14 June 2007 print
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OECD issues quality assurance guidelines for genetic testing
The Organisation for Economic Cooperation and Development (OECD) has developed and published a set of quality assurance guidelines for international genetic testing. Observing that “research laboratories play a valuable role in the development and validation of new tests particularly in the provision of genetic testing for rare diseases”, the OECD asserts that the unique features of molecular genetic testing “place an enhanced duty on laboratories to assure the quality of their services…while governments, regulators and professional bodies have a responsibility to ensure that all genetic testing services are offered within a quality assurance framework that retains the confidence of the public.”

The Guidelines thus consist of “Principles and Best Practices for quality assurance in molecular genetic testing for clinical purposes” and are available to assist both OECD and non-OECD member countries in the development and introduction of appropriate quality assurance procedures. The OECD guidelines contain the following objectives:

  • Promoting minimum standards internationally for quality assurance systems and molecular genetic testing laboratory practices.

  • Facilitating mutual recognition of quality assurance frameworks.

  • Strengthening international co-operation and facilitating, where appropriate, the cross border flow of samples for clinical purposes in accordance with recognised principles for their handling, storage, safety, privacy and confidentiality.

  • Increasing public confidence in the governance of molecular genetic testing.

  • The Principles are designed for governments and those involved in the regulation of genetic services, while the Best Practices are primarily aimed at “professional associations, directors of molecular genetic testing laboratories and others involved in the provision of molecular genetic testing”. The OECD states “the ethical and legal principles set out in international declarations and agreements and the diversity of systems and jurisdictions within and between countries have been recognised during the development of these Guidelines.” The Guidelines address particular aspects of genetic services, particularly, “molecular genetic testing offered in a clinical context, and the quality assurance practices of laboratories that carry out such tests. They do not address testing carried out only for research purposes”. The publication of these guidelines will help contribute to providing equitable and uniform genetic testing practices for rare disease patients and their families across the world.

    Task Force Update
    On 30 May, an RDTF workshop, Assessing treatable rare diseases and the proportion of patients eligible for treatment took place in Paris at the Rare Diseases Platform located in Broussais Hospital. The workshop was attended by RDTF members and invited experts, patient organisation representatives, industry professionals, and Orphanet staff in an attempt to represent all stakeholders. The conclusions of this workshop will serve as a basis for the programme of the public workshop organised by EPPOSI taking place in Copenhagen on 18-19 October 2007 and will contribute to the elaboration of the Communication on rare diseases which is in preparation.

    We anticipate a productive Rare Disease Task Force meeting in Luxembourg on 20 June 2007 and look forward to seeing as many members as possible. The meeting is scheduled to take place between 10:00-17:30.

    We welcome the return of Louise Taylor as Editor for OrphaNews Europe and wish Kathy Beuzard-Edwards luck in her future endeavors.

    For more information about the Rare Diseases Task Force readers may consult the DG SANCO rare diseases website


    Spotlight on...
    Latin America and the Caribbean could play key role in search for rare disease solutions
    Virginia A. LLera, MD, is an Argentinian-born physician trained in psychiatry. Following the diagnosis of a rare disease in her daughter, Dr. LLera became aware of the many difficulties facing Latin American rare disease patients. She consequently founded the GEISER Foundation in 2001, a regional initiative designed to pool rare disease resources. Here, Dr. LLera describes for OrphaNews Europe the situation of rare disease patients in Latin America and the Caribbean as well as the initiatives underway to address their needs:

    Latin America is a subcontinent characterised by sharp social and economic contrasts. With few exceptions, the Latin American and Caribbean countries are small economies whose development has been slowed by poorly organized administrations and a lack of policies with long-term objectives. In this context, the fact that both the Pan American Health Organization (PAHO) and the World Health Organization (WHO) consider that the greatest inequities in health care provision, distribution and expenditure are found in Latin America and the Caribbean comes as no surprise.

    Living with a rare disease is a dramatic experience in Latin America and the Caribbean, since this region lags behind in economic and educational development, and inequalities in sanitary conditions permeate even the most basic social determinants of health, such as food, housing, education, or work. The lack of assistance available to rare disease patients involves deficiencies in economic and educational structures and impinges upon the natural rights of minority groups.

    Nevertheless, Latin America and the Caribbean may turn out to be key participants in the search for solutions for rare disease sufferers as far as access to diagnosis and treatment are concerned. Latin America and the Caribbean can make important contributions towards improved health care management for a number of reasons: the region has a large pool of patients, specialists, researchers and other human resources; it can help bring down global development costs and produce diagnostic and therapeutic tools affordable to the populations of developing countries; and it may expand the health care market considerably, thereby lowering investment risks for the industry.

    Rare diseases constitute the most inequitable area in health care, even in countries that have the most equitable health systems in the world. Thus, quite paradoxically, even though Latin America and the Caribbean show the greatest inequalities in health care, this region could become an important contributor towards balancing the issue on a global scale.

    At present there is no firm rare disease legislation in place, nor is there an organization comparable in magnitude or experience to the European framework. People living with rare diseases find themselves discriminated against by today's health care systems, a situation which encourages them to network with other patients who may suffer from completely different medical conditions but share similar social and sanitary problems. For this reason, several non-governmental organizations (NGOs) created by affected individuals and their families, specialized physicians or other vested interests, have set up support and advocacy groups, some of which form part of international associations. These groups, however, have little real chance to change the situation in Latin America and the Caribbean, because global health care patterns follow priorities that do not adequately reflect the particular concerns of this region. Hence, there is a need for an organization that can encompass all of these initiatives on a regional level and interact with counterpart organizations in the United States and in Europe on an equal footing.

    A first step toward union and organization was born in the Andean city of Mendoza, Argentina, where a group of health care professionals, patients and families affected by rare diseases created the GEISER Foundation (Group of Linkage, Research and Support for Rare Diseases), an umbrella organization designed to liaise with all of the rare disease associations in Latin America, identifying their shared needs and interests and fostering political, social and educational action to promote the common good. GEISER regards the problems pertaining to rare diseases and orphan drugs as matters of global interest and therefore seeks to bring together regional associations and organise them at the same level as their counterparts in the developed world, following the lead of the European Organization for Rare Diseases (EURORDIS) and the American National Organization for Rare Disorders (NORD). GEISER is building the power to draw resources and direct them towards achieving its goals, and considers its most valuable asset the unwavering determination of tens of associations scattered across Latin America that have already endorsed the Foundation's ideas. During the past five years, the GEISER Foundation has organised regional meetings with very positive response, and currently is working to arrange the first Latin American conference on rare diseases, scheduled to take place in Buenos Aires, on 27-29 March, 2008. It is expected that on such an occasion, a sub-continental organization capable of interacting with EURORDIS and NORD will be created to collaborate with these allies to change the history of inequalities in rare diseases in Latin America, the Caribbean and the rest of the world.

    Indeed, the issue of rare diseases and orphan drugs should be addressed rationally from a global perspective, in order to accelerate changes and maximise available resources. Since there are very few rare disease patients in each region, they cannot depend upon local policies or conditions; rather, they should be able to rely on international strategies designed to develop unified diagnostic and treatment methods, a single, profitable channel of health products distribution and an organised network to facilitate access to health care resources. The coordinated participation of all Latin American countries is essential to cooperate with multicenter studies and research centers working on diagnostic and treatment techniques, and to promote initiatives for regional development and harmonised sanitary, legal and educational policies. At the same time, such participation will considerably expand the market for health care products, thus helping improve investment returns and reduce costs.
    One of the aims will be to make access to diagnosis and treatment more readily available within the region. In order to achieve this goal, it will be necessary to reach international consensus on regulations and funding. Should some of these changes be implemented in the region, they will also have an impact on the rest of the world. Measures taken to address regulatory and intellectual property issues in the field of rare diseases could also be adapted to rectify inequities in neglected diseases, which are one of the most pressing problems in Latin America and the Caribbean.
    This could be the first opportunity for Latin America and the Caribbean to begin serious work on harmonised, comprehensive policies; surely the experience and benefits derived from such work will have a positive influence on other social and sanitary structures in the region.
    Contact Virginia LLera


    EU Policy News
    EESC calls for enhanced access to equal opportunity for the disabled
    The European Economic and Social Committee (EESC) recently published an Opinion in the Official Journal of the European Union concerning equal opportunities for people with disabilities. In this paper, the EESC invites the European Commission to submit a proposal for comprehensive legislation addressing the needs and challenges of disability. The many areas targeted for legislation include housing, with a call for an examination of alternatives to existing institutions that often segregate and marginalise people with disabilities; the employment sector, extending protection from work discrimination and more opportunity; and a global improvement of access, including such diverse areas as public buildings, transport, information technologies, support for families, and especially education for children. The opinion calls for an extension of existing European-level legislation and reinforces the principle of inclusion of disabled people in decision-making, with a renewed call for governments to better support the networks of disability organizations. While acknowledging the diversity existing between different disabilities, the authors stress the need for a common European definition of disability, in order to make EU-level policies more effective. Thus, the Commission, Member States, and Eurostat are all entreated to devote more resources to an "elaboration of statistics" analysing employment, economic issues, consumption, and access to services.
    EuroGentest solicits feedback for its genetic counseling recommendations
    EuroGentest, the European Network of Excellence for genetic testing, is busy developing a set of Recommendations destined for those whose role involves counseling genetic testing patients. EuroGentest is thus requesting feedback on its second draft of these guidelines. All concerned parties are strongly encouraged to take the time to read the Recommendations and offer comments.

    National & International Policy Developments
    Switzerland adopts orphan medicine legislation similar to EU regulations
    Switzerland has adopted legislation for its orphan medicinal products comparable to regulations already in effect in the European Union. Parallel to the European Medicines Agency (EMEA), the designation “orphan” in Switzerland is applicable to illnesses afflicting five or less persons per 10,000. Scientific advice is offered before a demand for authorisation is made, and manufacturers may be exempt from certain administrative taxes. Under the Swiss federal law of 15 December 2000 concerning therapeutic products for human or veterinary purposes, medicinal products destined for rare diseases benefit from simplified authorisation procedures. Under the new legislation, in effect since the end of 2006, Swiss national medicinal agency Swissmedic Institute distinguishes between the processes of granting orphan status for a medicinal product and granting marketing authorisation for a product with an orphan designation.

    The status orphan medicines receive is largely equivalent to that bestowed on rare disease products by the EMEA, granted to products aiming to diagnose, prevent or treat diseases that endanger the life of a patient or cause chronic disability, and that affect no more than 5 in 10,000 persons in Switzerland at the time of the demand for authorization. To determine orphan status, Swissmedic uses statistics, scientific literature, and relevant databases concerning the rarity of an illness along with the specific details of the illness. A medicine already designated as “orphan” in another country (employing similar testing and safety standards as Switzerland) can thus obtain orphan medicine status in Switzerland for the same indication if the applicant can demonstrate that the product is identical. The granting of orphan status can thus be bestowed without re-evaluation of the rarity and gravity of the illness. Orphan status can be removed if the conditions are not fulfilled.

    The procedure for demanding authorisation for an orphan medicinal product is similar to that of non-orphan products, but with some differences: scientific advice is offered before submitting a demand for authorization, and pharmaceutical companies may be exempt from administrative and/or sales taxes. As mentioned, if the medical product has been granted authorisation in a country employing quality control and safety norms equivalent to Switzerland, “the applicant may furnish the documentation on the quality, toxicology and clinical results that permitted authorization” in that country. To date, 14 products have obtained orphan status, of which five have received authorization to be placed on the market.

    France approves 29 additional rare disease centres of reference
    As part of its 2005-2008 National Plan for Rare Diseases, France has designated an additional 29 centres of reference for rare diseases in 2007, bringing the current total number of centres to 132. These new centres, valid for a five-year period, concern 11 different groups of rare diseases. The next step will be the creation of centres of competence, which, working with the centres of reference, will provide treatment and follow-up for patients closer to their homes. For more information, read the legislation accompanying the creation of centres of reference in France and the circular concerning the creation of centres of competence.

    Orphanet News
    New Texts
    New Orphanet Journal of Rare Diseases publications
    Intrahepatic cholestasis of pregnancy
    Ellis-Van Creveld syndrome
    Fibromuscular dysplasia
    Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene

    and in the European Journal of Human Genetics (in association with Orphanet):
    Marfan syndrome: clinical diagnosis and management

    New Research Projects open for Recruitment
    Study to evaluate the visual faculty with a retinal implant system

    A double-blind, randomised, placebo-controlled study of the efficacy, safety and tolerability of idebenone in the treatment of patients with Leber's Hereditary Optic Neuropathy (LHON)


    New Syndromes
    Angioma serpiginosum with oesophageal papillomatosis is an X-linked dominant condition that maps to Xp11.3-Xq12
    Angioma serpiginosum is a congenital skin disease characterized by a progressive dilatation of the sub-epidermal vessels. These vascular streaks are present at birth and progress slowly thereafter. To date, only dominant autosomic transmission has been described. The authors describe a family in which only the females are affected, suggesting a dominant X-linked transmission linked with in utero death of afflicted males. The analysis of cells from 11 patients linked the Xp11.3-Xq12 region to the disease. Papillomatosis of the entire oesophagus and mild nail and hair dystrophy was found in some family members, indicating that this condition could be a mild variant of Goltz-Gorling syndrome.

    Read the Pubmed article

    Eur J Hum Gen ; 543-547 ; May 2007
    Persistent placoid maculopathy: a new clinical entity
    The authors describe a previously unreported clinical entity superficially resembling macular serpiginous choroiditis yet with a distinct presentation and clinical course. Using a retrospective review of the medical records of five patients, aged 50 to 68 years, persistent placoid maculopathy has features resembling macular serpiginous choroiditis but differs in its clinical course and effect on visual acuity and thus appears to be a new entity. In contrast to serpiginous choroiditis, visual acuity remained good despite early involvement of the fovea until complications related to choroidal neovascularization (CNV) or pigmentary mottling developed. Unlike serpiginous choroiditis, the white macular lesions faded over a period of months to years, but the characteristic angiographic findings often persisted longer. CNV developed in nine of 10 eyes with subsequent conversion to disciform macular scars in seven of 10 eyes. Unlike serpiginous choroiditis, none of the eyes showed chorioretinal scar formation unless related to CNV.

    Read the Pubmed article

    Trans Am Ophthalmol Soc. ; 108-120 ; December 2006

    New Genes
    RAB23 Mutations in Carpenter Syndrome Imply an Unexpected Role for Hedgehog Signaling in Cranial-Suture Development
    Carpenter syndrome is a very rare subtype of acrocephalopolysyndactyly (ACPS) disorders. It is determined by acrocephaly, peculiar facies, cardiac defects, obesity, and malformations in the hands and feet. Using homozygosity mapping, the authors identified five different mutations of RAB23 in 15 families. RAB23 encodes an enzyme of the GTPase family of vesicle transport proteins and acts as a negative regulator of hedgehog HH signaling. Unexpectedly, the discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranial-suture biogenesis, and provides a new molecular target for studies of obesity.

    Read the Pubmed article

    The American Journal of Human Genetics ; 1162-1170 ; June 2007
    Matthew-Wood Syndrome Is Caused by Truncating Mutations in the Retinol-Binding Protein Receptor Gene STRA6
    Matthew-Wood syndrome is an extremely rare disease with main characteristics including anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Mutations were discovered in STRA6 in two human fetuses from consanguineous families. STRA6 encodes an integral cell-membrane protein involved in the absorption of retinoic acid, a molecule involved in numerous developmental anomalies. No mutation in the gene was identified in five other fetuses presenting at least one of the two principal clinical signs of the illness.

    Read the Pubmed article

    The American Journal of Human Genetics ; 1179-1187 ; June 2007
    Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility
    Male infertility is considered responsible for 20%-50% of the estimated 80 million infertility cases worldwide. The authors studied ten infertile men all presenting normal somatic karyotype but spermatozoa characterized by large heads, a variable number of tails and an increased chromosomal content. Using a genome-wide microsatellite scan, the authors identified a common region of homozygosity harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in the AURKC coding sequence. In addition, they showed that this founder mutation resulted in premature termination of translation, yielding a truncated protein that lacks the kinase domain.

    Read the Pubmed article

    Nat Genet ; 661-665 ; May 2007
    A new CDG syndrome sub-type caused by COG8 deficiency
    CDG syndrome consists of a group of autosomic recessive diseases affecting the synthesis of glycoproteins and characterized by neurological and/or multivisceral disorders. Certain forms of the disease have been linked to a deficit in a COG subunit, which is essential for the structure and function of the Golgi apparatus through regulation of membrane trafficking. Two teams have identified COG8 homozygote mutations in two patients. In both cases, COG8 mutations severely truncated the protein and destabilized the COG complex. The authors propose calling this new disorder CDG-IIh or CDG-II/COG8.

    Read the abstract of the first PubMed article
    Read the abstract of the second PubMed article

    Hum Mol Genet ; 717-730 ; 1 April 2007
    Hum Mol Genet ; 731-741 ; 1 April 2007

    Gene linked to Fanconi anemia complementation group I identified
    Fanconi anemia (FA) is a developmental and cancer-predisposition syndrome including bone-marrow failure, a variety of congenital malformations, a propensity to develop acute myeloid leukemia (AML) and cellular hypersensitivity to DNA cross-linking agents. It is caused by mutations in genes controlling DNA interstrand crosslink repair. The authors describe the FA protein FANCI, identified as an ATM/ATR kinase substrate required for resistance to mitomycin C. FANCI shares sequence similarity with FANCD2, likely evolving from a common ancestral gene. Mutation in FANCI is responsible for loss of a functional FA pathway in a patient with Fanconi anemia complementation group I.

    Read the Pubmed article

    Cell ; 289-301 ; 20 April 2007
    A mutation in FGFR1 linked to isolated hypogonadotropic hypogonadism
    Hypogonadotropic hypogonadism, resulting from an insufficient secretion of gonadotrophin hormones, can present in an isolated form or as a syndrome, as is the case with Kallman syndrome, characterised by hypogonadotropic hypogonadism and anosmia (lack of sense of smell) and that can be due to FGFR1 mutations. The authors have now identified mutations in gene FGFR1 in four patients with an isolated form of the disease (without anosmia). These mutations have not been observed elsewhere to date.

    Read the Pubmed article

    J Clin Endocrinol Metab ; 1155-1158 ; March 2007

    Research in Action
    Fundamental Research
    Astrocytes are responsible for motor neuron death in amyotrophic lateral sclerosis
    Amyotrophic lateral sclerosis is a degenerative nervous system disorder caused by a progressive loss of motor neurons. Ten percent of observed cases are hereditary and some 25% of these are caused by dominant mutations in superoxide-dismutase -1 (SOD1). Two different American research teams describe the mechanism causing the progressive loss of neurons, showing that mutated SOD1 has a toxic effect when expressed in the astrocytes rather than in the motor neurons themselves. The expression of mutated SOD1 in the astrocytes leads to the release of soluble toxic factors responsible for the death of adjacent motor neurons. Identification of these factors yields new pathogenic and therapeutic possibilities.

    Read the abstract of the first PubMed article
    Read the abstract of the second PubMed article

    Nat Neurosci ; 615-622 ; May 2007
    Nat Neurosci ; 608-614 ; May 2007

    OGG1 initiates age-dependent CAG expansion in somatic cells
    Huntington disease is a neuro-degenerative illness caused by the expansion of CAG repetitions in the Huntingtin gene. This expansion is present in all cells of the organism but may increase in certain brain cells during the patient’s lifespan. The authors demonstrate, using a transgenic mouse model, that age-dependent expansions occur during the process of removing oxidized base lesions and is dependant on base excision repair enzyme OGG1. This reparation mechanism is identified for the first time as responsible for the expansion of repetitions observed in the brain of patients.

    Read the Pubmed article

    Nature ; 447-452 ; 24 May 2007
    An imbalance between the number of neurons and astrocytes contributes to cognitive deficit in Noonan Syndrome
    Noonan syndrome is characterized by small stature, facial dysmorphism and congenital heart anomalies. Light mental disability may also be observed. Fifty percent of cases are caused by mutations in PTPN11, coding an abnormally active tyrosine phosphatase. Study of this enzyme, in cell cultures and animal models, demonstrates that constitutive activation affects neurogenesis and the differentiation of astrocytes. An imbalance between an abnormally large number of neurons and small number of astrocytes thus may contribute to cognitive impairment in Noonan syndrome patients.

    Read the Pubmed article

    Neuron ; 245-262 ; 19 April 2007
    NOTCH3 CADASIL-associated mutations appear to create novel pathogenic roles
    Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukocephalopathy (CADASIL) is a disorder characterized by multiple infarctus and vascular dementia. Pathogenic mutations in the disease gene NOTCH3 provoke the accumulation of the protein in the extracellular domain of the arterial smooth muscle cells. The authors succeeded in restoring a normal phenotype in a mouse by expression of a mutated form of the NOTCH3 gene described in CADASIL (mutation R90C). The authors thus demonstrate that the mutant protein is functional and does not interfere with the normal activity of the protein. These facts suggest that in CADASIL arteriopathy, the mutated NOTCH3 protein invokes a novel role rather than interference with the physiological function of the protein.

    Read the Pubmed article

    Hum Mol Genet ; 982-992 ; 15 April 2007
    The Shwachman-Diamond syndrome protein is essential to the maturation of ribosomes
    Shwachman-Diamond syndrome, is marked by the association of an haematological defect with a dysmorphic syndrome characterised by lipomatosis of the pancreas resulting in external pancreatic insufficiency. Other clinical signs include cutaneous effects (ichtyosis), bone defects (metaphyseal dysostosis, pectus carinatum), and psychomotor retardation. The authors studied the role of yeast SBDS ortholog Sdo1 and demonstrate a role of this protein in 60S ribosomal subunit maturation and therefore the translation in proteins of messenger RNAs.

    Read the Pubmed article

    Nat Genet ; 486-495 ; April 2007
    Clinical Research
    Secondary mutations in LAMB3 restore phenotype in patients with junctional epidermolysis bullosa
    Junctional epidermolysis bullosa causes the formation of blisters between the dermis and the epidermis, leading to infected scabs and lesions. Mutations in LAMB3 encoding laminin-332 could be at the origin of the development of the disease. Dutch scientists describe two patients presenting spontaneous localised healing in different parts of the body attributed to secondary mutations that affect different laminin-332 amino acids and re-establish a normal expression. The discovery of this phenomenon opens new therapeutic possibilities: patients presenting with these reversals may benefit from transplants using their own cells carrying revertant mutations.

    Read the Pubmed article

    J Clin Invest ; 1240-1248 ; May 2007
    New susceptibility loci for Crohn disease
    Crohn disease is a chronic intestinal inflammatory infection manifesting in diarrhea, abdominal pain and weight loss associated with fever, aphtosis, arthralgia, and erythema nodosa. Its cause remains unknown but genetic susceptibility has been described. Two separate studies have identified five new susceptibility loci for the disease. Both studies employ particularly large cohorts: 547 patients in one and 988 in the other.

    Read the first Pubmed abstract
    Read the second Pubmed abstract

    PLoS Genet ; 20 April 2007
    Nat Genet ; 596-604 ; May 2007
    New clinical data for children afflicted with Brugada syndrome
    Brugada syndrome is an arrhythmogenic disease characterised by an augmented risk of sudden cardiac arrest. Little is known of this disease in children. The authors describe 30 children under 16 years of age from 13 different European hospitals. Analysis of the data revealed fever to be the principal precipitating factor for an arrhythmic event. As with the adult population, the risk for arrhythmic events was higher in previously symptomatic patients and those displaying a spontaneous type 1 ECG.

    Read the Pubmed abstract

    Circulation ; 2042-2048 ; 17 April 2007
    Recommendations for conducting systemic vasculitis clinical studies and/or trials
    An expert consensus group of rheumatologists, nephrologists and internal medicine specialists from five European countries and the US analysed the literature in order to establish the European League Against Rheumatism (EULAR) recommendations for conducting systemic vasculitis clinical studies and/or trials. The group concluded that sufficient evidence existed only for anti-neutrophil cytoplasm antibody-associated vasculitis and thus the recommendations focus on these diseases.

    Read the Pubmed abstract

    Ann Rheum Dis ; 605-617 ; May 2007
    Gene Therapy
    Chaperone proteins reduce proteic aggregates in Huntington disease rat models
    Huntington disease is an inherited neurodegenerative disorder caused by an expansion of glutamine repeats in the huntingtin protein. The mutated protein thus refolds abnormally, forming aggregates in the cells. French researchers have studied the effects of two chaperone proteins, hsp104 and hsp27, for their capacity to re-establish normal refolding of proteins in cells expressing a mutated huntingtin and in rat models of the disease. In both cases, a protective effect of the chaperones on the mutated protein was observed, as well as an improvement of neuron functioning in the striatum - the region of the brain affected by the disease.

    Read the Pubmed abstract

    Mol Ther. ; 903-900 ; May 2007
    Therapeutic Approaches
    PTC124 allows for the production of functional proteins despite the presence of nonsense mutations
    Numerous genetic diseases are caused by mutations introducing a STOP codon in a gene, provoking a premature translational termination. This can lead to a major reduction in the expression of the mutated protein or a normal quantity of a truncated non-functional protein. A recent therapeutic approach consists of employing molecules capable of acting directly on the translation of the RNA messengers and suppressing certain STOP codons. The authors have identified and tested such a new chemical compound: PTC124. This molecule has been tested on human muscular cells with mutated dystrophin and in mice models with Duchenne muscular dystrophy (mdx mouse). PTC124 increases normal dystrophin production and improves muscular function in mice. PTC124 is currently used orally in Phase II clinical trials for the treatment of cystic fibrosis and Duchenne muscular dystrophy in patients with a nonsense mutation. Both the EMEA and the FDA have granted orphan medicinal product status to the compound for these two indications.
    Read the PubMed abstract

    Nature ; 42-43 ; 3 May 2007
    Cyclin-dependent kinase inhibition is beneficial in mice with systemic lupus
    Systemic lupus erythematosus (SLE) is a heterogeneous auto-immune disease characterised by the presence of anti-nuclear auto-antibodies. The most severe manifestations include kidney inflammation, neurological problems, anemia and reduced platelet count. The authors tested the effect of seliciclib, a cyclin-dependent kinase inhibitor, on SLE-afflicted mouse models. When administered at an early phase of the disease, seliciclib prolonged survival, delayed renal function impairment and protected the kidneys from inflammation and lesions, thus suggesting a new approach to SLE treatment.
    Read the PubMed abstract

    Arthritis Rheum ; 1629-1637 ; May 2007

    Patient Management and Therapy
    Butyrate reduces GPI deficiency and treats epilepsy in one patient
    Inherited deficiency of glycosyl phosphatidyl inositol (GPI) causes splanchnic vein thrombosis and epilepsy. It is due to homozygous mutations in the promoter region of PIGM gene encoding mannosyl transferase. The authors demonstrate that this results in histone hypoacetylation at the promoter of PIGM. The histone deacetylase inhibitor butyrate increases PIGM transcription and surface GPI expression in vitro as well as in vivo. More important, the drug caused complete cessation of intractable seizures in a child with inherited GPI deficiency.

    Read the Pubmed abstract

    New Eng J Med ; 1641-1647 ; 19 April 2007

    Orphan Drugs
    Two companies collaborate to develop rare disease medicines
    AVI BioPharma and Ercole Biotech have announced a cross-licensing and collaboration agreement to develop medicines that may prove effective in treating genetic diseases Duchenne muscular dystrophy (DMD) and beta thalassemia. Under the terms of the agreement, AVI and Ercole will work together in the development of products, with AVI leading the DMD program and Ercole leading the thalassemia program. Each company has the option of co-funding the program led by the other party and sharing equally in the financial returns from resulting products. The technologies developed by Ercole and AVI allow manipulation of the RNA splicing process and the production by cells of clinically desirable variants of relevant proteins.

    News from the Patients' Associations
    Patient groups in attendance at Romanian medical conference
    Both the Romanian Prader Willi Association and the Williams Association were present at the annual Conference of the Romanian Medical Society that took place in Moeciu de sus-Brasov, Romania in late May, reminding attendees of the resources provided by their Information Center for Rare Genetic Diseases. The first of its type in Romania, this center is a resource for patients with rare diseases, their families, and specialists involved in the diagnosis and management of these diseases. The two associations seek to position the Romanian National Alliance for Rare Diseases (RONARD), supported by a grant from the Trust for Civil Society in Central and Eastern Europe, as an important project.

    What's on Where?
    European Human Genetics Conference 2007
    Date: 16-19 June 2007
    Venue: Nice, France
    More details

    1-day Conference: Clinical Research for Rare Diseases: Opportunities, Challenges and Solutions
    Date: 5 September 2007
    Venue: Washington, DC, USA
    More details

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

    4th Stem Cell Gene Therapy Conference
    Date: 13 September 2007
    Venue: Halkidiki, Thessaloniki, Greece
    More details

    EuroGentest Workshop on internal auditing for genetic testing laboratories
    Date: 20-21 September 2007
    Venue: Leuven, Belgium

    Registration is open for this event, which is EuroGentest's next workshop. The topic of the upcoming workshop will be internal audit for genetic testing laboratories. The content will be similar to that of the previous workshop on internal audit, the content will be mainly the same. EuroGentest will have general presentations, role play, video fragments and group discussions on how to prepare, execute and report internal audits. Registration deadline: 15 July 2007

    More details and to register now

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

    3rd International Meeting on Congenital Disorders of Glycosylation
    Date: 18-19 October 2007
    Venue: Paris
    This international meeting on CDG is preceeded by the 3rd Orphan Focus Course on "Protein Glycosylation in Health and Disease" on Oct 16-17. For more details on the course
    More details on the conference

    Biology and clinical applications of cord blood cells
    Date: 19-21 October 2007
    Venue: Paris, France
    More details

    4th European Conference on Rare Diseases (ECRD 2007)
    Date: 27-28 November 2007
    Venue: Lisbon, Portugal
    NB: Registration is open. Deadline for abstract submission: 30 May 2007
    More details

    15th Annual Meeting, Int'l ALS/MND Associations Alliance & 18th ALS/MND Int'l Symposium
    Date: 1-3 December 2007
    Venue: Toronto, Canada
    More details


    Press & Publications
    Neurology of hereditary metabolic diseases of children : 3rd Edition
    Authors: Gilles Lyon, Edwin H. Kolodny, Gregory M. Pastores
    Editor: McGraw-Hill
    This third edition is destined for pediatric neurologists, interns, and medical students as well as all those interested in hereditary metabolic diseases.


    Orphanews Europe, the newsletter of the Rare Diseases Task Force
    Orphanews Europe is supported by the European Commission's DG SANCO
    and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Ségolène Aymé
    Editor: Louise Taylor
    Contact Us
    Editorial Board: Ségolène Aymé, Catherine Berens, Kathy Beuzard-Edwards, Helen Dolk, Anders Fasth, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Claire Scharf-Kroener, Janos Sandor, Arrigo Schieppati, Rumen Stefanov, Domenica Taruscio, Joan Luis Vives Corrons
    For more information on the Rare Diseases Task Force
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