21 February 2007 print
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A welcome initiative for the French Rare Disease community:

A Foundation for Pharmacists in France committed to RD information and research

A major new arm in the combat against rare diseases is about to join the European arena. The creation of the Fondation des Pharmaciens de France was announced this month by one of its major supporters, the FSPF (France’s largest pharmaceutical trade union). The Foundation is to represent and support France’s estimated 4 million rare disease patients. The project involves circulating to all local pharmacies the information on where and how to find information on rare diseases. Other aims include the development of clinical research into orphan pathologies and the improvement of knowledge on RDs through the creation of a patients’ observatory.

The Foundation will be officially created once its recently launched fund-raising association has raised the necessary cash (800 000 €). One novel fund-raising idea already put into action has been to produce a series of environment-friendly, cotton bags specially designed for the Foundation’s launch, bought by pharmacists and also distributed to patients when coming for treatment. Given that an average 180 patients are represented by each of France’s pharmacies, the idea is that this initiative will reach the parts many organisations fail to reach, through the highly localised coverage of the support offered. This important public health service means good news for patients all too often isolated with their disease, especially in more rural areas, regardless of their social or cultural background.

Read more about the Foundation (in French only).


Spotlight on...
Ducking the 'Doughnut Hole': the U.S. Rare Disease Health Cover Dilemma
Interview with Maria Hardin – Vice President, Patient Services, at NORD, the US National Organisation for Rare Diseases

OrphaNews: Can you briefly explain the social and political background which has created the difficult financial situation in which many RD patients in the USA now find themselves?

There are many reasons why over 48 million Americans, including many dealing with rare diseases, find themselves without any health insurance. During the earlier part of the 20th century, most major employers provided their employees with health benefits. Since then, and over the past 20 years, skyrocketing costs for insurance premiums have caused many employers to drop health care benefits, or are forcing employees to pay a larger share of the costs. Workers on the low end of the socio-economic spectrum (many of whom take home only a minimum wage) are either not offered any benefits at all by their employers, or if they are offered them, find their share of the premium costs is prohibitively expensive, and choose not to join a health plan.

The US Government (both Federal and State) is cutting back in health service provision even to the lowest economic level citizens. In the States, insurance companies can pick and choose whom they will insure. People with chronic, life-debilitating conditions (many of these are rare diseases) find themselves classified as “uninsurable” even if they manage to pay the high premiums. Some states have established “high risk” insurance pools for their citizens but costs are high, and there is usually a 6-12 month waiting period for “pre-existing” conditions to be covered.

OrphaNews: Tell us something about Medicare and its administration in the States

Medicare was established back in the 60’s during the Lyndon B. Johnson administration. Both elderly (65 years and older) as well as younger, permanently disabled citizens were automatically enrolled in Part A. This covers hospital costs. Part B covers medical services but requires payment of a nominal premium, and is optional. Prior to the passage of Medicare Part D, if citizens wanted drug coverage, they could purchase “Medi-Gap” insurance policies from the private insurance industry that had to be sanctioned by our Centers for Medicare and Medicaid Services, the government oversight agency for Medicare. The U.S. Congress passed the Medicare Modernization Act in late 2003, and for the first time, a prescription drug benefit was offered starting January 1, 2006.

OrphaNews: What exactly is the “doughnut hole” everyone from the RD community appears to be talking about your side of the Atlantic?

It is the “share-of-cost” incorporated into the new Medicare prescription drug benefit program to off-set the total cost of the drugs to the government’s budget. Unfortunately, it is positioned at the “front end” of the beneficiary’s coverage year. The beneficiary pays the first $250 for his/her Rx (called a deductible); then s/he must pay 25% of drug’s cost and the insurance plan pays the other 75% until a total of $2,250 has been reached. After that occurs, the beneficiary must pay 100% of the Rx cost until another $2,850 is spent. This is called THE DOUGHNUT HOLE! If one adds $2,250 + $2,850 = $5,100 at this point, the catastrophic level of coverage has been reached, and the beneficiary pays 5%/month/per needed drugs for the remainder of the calendar year. Then the cycle begins all over again. In 2007, the out-of-pocket cost to the beneficiary extends to $3,850 instead of $3,600. Monthly premium costs will rise also.

If a beneficiary can prove that his/her annual income is less than a specific dollar figure, special help is provided by the government and there is no deductible, no doughnut hole, and only a minimal co-payment for each Rx filled. Of the 13.2 million beneficiaries eligible for low-income assistance, 9.5 million are receiving the subsidy. However, there is an estimated 3.1 million eligible beneficiaries that are not receiving assistance.

Read the full NORD interview

National & International Policy Developments
Other European news
HAL: a new open archive initiative for international scientific production
Last month saw the launch of a new open archive initiative at INSERM, the French Health and Research Institute. This new service HAL-Inserm , comprising a platform able to give free, universal access to scientific articles, is already up and running and gives access to authors' versions of published articles. These articles can also be obtained from other open archives such as PubMed Central, which already contains authors’ versions of articles relating to work subsidised by the US National Institute of Health (NIH) and the UK’s Wellcome Trust.
This service, which could revolutionise the world of scientific publishing, is expected, over time, to guarantee international visibility for scientific work and long-term document protection.


Research in Action
EU project focus
AnEUploidy: a European project for understanding molecular trisomy and monosomy mechanisms

The European initiative, "AnEUploidy: Understanding Gene Dosage Imbalance in Human Health Using Genetics, Functional Genomics and Systems Biology", aims to develop research for a better comprehension of human aneuploidy mechanisms. Aneuploidy is a condition in which the number of chromosomes is abnormal due to extra or missing ones.

The project is led by Stylianos Antonarakis from the University of Geneva's Faculty of Medicine (UNIGE), and brings together 17 teams from 9 different countries (Switzerland, France, Germany, Italy, Spain, UK, Netherlands, Czech Republic, Israel). With 12 million euros funding from the European Union's 6th Framework Programme for Research and Technological Development*, this initiative is due to run for a four-year period.

* Contract no. LSHG-CT-2006-037627

Welcome to MYOAMP: a European project for Duchenne muscular dystrophy

The European project MYOAMP brings together cellular biologists, clinicians and biotech companies from 5 European countries (France, Italy, Sweden, Germany and the UK) to create the necessary conditions for the clarification of cell therapy in Duchenne muscular dystrophy. Four patient associations are also associated: French Muscular Dystrophy Association, the Duchenne Parent Project from France and the UK and the Monaco Muscular Dystrophy Associations. Set up by INSERM-Transfert, the project is financed by the European Union’s 6th R&D Framework Programme for Research and Technological Development* with total funds of 2.5 million euros for a 3-year period.

The project has 3 major objectives:

  • Combine cell therapy with exon skipping on myogenic stem cells and set up the necessary conditions for future clinical trials in Duchenne muscular dystrophy

  • Amplify human stem cells with myogenic potential in clinical conditions for an autologous cell therapy and produce amplication protocols that are standardised, reliable and secure

  • Hold a debate on regulatory aspects so that when the project comes to an end, the results and recommendations can be transferred to doctors or biotech companies for clinical application.

  • In Europe, more than 30,000 young people are affected by Duchenne muscular dystrophy (DMD). Of the muscular dystrophies, the DMD presents one of the most acute prognostics.

    * Contract no. LSHB-CT-2006-037479

    New diseases & syndromes
    Cardiomyopathy and renal anomalies in two brothers

    Leask et al. describe two brothers affected by a cardiomyopathy and malformations of the uro-genital tract. One of them also has a dysgenesis of the corpus callosum. With non-consanguineous parents not manifesting these symptoms, the two children appear to be affected by a new X-linked or autosomal recessive syndrome.
    Read the Pubmed abstract

    Clinical Dysmorphology ; 16(1):51-3 ; Jan 2007
    Phenotypical variability between a mother and her daughter affected by the same 4q34qter deletion

    Bendavid et al. describe two women, a mother and her daughter, both affected by the same 4q34qter deletion but manifesting different phenotypes. The mother has clinical signs previously described in the terminal deletions of a long arm of chromosome 4, (ie. a malformation of the lower limbs and a cardiac defect). In addition, at the age of 54, she has developed a rare gynaecological cancer: a serous carcinoma of the Fallopian tubes. The daughter has a congenital aplasia of the uterus and vagina, the first signs of the Mayer-Rokitansky-Kuster-Hauser syndrome. This syndrome had never before been associated with a terminal deletion of the long arm of chromosome 4.
    Read the Pubmed abstract

    European Journal of Human Genetics ; 50(1):66-72 ; Jan 2007
    New genes
    PALB2 : a third mutated gene in Fanconi Anemia and in familial forms of breast cancer
    Cancer du sein, forme familiale id=145 Anemie de Fanconi ID=634

    Fanconi anemia is a recessive disease characterised by a phenotypical heterogeneity including a bone marrow deficiency, variable malformations, a high cancer risk and a cellular hypersensitivity to DNA cross-linking agents. The mutations identified in 11 different genes are the cause of the chromosomal instability observed in the patients’ cells. Amongst these BRCA2 and BRIP1 genes, also known as FANCD1 et FANCJ, are also implicated in familial forms of breast cancer. This month, Nature Genetics has published three articles associating a third gene, PALB2, with Fanconi’s anemia and familial forms of breast cancer (however in the latter case, it involves monoallelic mutations).Xia et al.and Reis et al., inspired by a recent study demonstrating the existence of an interaction between proteins PALB2 and BRCA2, have identified biallelic mutations of PALB2 in a new complementation group of Fanconi anemia, subtype N. The cells belonging to one of the patients display an increased sensitivity to DNA cross-linking agents and are characterised by the absence of BRCA2 binding to chromatin. In addition, Rahman et al. have identified monoallelic mutations of PALB2 in familial forms of breast cancer. Researchers believe that these mutations, which have been observed in 10 out of 923 women with breast cancer and in 0 out of 1084 controls confer a 2.3 times higher risk of breast cancer.

    To read more about "Williams syndrome"
    To read more about "Fanconi anaemia"

    Nature Genetics ; 39(2):159-61 ; Feb 2007Nature Genetics ; 39(2):162-4 ; Feb 2007
    Nature Genetics ; 39(2):165-7 ; Feb 2007

    A loss of calcium channel type L function could be the cause of Brugada syndrome

    Brugada syndrome is characterised by ST-segment elevation by electrocardiogram in precordial derivations (V1 - V3) and a sensitivity to ventricular tachyarythmia which can lead to sudden death. These clinical signs may come from a loss of the SCN5A gene, coding the alpha subunit of the sodium cardiac channel. By direct analysis of the genes coding other ionic channels in 82 patients affected with Brugada Syndrome, the researchers have identified mutations in the CACNA1C and CACNB2 genes coding the subunits alpha1 and beta2b of the L-type calcium channel in 7 patients. These mutations, which are the observed cause of the observed Brugada syndrome, are also associated with an abnormally short QT interval.
    Read the Pubmed abstract

    To read more about "Brugada syndrome"

    Cell ; 115(4):442-9 ; Jan 30, 2007
    New fundamental research
    Regulatory aspects of the SHOX gene are absent in patients affected by dyschondrosteosis

    Dyschondrosteosis or Leri-Weill syndrome is characterised by skeletal deformations and short stature due to mutations in the SHOX gene. Certain patients do not have mutations in the coding sequence of the gene but manifest deletions in the chromosomal region downstream shox. After identifying eight phylogenetically well conserved non coding sequences, researchers showed that three of these have a cis-regulatory activity on shox in chickens (mice do not have this gene). The loss in the shox function or the deletion of regulatory elements situated at a distance from this gene therefore seem to lead to a similar phenotype in humans. More generally, the mutations in the distant regulatory sequences of the genes seem to represent an under-estimated cause in genetic disorders.
    Read the Pubmed article

    To read more about "Dyschondrosteosis"

    Human Molecular Genetics ; 15;16(2):210-22 ; Jan 2007
    Meckel-Gruber syndrome: the MKS1 and MKS3 proteins are necessary for ciliogenesis

    Meckel-Gruber syndrome is characterised by a renal cystic dysplasia, developmental anomalies in the central nervous system, a dysplasia of the bile ducts and hepatic cysts. The two genes MKS1 and MKS3 have recently been associated with this syndrome, however their role in the disease’s development has not been clarified. A team of British researchers have therefore attempted to analyse the localisation and function of proteins encoded by these genes. In accordance with the symptoms observed, the two proteins are expressed in the proximal renal tubules and in the biliary epithelial cells. Furthermore, these are necessary for the formation of primary cilium.
    Read the Pubmed abstract

    To read more about "Meckel syndrome"

    Human Molecular Genetics ; 15;16(2):173-86 ; Jan 2007
    Blackfan-Diamond anemia: ribosome biogenesis is altered in patients’ cells

    Blackfan-Diamond anemia is characterised by an aregenerative, often macrocytic anemia, associated with erythroblastopenia. The RPS19 gene, encoding the ribosomal protein S19 in the ribosomal subunit 40S, is frequently mutated, however the consequences of these mutations on the triggering of the disease remain unclear. Using interfering RNA in human cells, two independent teams demonstrated that RPS19 is necessary for the synthesis of ribosome ARN 18S and the maturation and cytoplasmic localisation of the ribosomal particles 40S. In accordance with these observations, the biogenesis of the ribosomes and the nucleolus organisation are disturbed in the cells of patients with mutations in the RPS19 gene. Due to their proliferation, the erythroblasts could be particularly sensitive to stress induced by a fault in the ribosomal biogenesis, thus explaining the specificity of the disease’s symptoms.
    Read the Pubmed abstract

    To read more about "Blackfan-Diamond disease"

    Blood ; 109(3):980-6 ; 1 Feb 2007Blood ; 109(3):1275-83 ; 1 Feb 2007
    Hypoalphalipoproteinemia corrected by an adenoviral vector in mice

    The quantity of high density lipoprotein, such as Apolipoprotein A-I (APOA1), is associated with a reduction of cardiovascular risks. In humans, the absence of APOA1 is a major cause of hypoalphalipoproteinemia and is associated with a high risk of atherosclerosis. In a murine model of the disease, researchers have shown that administration in the liver of a APOA1 transgene using an adenovirus dependant on an auxiliary virus, makes it possible to re-establish a high level of protein in the plasma and thus procures a long-term phenotype correction.
    Read the Pubmed abstract

    To read more about "Hypoalphalipoproteinemia, familial"

    Gene Ther. ; 14(3):191-202 ; Feb 2007
    The G6PT human transporter gene corrects metabolic and myeloid abnormalities in glycogen storage disease type Ib mice

    The glycogen storage disease type 1b is caused by a glucose-6-phosphate (G6PT) deficiency, a protein associated with the membrane of the endoplasmic reticulum and expressed in a ubiquitous way. The patients affected by this disease suffer from a de-regulation of the glucose homeostasia and a dysfonctioning of the bone marrow. In order to evaluate the possibility of gene therapy treatment, an American team has injected an adenovirus expressing the human G6PT transgene in a murine model of the disease. Researchers thereby observed a correction of metabolic and myeloid faults.
    Read the Pubmed abstract

    Gene Ther. ; 14(3):219-26 ; Feb 2007
    Intracellular QBP1 administration suppresses in drosophila the toxicity of proteins with glutamine expansions

    Certain neurodegenerative disorders are due to the expansion of glutamine repetitions which cause the aggregation of modified proteins thus inducing a neuronal toxicity. Recently, a Japanese team identified the QBP1 peptide for its capacity to interact with glutamine repetitions and thereby to suppress the toxicity of mutant proteins in drosophila. One of the obstacles to the perfecting of a molecular therapy by QBP1 is to target its action inside the cells. With this aim, Popiel et al. have established a fusion between QBP1 and the PTD peptide which gives the protein the capacity to cross the plasmic membrane. Introduced into the food of the drosophila, PTD-QBP1 successfully inhibits the toxicity of the mutant proteins ex vivo and in vivo.
    Read the Pubmed abstract

    Mol Ther. ; 15(2):303-9. ; Feb 2007
    Improvement of cognitive functions by enzymatic replacement therapy in mice with MPS 7

    Mucopolysaccharidosis type VII (MPS7) is caused by a beta-glucuronidase deficiency which leads to the accumulation of various glycosaminoglycanes in lysosomes. One of the difficulties in treating this disease by gene therapy is in the administering of replacement enzymes in the nervous central system. For this, American researchers injected recombinants virus into the striatum of a MPS 7 mouse, making the beta-glucuronidase expression possible. The expression of the enzyme in different parts of the brain was associated with a diminution in the lysosomal surcharge and in the improvement of the mouse’s cognitive functions.
    Read the Pubmed abstract

    To read more about "Mucopolysaccharidosis type 7"

    Mol Ther. ; 15(2):242-7 ; Feb 2007
    New clinical research
    Lentiviruses in the service of cellular therapy for Duchenne muscular dystrophy

    A possible approach for treating Duchenne muscular dystrophy is to transplant myogenic cells expressing dystrophin with the help of a transgene. Queneville et al. have used the lentiviral vector technology to express the dystrophin in mononuclear cells. After transplantation of the modified cells in mice, they observed the expression of the protein in muscular fibres. An identical approach has made possible the expression of micro-dystrophin in monkeys’ muscles transplanted one month earlier. In addition, the use of lentivirus has also been demonstrated efficient in restoring the expression of a dystrophin modified by exon skipping in patients’ myoblasts.
    Read the Pubmed abstract

    To read more about "Muscular dystrophy, Duchenne and Becker types"

    Mol Ther. ; 15(2):431-8 ; Feb 2007
    Fabry disease: the hematopoietic progenitors expressing alpha-galactosidase A restore lost enzymatic activity

    Fabry disease is a hereditary disease of the glycosphingolipids metabolism due to a deficit of the lysosomal enzyme, alpha-galactosidase A. A Canadian team tested the possibility of producing enzymes by bone marrow mononuclear cells infected by lentiviruses in Fabry model mice. They observed an increase in enzymatic activity associated with a reduction in glycolipids which accumulate in the cells of sick mice. In addition, the increase in this enzymatic activity may also be observed by infecting patients’ cells.
    Read the Pubmed abstract

    To read more about "Fabry disease"

    Gene Ther. ; 14(3):256-65 ; Feb 2007
    The expression of FRDA genomic locus corrects the phenotype of Friedreich’s ataxia patients’ cells

    Friedreich’s ataxia is due to a deficiency of the mitochondrial frataxin protein deficiency caused by an expansion of the intron I repetitions of theFRDA gene. The central nervous system and the heart are the main tissues affected. In order to re-establish the expression of the frataxin, Gomez-Sebastian et al. have infected patients’ cells with a vector permitting the expression of theFRDA genomic locus including the coding sequences, the endogen promotor, all the introns and the regulatory neighbouring sequences. By this approach, the researchers have both reestablished the expression of the frataxin and restored a normal cellular response to the oxidative stress.
    Read the Pubmed abstract

    To read more about "Friedreich ataxia"

    Mol Ther. ; 15(2):248-54 ; Feb 2007
    Large-scale hybridization of probes on genomic DNA represents a new tool for genetic diagnosis

    A major obstacle in the diagnosis of genetic diseases is the capacity to detect small chromosomal anomalies able to modify the number of locus copies anywhere in the genome. Patsalis et al. have perfected a new tool combining DNA microarrays and hybridization of specific amplifiable probes on genomic DNA. This technique has been tested using a blind test on DNA samples of ill or healthy men and women, with known or unknown X-chromosome anomalies. The deletions and duplications already indexed have been confirmed and new deletions have been identified then validated by FISH and PCR. These results demonstrate the power of this type of tool in genetic diagnosis.
    Read the Pubmed abstract

    Eur J Hum Genet. ; 15(2):162-72 ; Feb 2007

    Sotos Syndrome: pure duplication of the 15q26-qter region in a patient

    The Sotos Syndrome is a gigantism characterised by a macrocephalia and varying degrees of learning difficulties. Mutations in the NSD1 gene, encoding a histone-methyltransferase implicated in the regulation of transcription, are responsible for at least 75% of cases. Furthermore, patients with a duplication of the 15q26-qter region present similar phenotype characteristics, ie. A gigantism and a macrocephalia. Kant et al. have therefore researched the presence of this type of duplication in 38 patients affected by Sotos syndrome for whom no NDS1 mutation had been found. They thereby identified a duplication of the 15q26.1-qter region in one of these patients. The study of this region containing the candidate IGF1R gene therefore presents a particular interest for people affected by this syndrome without any NSD1 mutation.
    Read the Pubmed abstract

    To read more about "Sotos syndrome"

    European Journal of Human Genetics ; 50(1):1-10
    Wegener granulomatosis: intense agricultural activity is associated with a general development of the disease

    Wegener granulomatosis is a necrotizing vasculitis associating an inflammation of the vascular wall and a granulomatosis. The etiology of the disease is still unclear despite a possible role of genetic, microbial and environmental factors. Through the analysis of environmental exposure of patients diagnosed in the Norfolk region of the United Kingdom, Lee et al. were able for the first time to associate intense agricultural activities with the generalised development of the disease. Unfortunately, these results were not the subject of a statistical analysis due to the small number of patients included in the study.
    Read the Pubmed abstract

    To read more about "Wegener granulomatosis"

    Ann Rheum Dis. ; 66(2):278-9 ; Feb 2007
    A partial loss of STAR function associated with a mild form of congenital lipoid adrenal hyperplasia

    Baker et al. report on the case of 3 children with a non-classic form of congenital adrenal hyperplasia. Contrary to the classic form characterised by a severe adrenal incapacity experienced from early childhood and a total loss of androgenisation in 46, XY patients, they manifest the first signs of mild adrenal incapacity between the ages of two and four. In addition, the development of the male genitalia appears to be normal. The analysis of the sequence of the STAR gene, already involved in its classic form, has revealed two homozygotes mutations reducing protein activity by 80%.
    Read the Pubmed abstract

    To read more about "Adrenal hyperplasia, congenital"

    J Clin Endocrinol Metab ; 91(12):4781-5 ; Dec 2006
    New Clinical Trials registered by Orphanet
    An international multicentric clinical trial for treating patients who have undergone surgery for non-metastatic kidney cancer held in Germany, France, and Finland:

    Read about the trials in Germany
    Read about the trials in France

    Read about the trials in Finland

    New therapeutic & diagnostic approaches
    A high mortality rate following the replacement of the tricuspid valve in young children

    The tricuspid insufficiency is a frequent symptom in children with rare diseases such as Ebstein’s anomaly, pulmonary atresia or Fallot’s tetralogy. However, current studies dealing with the replacement of the tricuspid valve are essentially carried out in adults. A review analysing follow-up studies of 97 children who had had this surgery was carried out by Bartlett et al. This team thereby demonstrated that in young children, particularly those under the age of one year, the replacement of the tricuspid valve is associated with a high mortality rate. It therefore appears necessary to opt for other surgical acts in these young patients.
    Read the Pubmed abstract

    Circulation ; 115(3):319-25 ; 23 Jan 2007
    The third partial graft of the face has been performed in France

    The third partial graft of the face was carried out successfully on 21 January this year in a 29-year-old patient affected by neurofibromatosis type I. The operation, which was carried out by Prof. Lantiéri at Henri-Mondor Hospital in Créteil near Paris, consisted in the transplantation of the lower part of the face, according to a research protocol whose objective is to evaluate the feasibility of tissue allotransplantation in a series of five patients. The results will now depend on the success of immunosuppressor treatment which began three weeks ago.

    To read more about "Neurofibromatosis type 1"

    Down Syndrome: socio-economical inequalities confronted by prenatal diagnosis

    Using population-based data derived from 1433 cases of patients with Down syndrome in France between 1983 and 2002, a French team analysed the influence of the socio-economic situation on prenatal diagnosis access. The study shows that 70% of babies with Down syndrome are screened before birth. The rate of screening is variable according to lifestyle: 84% of working women and only 57% of unemployed women use screening facilities. The screening rate also varies according to ethnic origin: 73% of women of French origin use screening facilities compared with 55% of women of North African origin. Parallel to this, the weekly epidemiological bulletin of the French Health Ministry has just published a study on the social inequalities in French heathcare.
    Read the Pubmed abstract

    To read more about "Trisomy 21"

    Am J Public Health ; 96(12):2139-44 ; Dec 2006
    A new cellular diagnostic test is available in the USA

    Ikonisys Inc., an American company specialising in cellular diagnosis, has received FDA approval for marketing an automatic test enabling the identification and enumeration of chromosomes 13, 18, 21, X and Y in amniotic liquid cells. Based on the FISH method, this test will provide the laboratories with an economic solution when confronted with a lack of qualified technical staff.

    Genetic testing
    Monitoring Standards for Molecular Genetic Testing in the UK, Netherlands, and Ireland
    Read the UK Dept of Health Press Release

    Since molecular genetic technology has become part of many areas of clinical practice, it is fair to say that public expectations of this technology are understandably high. To ensure confidence in this technology continues, laboratories must implement high standards of quality assurance (QA) and external quality assessment (EQA), which is recognized as an essential component of QA. The United Kingdom National External Quality Assessment Service (UKNEQAS) for Molecular Genetics, which has been running since 1991, is currently the longest-serving provider of EQA to molecular genetic testing laboratories in the UK, Netherlands, and Ireland. Errors are rare, however, evidence from this and other EQA schemes indicate that a residual error rate does remain and it is believed this should be taken into account in clinical practice. This EQA scheme has evolved from the respective scientific bodies of the countries involved and continues to attach great importance to peer review practice. It is essential that steps taken to ensure quality in this rapidly expanding field be clear and transparent both to participants and the public. The authors describe the procedures developed and the governance imposed to monitor and improve analytical and reporting standards in participating laboratories and compare their experiences with those of equivalent EQA services in the USA.

    Simon C. Ramsden et al. Genetic Testing; Vol. 10, No. 3 : 147 -156; Sep 2006
    Read the full text
    US Genetics & Public Policy Center attacks the FDA for its “inequitable and inadequate” regulation of genetic tests

    In an online document entitled “FDA Regulation of Genetic Tests”, the US Genetics & Public Policy Center (GPPC) is scathing about what it calls the “inequitable and inadequate” current regulatory system operated by the FDA. The GPPC was set up in 2002 as an independent source of information on public genetic policy and technology. After outlining and explaining the status of test kits and ASR’s (Analytic Specific Reagents” used for home brew tests, in addition to Laboratory-developed genetic tests, in the USA, the Center comments on “Current Oversight Gaps and Consequences” with the FDA’s regulatory system. It claims that the FDA has not maintained “a consistent position” with regard to its laboratory-developed genetic test jurisdiction.

    Previously, the agency claimed it had authority to regulate these tests but was exercising enforcement discretion with regard to them. However, despite extending jurisdiction to one type of home brew test (IVDMIA), the FDA has not yet developed a clear position regarding the oversight of these home brew assays. For most genetic tests, claims the GPPC, “there is no government agency currently assessing whether genetic tests provide clinically relevant information to physicians and patients.” The Center concludes that the FDA’s current regulatory system is failing in its mission to protect the public’s health.

    Read the document: FDA Regulation of Genetic Tests


    Orphan Drugs
    New designations & authorisations in Europe
    European Marketing Autorisation for Inovelon®

    The anti-epileptic treatment, Inovelon® (rufinamide) from the Japanese company Eisai has received an AMM (Autorisation de Mise en Marché) for the EU for the additive treatment of the Lennox-Gastaut syndrome, a rare children’s neurological disease corresponding to a generalised epilepsy. The treatment, which is classified as an orphan drug for this indication, had already obtained a favourable opinion last November.
    Consult the list of Orphan Medicinal Products authorised in Europe

    To read more about "Lennox-Gastaut syndrome"

    European extension for an orphan drug in the treatment of renal cancer

    Sutent® (sunitinib) from Pfizer has just obtained a European extension for its indications in the first-intention treatment of advanced and/or metastatic renal cancer. The medicinal product available for oral use should be generally available in pharmacies this month. Sutent® which is classified as an orphan drug in the European Union, has already obtained an authorisation in the treatment of gastro-intestinal stromal tumours (GIST) since last summer, in patients who are resistant or intolerant to treatment using imatinib (Glivec®). In addition, this tyrosine kinase inhibitor is currently undergoing clinical development for renal cancer, this time as an additive, and is in phase III for breast cancer and colorectal cancer treatment.

    Tarceva® is given European approval for cancer of the pancreas

    The anti-cancer treatment, Tarceva® (erlotinib) from Roche, has just received European approval for the treatment of metastatic or non resectable cancer of the pancreas, in association with gemcitabine. Tarceva® is already indicated for non small-cell lung cancer in the USA and in Europe as well as for cancer of the pancreas in the USA. This new approval by the EMEA relies on the data of a pivot phase III study indicating that the association of Tarceva®/gemcitabine entails a significant prolongation of patients’ lives, compared with gemcitabine alone.

    Approval request for Thalidomide Pharmion® in untreated multiple myeloma

    Pharmion Corporation has submitted a request to the EMEA for an AMM regarding Thalidomide Pharmion® in the treatment of multiple myeloma. The submission is based on 4 phase III studies enroling 1400 patients the results of whom show an increased lifetime of 21 months when thalidomide is added to standard treatment. The treatment has been approved in Australia, New Zealand, Turkey, Israël, South Korea and Thailand, for the treatment of multiple myeloma following the failure of standard therapies. In geographical zones where this medicinal product is not authorised, such as the EU, it is currently dispensed on a nominative, compassionate basis and in France, using an Authorisation for Temporary Use (ATU).


    Ethical, Legal & Social Issues
    Bioethics law: 1st nationwide survey of opinion on bioethics issues in France is published

    An important step towards bioethics legislation in France, which could have a potential impact on corresponding bioethics regulation in Europe, was achieved this month when the results of the 1st public bioethics survey were announced at a Parliamentary debate held at the National Assembly in Paris. The French Biomedicine Agency (click into English version top right), the French authority of reference for bioethics, is calling for a major revision of the 2004 bioethics law due to make way for a new law in 2009. Since 6 August 2004, when the last such law was brought in, the French Biomedicine Agency is the only public body of its type in Europe to combine the 4 areas of organ procurement, procreation, human embryology and genetics. The Agency’s close relations with patients has given it a reputation for respecting safety and quality standards, as well as appropriate values with regard to ethics and transparency.

    The survey was based on a national sample of 1,086 people representing France’s adult population, and has enabled the Assemblée Nationale to draw up a major report on the new ethical questions raised concerning medically assisted reproduction (MAR), research on embryos and embryonic stem cells, and human genetics.

    The results of the survey reveal a surprising openness to certain aspects of scientific research formerly considered to be taboo or bordering on the unethical. According to the published results, 3 out of 4 French people believe that MAR techniques are preferable to adoption or giving up trying to have a baby when difficulties are encountered by a couple. Similarly, up to 46% of people questioned declared they were favourable to the idea that “a widow should be able to have a baby using the sperm of her deceased husband”. However, perhaps the most surprising results were that 95% of those questioned believe that prenatal diagnosis remains a “good thing” and that 80% believe that embryo research and human genetics represent “hope for the future and progress for patients and their families,” whilst only 19% think this is “going too far”.

    Of particular interest to the rare disease community: where a genetic disease is detected, according to those questioned, the couple should decide what should be done (89%). In this case, the relevant doctor’s advice is important for half of those questioned. The majority (3 out of 4) rejects the idea that the Law or an Ethics Committee should intervene in the decision-making procedure.

    Follow-up observations made by the French Biomedicine Agency following its survey include the remark that “these elements reveal an opinion the convictions of which are not stable, either by a lack of reflection or a lack of information or even because of the complexity of the subject, or even because it consists of intimate, personal subjects and a societal position does not yet make any sense”. The Agency concludes that “opinions on these subjects are still being formed”.

    Read the full results of the National Survey (in French only)

    Social issues
    Launch of the 1Million4Disability campaign: equal rights for European disabled citizens

    The European Disability Forum in Brussels is aiming to collect one million signatures across Europe in its call for more robust disability legislation. Situated within the context of the 2007 European Year of Equal Opportunities for All events, the campaign launch also coincides with the presentation of the new Eurobarometer for 2007. This indicates that 79% of Europeans believe that being disabled is a real disadvantage but more importantly, that 91% believe that the EU must make across-the-board efforts to eliminate the barriers still existing in the daily lives of disabled people living in Europe. The campaign seeks to mobilise European citizens to support the adoption of tougher, more far-reaching social legislation to ensure increased equal opportunities for Europe’s 50 million disabled people. A first symbolic signature was made in January at the campaign’s launch with some hundred representatives of the European disability movement, and civil society organisations, European institutions and the media. The collection of signatures will continue up until 4 October 2007 in Brussels in time for the official hand-over from Germany to the Portuguese Presidency of the EU.


    News from the Patients Associations
    Eurordis update
    A new Charter for patient-sponsor collaboration in RD clinical trials

    EURORDIS has launched a Charter targeting the improvement of cooperation between sponsors and patient organisations (POs) at the heart of the clinical trials process. This is an important issue for EURORDIS, whose 260 member POs from 30 countries will be directly concerned by the development of orphan drugs via clinical trials at the European level. The result of two years’ careful preparation based on in-depth consultations with its partners from the French Rare Disease Platform, such as the French Alliance for Rare Diseases, and its own Drug and Treatment Group, the draft document has passed through the hands of industrial and academic sponsors as well as regulatory agencies such as the EMEA* and public health stakeholders with unanimous approval. Initial results of these consultations were developed at the 3rd ERTC Workshop on RD Clinical Trials held in Barcelona in November 2005.

    The Charter’s aim is two-fold: firstly, it seeks to improve the quality of clinical research in RDs by cultivating transparent, trusting relations between sponsors and POs and secondly, to establish a set of general principles including the appropriate Confidentiality clauses and a template for a Agreement of Understanding (adaptable to any given RD). These guidelines are expected to improve this essential collaboration, which has often proved difficult to sustain over the lengthy period (sometimes years) which elapses between the initial identification of a potential molecule via the ensuing clinical trial process, right through to the drug’s final market availability. The idea is to maximise the patients’ own unique expertise concerning their disease and give them a more central role to play in this determining process, intervening “from A to Z”, rather than being sidelined for recruitment and medication update purposes.

    The Charter is already available in English and translation into several European languages is underway. The EURORDIS website will soon be posting up a patient information kit including a Charter user-manual, a glossary of terms, examples of agreements and a list of sponsors already signed up to the Charter.

    For more information, Contact EURORDIS

    * See the December edition of OrphaNews Europe on the EMEA’s “patient partnering”

    © freefoto


    Courses & Educational Initiatives
    EuroStemCell clinical workshop: towards clinical trials in muscular dystrophy

    Date: 3 April 2007
    Venue: Grand Hotel Villa Serbelloni, Bellagio, Italy

    This workshop will focus on recent developments in new experimental therapies for muscular dystrophy - from stem cells to gene therapy and new drugs. Speakers will make short presentations and position statements followed by in-depth general discussion. All participants are invited to make an active contribution.

    Registration is free of charge, and should be completed online via the website by 1st March 2007.

    More information

    A short course in ethics and law of genetics
    Date: 8 May 2007
    Venue: The Nowgen Centre, Manchester, UK

    This one and a half day course is aimed at clinicians and other professionals involved in the delivery of genetics services. Topics covered will include: Data Protection Act, Human Tissue Act, discrimination, duty of care and workplace testing.

    Read more about this Course


    Press & Publications
    New books
    The Autoimmune Diseases

    This book is written for clinicians implicated in the diagnosis and treatment of autoimmune diseases as well as for scientists wishing to follow developments in this field. The 4th edition of this medical classic is brought out nearly ten years after the last edition.

    Author : Noel R. Rose et Ian R. Mackay
    Publisher : Elsevier Academic Press
    1,134 pages, 199 $


    What's on where?
    In March
    Joint Meeting of the Belgisch-Nederlandse Neuromusculaire Studieclub and the German Reference Center for Neuromuscular Diseases
    Date: 23-24 March 2007
    Venue: Vaals, the Netherlands
    Contact for further information
    Read the First Announcement

    In April
    12th European Conference on Neurofibromatosis
    Date :26-29 April 2007
    Venue :Lisbon, Portugal
    More details

    In May
    Nuclear Receptor EMBO Conference
    Date:2-5 May 2007
    Venue:Gardone Riviera, Lake Garda, Italy
    More details

    9th European Symposium on the Prevention of Congenital Anomalies
    Date :7 May 2007
    Venue :Naples, Italy
    More details

    Newborn Screening and Genetic Testing Symposium
    Date :7-10 May 2007
    Venue :Hyatt Regency Hotel, Minneapolis, USA
    More details

    International MPS Network Conference
    Date :24-27 May 2007
    Venue : Serock, near Warsaw, Poland
    More details

    In June
    A Course on Sjogren Syndrome diagnosis and therapy for healthcare professionals and a Conference for patients with the syndrome
    Date: 22-23 June 2007
    Venue: Palacio de Congresos, Madrid, Spain
    Read the preliminary programmes (in Spanish only)
    More details (in Spanish only)

    In September
    Rare Diseases Research: Building on Success - a European Conference
    Date: 13 September 2007
    Venue: Charlemagne building- Brussels, Belgium
    Web details to follow shortly

    In October
    8th EPPOSI Partnering Workshop on Orphan Drugs
    Date: 18-19 October 2007
    Venue: Copenhagen
    More details coming shortly

    In November
    4th European Conference on Rare Diseases (ECRD 2007)
    Date :27-28 November 2007
    Venue :Lisbon, Portugal
    More details coming shortly


    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: Dr Ségolène Aymé
    Editor: Kathy Beuzard-Edwards
    Contact Us
    Editorial Board: Ségolène Aymé, Catherine Berens, Helen Dolk, Anders Fasth, Edmund Jessop, Jordi Llinares-Garcia, Annie Olry, Jérôme Parisse-Brassens, Claire Scharf-Kroener, Janos Sandor, Arrigo Schieppati, Rumen Stefanov, John F. Ryan, Domenica Taruscio
    For more information on the Rare Diseases Task Force
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