxicity in neurons, providing participants with updated information that could be useful to researchers in the field of neurodegenerative disorders.9.
For further information

 
7th World Congress on Melanoma
 
Date: 12-16 May 2009
Venue: Vienna, Austria

A joint meeting with the 5th Congress of the European Association of Dermato-Oncology. Clinicians and researchers will focus on the state of the art in prevention, recognition, and treatment of cutaneous neoplasms covering melanoma and non melanoma skin cancer as well as lymphomas and rare skin tumours. Deadline for submission of abstracts: 31 January, 2009.
For further information

 
8th Balkan Meeting on Human Genetics
 
Date: 14-18 May 2009
Venue: Cavtat, Croatia

"Rare diseases – public policy, research, diagnosis and management" is one of the topics featured in this conference. Deadline to submit an abstract is 20 January 2009.
For further information

 
12th International Congress on Neuronal Ceroid Lipofuscinoses
 
Date: 3-6 June 2009
Venue: Hamburg, Germany

The aim of this meeting is to facilitate and speed up exchange between expert scientists and physicians, but also to confront young researchers with the challenges of the largest group of degenerative brain diseases in young people. Deadline for submission of abstracts: 28 February, 2009.
For further information

 


 
Press & Publications
 
Another rare disease study contributes to more common disorders… WAGR syndrome research adds weight to understanding obesity
 
A National Institutes of Health study of rare genetic disorder WAGR syndrome, published in the 28 August issue of the NEJM, is proving relevant to understanding the much more prevalent condition of obesity. The study examines the role of brain derived neurotrophic factor (BDNF) in WAGR syndrome, a rare disorder with an estimated prevalence of 1 in 500,000 and which is characterised by Wilms tumour, aniridia, genitourinary anomalies, and mental retardation. BDNF is involved in long-term memory and also plays a role in the regulation of appetite. In studying a subgroup of WAGR children and adult patients with hyperphagia and obesity, the researchers found BDNF haploinsufficiency associated with lower levels of serum BDNF and with childhood-onset obesity. The study suggests that BDNF may thus be important for energy homeostasis in humans. In a related press release, Duane Alexander, M.D., director of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development pronounced the findings “…a promising new lead in the search for biological pathways that contribute to obesity,” which may “…eventually lead to the development of new drugs to regulate appetite in people who have not had success with other treatments.”
Read the PubMed abstract

 


 
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)
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Editor: Louise Taylor
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