16 September 2009 print
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In its first month heading the EU, Sweden gathers experts to harmonise procedures for assessing marketed orphan drugs

On 1 July, Sweden took over the Presidency of the European Union (EU), completing the 18-month troika started under France and continued via the Czech Republic. The country holding the EU Presidency acts as the driving force behind the EU’s legislative and political activities and works to broker compromises between the EU Member States. The most important task for the three-Presidency team is to establish a common 18-month programme for all three presidencies. Following on the momentum initiated by France and sustained by the Czech Republic, during which the historical adoption of the Council Recommendation on an Action in the Field of Rare Diseases was achieved in June of this year, Sweden, less than one month into its turn at the helm of the EU Council Presidency, organised a conference of experts to push the envelope further. On 28-29 July, Assessing Drug Effectiveness – Common Opportunities and Challenges for Europe gathered stakeholders from throughout Europe to discuss how to develop cooperation across Europe for the collection and sharing of data on drug effectiveness and safety following marketing authorisation. Speakers included Thomas Lönngren, Executive Director of the EMEA, along with representatives from government, industry, research, and patient organisations. A workshop specific to orphan drugs – an area for which cooperation is considered critical as most individual countries have too few patients and resources to sustain a comprehensive follow-up scheme – brought together a panel of experts including Ségolène Aymé (Orphanet, RDTF Task Force), Yann LeCam (EURORDIS), Kerstin Westermark (Committee for Orphan Medicinal Products), Andrea Rappagliosi (EFPIA Economic & Social Policy Committee), Ad R. Schuurman (Dutch Health Care Insurance Board, MEDEV), Josep Torrent-Farnell (Autonomous University of Barcelona), Stanislav Primožič (Agency for Medicinal Products and Medical Devices of the Republic of Slovenia) and Giulia Del Brenna (DG Enterprise). The conference moved forward the process of post-marketing assessment harmonisation via the decision to develop a pilot model “for structured follow-up for initial testing on an orphan drug” for which several candidate products were proposed by the workshop panellists. A meeting to take place in autumn will bring together stakeholders interested in participating in the pilot project. An informational booklet is available describing the issues surrounding sharing common assessment data in Europe. Consult the conference press release, agenda and speaker presentations

EU Policy News

EMEA 2008 annual report reveals sustained activity for orphan drugs
The European Medicines Agency Annual Report for 2008 describes the year as one of “consolidation and steady progress” while qualifying the assessment processes for medicines, including orphan medicinal products, as “intensive”. In 2008 the EMEA received 119 orphan designation applications, of which 86 positive opinions were issued by the Committee for Orphan Medicine Products (COMP). Of these, oncology products once again took the lion’s share. In 2008, almost two-thirds of orphan designations concerned products for paediatric populations. In terms of marketing authorisation, there were 13 orphan drug applications amongst the total 103 requests, up slightly from 2007 but down from 2006. Of the 66 new products receiving marketing authorisation in 2008, the EMEA report singles out a dozen – half of which are for rare disorders – as being especially noteworthy in terms of public-health interest. The report also documents the ongoing protocol assistance for orphan medicinal product development, continued support for small and medium-sized enterprises (SMEs), and the establishment of the EMEA’s sixth scientific committee — the Committee for Advanced Therapies (CAT) — which is expected to be highly relevant to rare disease treatment development. Finally, the report outlines the considerable activities undertaken to strengthen and expand European and international cooperation and to further engage consumers, patients, and health professionals. The actions to improve communication and transparency are also detailed.
Access the full report or a summary

A European and USA joint effort to promote good clinical practices is expected to benefit orphan drug trials
As part of the ongoing confidentiality agreement between the European Commission, the European Medicines Agency, and the US Food and Drug Administration, a new initiative launched an 18 month pilot phase on 1 September. The Good Clinical Practice Initiative - a reflection of both the increasing globalisation of clinical studies and limited inspection resources - defines its objectives as “the sharing of information on inspection planning, policy and outcomes and the conduct of collaborative inspections”. The small patient populations typically available for rare disease medicinal product trials dispose such trials to international participation. By harmonising inspection procedures, the new initiative is expected to play a key role in ensuring that trials are conducted under safe, ethical, and uniform conditions. One of the principle objectives for the pilot phase of the initiative includes the exchange of Good Clinical Practice-related information “contained in applications for scientific advice, orphan medicines designation, paediatric investigational plans, marketing authorization or post-authorization activities of significant public health interest”. In a press release, the FDA and EMEA announced that they “are looking to partner with applicants/sponsors who are willing to volunteer during the pilot phase of the initiative to engage in dialogue and planning of joint inspections involving applications that are anticipated to be submitted fairly simultaneously to both regulatory agencies within the next 12 months”.
For further information


National & International Policy Developments
Six Central European countries form alliance to share rare disease resources

In a follow-up gathering to the August 2008 Informal Meeting of Regional Health Ministers, during which rare disease issues figured on the agenda, participants from six Central European countries met last month to discuss how to better cooperate and coordinate efforts for rare disease patients. Both representatives of government and rare disease experts contributed to informal meetings that took place at the initiative of the Austrian Ministry of Health and the European Health Forum Gastein. The recent adoption by the European Parliament of the Cross-Border directive (see OrphaNews Europe 20 May 2009) facilitates the sharing of health care resources between EU countries. In a press release, several key elements of the Central European initiative were outlined:

  • Participating countries agree to cross-border cooperation in research and care in the area of rare diseases
  • Participating countries will develop a coordinated profile of requirements stipulating the criteria that must be adhered to by future centres of expertise
  • In each of the participating countries, centres of expertise for certain diseases or disease groups will be identified and established. Existing specialised hospitals and institutes will be implicated in order to utilise their knowledge as efficiently as possible
  • Networking the centres of expertise is meant specifically to facilitate a more intense transfer of know-how; patients are to be provided with simple and rapid options for taking advantage of the services in centres of expertise abroad, and the development of a patient database is to create a better basis for studies and research projects
  • For each participating country, a coordination office will be established accessible to both physicians and patients

  • Till Voigtländer, a specialist in neurobiology at the Institute of Neurology of the Vienna Medical School and country coordinator for Orphanet Austria, qualified the new alliance as an “important step forward in the development of common strategies for rare diseases for small and medium sized countries” commenting that the “concept of officially labelled (European) centres of expertise, certified on a national or … regional level, is now accepted and favoured by a cluster of neighbouring countries (not just single, scattered ones) and will receive a high priority on the political agenda in each participating member state”. Dr. Voigtlander remarked that such a development, “acknowledges the pivotal role centres of expertise could play in the development of better-structured health care pathways and the overall improvement of health care quality for patients affected with rare diseases”.

    In a press release, European Health Forum Gastein President Günther Leiner observed that “in hardly any other area does an international network promise such enormous improvements as with rare diseases”. Robert Schlögel, Director General in the Austrian Ministry of Health, concurred that “rare diseases always affect only a few people, yet they, too, are entitled to the best possible treatment for their afflictions, and with close international cooperation we can decisively improve the conditions for this.”

    The six participating countries are Austria, Czech Republic, Germany, Hungary, Italy, and Slovenia, and cooperation is open for additional partners. As Ministry of Health Director General Schlögel pointed out, “Smaller countries have especially big advantages resulting from cooperation in the area of cross-border diseases, thus in this regard we intend to play a vanguard role. Our goal is for our initiative to be seized by as many European countries as possible and for that reason cooperation for every country is open.”

    Results from the meeting of experts are to be presented to the health authorities of the participating countries. The initiative aims to open the first centre of expertise in 2010. Contact the International Forum Gastein

    FDA modifies regulations to expand access to investigational drugs
    In the USA, the Food and Drug Administration (FDA) has clarified and adjusted its regulations governing investigational medicinal products to expand access for both individuals and groups of patients. Often referred to as “Compassionate Use”, the administration of medicinal products that have not yet received approval from a country’s drug regulatory agency is typically for “patients with serious or immediately life-threatening diseases or conditions when there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the patient’s disease or condition”. The practice of compassionate use is highly relevant to rare disease patients. The new FDA rules expand access for individual patients, including in emergency situations; intermediate-size patient populations (smaller than those typical of a treatment investigational new drug application (IND) or protocol); and treatment INDs or treatment protocols. Amongst the modifications, access is granted to patients with a serious disorder (as defined under the new regulations), whether or not the patient is actually seriously ill at the time of the request. The rules also clarify the circumstances under which charging monies for an investigational drug is permitted and specifies the costs that can be recovered. The FDA has launched a new website that provides information on investigational drug options for both patients and healthcare professionals.
    Consult the FDA regulation Expanded Access to Investigational Drugs for Treatment Use
    Consult the new FDA website for investigational drug options

    Other European news
    Germany and Poland’s First Ladies team up to bring awareness for rare diseases to the general public

    In July of this year the First Lady of Poland, Mrs Maria Kaczynska, and her German counterpart, Mrs Eva Luise Köhler, visited the Children’s Memorial Health Institute in Poland. The theme of the day, proposed by Mrs Köhler, who is patron of Germany’s Alliance for Chronic Rare Diseases, ACHSE, was rare diseases. A representative from Orphanet Poland was on hand to present information on the Polish and European initiatives for the patients with rare diseases. Mrs Köhler stated that her aim is to bring awareness of orphan diseases to those people not directly affected by them.

    First training programme in genetic counselling now available in Portugal
    A professional Master’s Course in Genetic Counselling is available for the first time in Portugal. Held at the Instituto de Ciências Biomédicas Abel Salazar of the University of Porto, the two-year post-graduation course has been designed for professionals with diverse backgrounds, including psychologists, physicians with other specialties, nurses, and others with an interest in human genetics. The full-time programme will encompass bioethics, epidemiology, genetic counselling principles and techniques, clinical psychology, and features applied internships in the different areas of human genetics, with special emphasis on rare diseases. Applications are being accepted for this year’s programme from 31 August – 18 September. Learn more

    Orphanet News
    A question of honour: Orphanet facilitates HONcode certification for patient associations joining its database
    In order to improve the quality of the information it provides, Orphanet Switzerland has initiated a partnership with the Health On the Net Foundation (HON). Based in Geneva, Switzerland, the HON Foundation promotes and guides the deployment of useful and reliable online health information destined for both patients and medical professionals. Created in 1995, HON is a non-profit, non-governmental organisation, accredited to the Economic and Social Council of the United Nations. For fourteen years, HON has focused on the essential question of the provision of health information to citizens that respects ethical standards. To cope with the unprecedented volume of healthcare information available on the Internet, the HONcode of conduct offers a multi-stakeholder consensus on standards to protect citizens from misleading health information. HONcode is the oldest and the most widely-used code for medical and health related information available on the Internet. The HONcode is designed for both the general public and the web publisher – actively involving website owners in the process of certification through the eight HONcode principles (learn more). Orphanet Switzerland, in its partnership with HON, invites patient organisations listed within its database to certify their website with the HONcode. A link to the HON website is provided for following the free-of-charge application procedure. HONcode membership forms are available in English, French, German, Spanish, Russian, Romanian and Polish. Italian and Portuguese versions will be available soon. Orphanet France has been quick to follow in the footsteps of Orphanet Switzerland and is also facilitating the HONcode application process. Indeed, all Orphanet partner countries are encouraged to follow the initiative. The HONcode is currently used by over 6800 certified websites, covering 118 countries worldwide.

    New Texts
    New Orphanet publications
    Septo-optic dysplasia (in association with the European Journal of Human Genetics)
    Caveolinopathies: from the biology of caveolin-3 to human diseases (in association with the European Journal of Human Genetics)
    Erythropoietic protoporphyria (in the Orphanet Journal of Rare Diseases)


    New Syndromes
    Dominant renin gene mutations associated with early-onset hyperuricemia, anaemia, and chronic kidney failure
    The authors describe three unrelated families with the autosomal-dominant inheritance of early onset anaemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion or the amino acid exchange of a single leucine residue in the signal sequence of renin. Both mutations decrease signal sequence hydrophobicity and are predicted by bioinformatic analyses to damage targeting and cotranslational translocation of preprorenin into the endoplasmic reticulum (ER). It is likely that expression of the mutant proteins has a dominant toxic effect gradually reducing the viability of renin-expressing cells.
    Read the PubMed abstract

    Am J Hum Genet ; 204-213 ; August 2009
    MACS syndrome: macrocephaly, alopecia, cutis laxa, and scoliosis caused by RIN2 deficiency
    Inherited disorders of elastic tissue represent a complex and heterogeneous group of diseases, characterised often by sagging skin and occasionally by life-threatening visceral complications. The authors report an autosomal-recessive disorder that they term MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis). A homozygous frameshift mutation in RIN2 was found to segregate with the disease phenotype in a large consanguineous kindred. The mutation identified results in decreased expression of RIN2, a ubiquitously expressed protein that interacts with Rab5 and is involved in the regulation of endocytic trafficking.
    Read the PubMed abstract

    Am J Hum Genet ; 254-263 ; August 2009
    AGC1 deficiency associated with global cerebral hypomyelination
    The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), specific to neurons and muscle, supplies aspartate to the cytosol and, as a component of the malate-aspartate shuttle, enables mitochondrial oxidation of cytosolic NADH, thought to be important in providing energy for neurons in the central nervous system. The authors describe AGC1 deficiency, a novel syndrome characterised by arrested psychomotor development, hypotonia, and seizures in a child with a homozygous missense mutation in the solute carrier family 25, member 12, gene SLC25A12, which encodes the AGC1 protein. The child had global hypomyelination in the cerebral hemispheres, suggesting that impaired efflux of aspartate from neuronal mitochondria prevents normal myelin formation.
    Read the PubMed abstract

    N Engl J Med ; 489-495 ; 30 July 2009

    New Genes

    Ichthyosis prematurity syndrome: mutations in the fatty acid transport protein 4 gene at cause
    Ichthyosis prematurity syndrome (IPS) is an autosomal-recessive disorder characterised by premature birth and neonatal asphyxia, followed by a lifelong nonscaly ichthyosis with atopic manifestations. Here the authors show that the gene encoding the fatty acid transport protein 4 (FATP4) is mutated in individuals with IPS. These results further emphasise the importance of fatty acid metabolism for normal epidermal barrier function.
    Read the PubMed abstract

    To read more about "Ichthyosis prematurity syndrome"

    Am J Hum Genet ; 248-253 ; August 2009
    Cone photoreceptor disorders: homozygosity mapping reveals PDE6C mutations in early-onset disease
    Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (CD) and complete and incomplete achromatopsia (ACHM). The underlying disease mechanisms of autosomal recessive (ar)CD are largely unknown. The authors identified mutations in the gene PDE6C in patients with cone receptor disorders and show that arCD and ACHM constitute genetically and clinically overlapping phenotypes.
    Read the PubMed abstract

    To read more about "Cone rod dystrophy"
    To read more about "Achromatopsia"

    Am J Hum Genet ; 240-247 ; August 2009
    Metaphyseal anadysplasia: mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum
    The authors report that mutations in either MMP9 or MMP13 are responsible for the human disease metaphyseal anadysplasia, a heterogeneous group of disorders for which a milder recessive variant and a more severe dominant variant are known.
    Read the PubMed abstract

    To read more about "Metaphyseal anadysplasia"

    Am J Hum Genet ; 168-178 ; August 2009
    Congenital myasthenia: identification of an agrin mutation that causes the disease and affects synapse function
    The authors report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction.
    Read the PubMed abstract

    To read more about "Congenital myasthenic syndromes"

    Am J Hum Genet ; 155-167 ; August 2009
    Nonsyndromic deafness and Bartter syndrome: mutations of BSND responsible
    BSND encodes barttin, an accessory subunit of renal and inner ear chloride channels. To date, all mutations of BSND have been shown to cause Bartter syndrome type IV, characterised by significant renal abnormalities and deafness. The authors identified a BSND mutation in four kindreds segregating nonsyndromic deafness. This study demonstrates that BSND mutations with different functional consequences are the basis for either syndromic or nonsyndromic deafness.
    Read the PubMed abstract

    To read more about "Deafness, autosomal recessive, nonsyndromic, sensorineural, type DFNB"

    Am J Hum Genet ; 273-280 ; August 2009
    Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene
    The spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of disorders characterised by degeneration and loss of anterior horn cells in the spinal cord, leading to muscle weakness and atrophy. Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH, also known as pontocerebellar hypoplasia type 1 [PCH1]) is one of the rare infantile SMA variants that include additional clinical manifestations, and its genetic basis is unknown. In a consanguineous family of Ashkenazi Jewish origin the authors identified a nonsense mutation in the vaccinia-related kinase 1 gene (VRK1) as a cause of SMA-PCH. VRK1 is a serine/threonine kinase that phosphorylates p53 and CREB and is essential for nuclear envelope formation.
    Read the PubMed abstract

    To read more about "Pontocerebellar hypoplasia type 1"

    Am J Hum Genet ; 281-289 ; August 2009
    Ophthalmoplegia: a mutation in RRM2B causes the autosomal-dominant progressive external form with multiple mtDNA deletions
    Autosomal-dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disorder that is characterised by accumulation of multiple mitochondrial DNA (mtDNA) deletions in postmitotic tissues. The disorder is heterogeneous, with five known nuclear disease genes that encode the proteins ANT1, Twinkle, POLG, POLG2, and OPA1. Here the authors present a large adPEO family with multiple mtDNA deletions, whose disease was not explained by mutations in any of the known adPEO loci. The authors identified mutations in the RRM2B gene, which encodes the small subunit of the ribonucleotide reductase p53R2, as a cause of multiple mtDNA deletions and adPEO.
    Read the PubMed abstract

    To read more about "Progressive external ophthalmoplegia"

    Am J Hum Genet. ; 290-295 ; August 2009

    Research in Action

    Clinical Research
    Dandy-Walker malformation: FOXC1 is required for normal cerebellar development
    Dandy-Walker malformation (DWM), the most common human cerebellar malformation, has only one characterised associated locus. Here the authors characterise a second DWM-linked locus on 6p25.3, showing that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations including cerebellar vermis hypoplasia (CVH), mega-cisterna magna (MCM) and DWM. FOXC1 heterozygous mutations are known to affect eye development, causing a spectrum of glaucoma-associated anomalies (Axenfeld-Rieger syndrome). The authors report the first brain imaging data from humans with FOXC1 mutations and show that these individuals also have CVH. They conclude that alteration of FOXC1 function alone causes CVH and contributes to MCM and DWM.
    Read the PubMed abstract

    To read more about "Rieger-Axenfeld anomaly"
    To read more about "Dandy-Walker malformation, isolated"
    To read more about "Mega-cisterna magna"

    Nat Genet ; 1037-1042 ; September 2009
    Evaluating access to paediatric cancer care centres in Italy: the TREP project
    A national project focusing on rare malignant paediatric tumors (the TREP project) was launched in Italy in 2000. The present study compared the number of these tumours expected to be diagnosed in Italy with the number of cases actually enrolled in the TREP database in 2000-2006. The predicted number of cases was calculated from incidence data from the Italian network of cancer registries (AIRTum). The TREP database included 336 patients under 18 years, (261 children and 75 adolescents) as compared to 305 and 400 expected cases, respectively. This study shows that the TREP project succeeded in registering and treating the vast majority of the patients under 15 years of age with rare paediatric tumours, demonstrating the feasibility of cooperative protocols even for rare diseases. Conversely, there was a large gap between those registered compared to those expected for adolescents.
    Read the PubMed abstract

    Pediatr Blood Cancer ; 152-155 ; August 2009
    Web resources for rare auto-inflammatory diseases: towards a common patient registry
    To review information resources on rare auto-inflammatory disorders (AIDs) for use by health care professionals, focusing particularly on patient registries, the authors surveyed the websites of several scientific societies of immunology, paediatrics and rheumatology, as well as PubMed and specialised databases. They found that although several resources are now available for rare AIDs, a unique and dedicated site gathering all aspects of these diseases as a whole is still lacking. This study thus advocates a merging of existing patient registries or the creation of a common database.
    Read the PubMed abstract

    Rheumatology ; 665-669 ; June 2009
    Diagnostic Approaches
    Erythrodermas: early skin biopsy helps the diagnosis and management of neonatal and infantile forms
    Erythrodermas are often life-threatening conditions in infants. Determination of the underlying cause is crucial. Microscopic changes in adult erythroderma lack specificity. To determine if an early skin biopsy is helpful for the diagnosis of neonatal and infantile erythroderma, seventy-two patients admitted for erythroderma in the first year of life were retrospectively included in this study. The authors found that skin biopsy is helpful for etiologic diagnosis of early erythroderma of infancy, particularly the most severe diseases (immunodeficiency and Netherton syndrome). Early systematic skin biopsy leads to better and earlier management.
    Read the PubMed abstract

    To read more about "Netherton disease"

    J Cutan Pathol ; Epub ahead of print ; 13 July 2009
    Paraganglioma-phaeochromocytoma syndrome: an immunohistochemical procedure to detect patients with germline mutations
    Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. The authors demonstrate that phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure.
    Read the PubMed abstract

    To read more about "Hereditary pheochromocytoma-paraganglioma syndrome"

    Lancet Oncol ; 764-771 ; August 2009

    Patient Management and Therapy

    Neurofibromatosis type 2: hearing improvement after bevacizumab
    Profound hearing loss is a serious complication of neurofibromatosis type 2, a genetic condition associated with bilateral vestibular schwannomas, benign tumours that arise from the eighth cranial nerve. There is no medical treatment for such tumours. In this study, the authors report that vascular endothelial growth factor blockade with bevacizumab, an anti-VEGF monoclonal antibody, improved hearing in some, but not all, of ten patients with neurofibromatosis type 2. Furthermore, treatment was associated with a reduction in the volume of most growing vestibular schwannomas.
    Read the PubMed abstract

    To read more about "Neurofibromatosis type 2"

    N Engl J Med ; 358-367 ; 23 July 2009
    Huntington disease: patients with neural transplants undergo disease-like neuronal degeneration
    The clinical evaluation of neural transplantation as a potential treatment for Huntington disease (HD) was initiated in an attempt to replace lost neurons and improve patient outcomes. Two of 3 patients with HD who underwent neural transplantation containing striatal anlagen in the striatum a decade earlier, have demonstrated marginal and transient clinical benefits. The authors report in patients with HD that grafts undergo disease-like neuronal degeneration with a preferential loss of projection neurons in comparison to interneurons. Furthermore, immunologically unrelated cells degenerate more rapidly than the patient’s neurons, particularly the projection neuron subtype. These results raise uncertainty about this potential therapeutic approach for the treatment of HD but do provide new opportunities to investigate the underlying mechanisms involved in HD, as well as to explore additional therapeutic paradigms.
    Read the PubMed abstract

    To read more about "Huntington disease"

    PNAS USA ; 12483-12488 ; 28 July 2009
    Leber congenital amaurosis: one year after gene therapy, a patient develops pseudo fovea
    Leber congenital amaurosis (LCA) is a retinal dystrophy and/or dysplasia of prenatal onset. Three young adults with RPE65 mutations received a subretinal injection of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) in one eye. One year later, one of the patients who had reported improvement in visual acuity, unexpectedly developed a pseudo fovea in the treated region. These results reveal the unexpected plasticity of the visual system.
    Consult the PubMed abstract

    To read more about "Leber amaurosis, congenital"

    N Engl J Med ; 725-727 ; 13 August 2009

    Orphan Drugs

    EuropaBio’s annual report reflects its ongoing commitment to rare disease patients
    The European Association for Bioindustries (EuropaBio) was established in 1996 to “provide a voice for the biotech industry at the EU level …[and] … to promote an innovative and dynamic biotechnology-based industry in Europe”. Orphan products figure strongly amongst the medicinal treatments that can benefit from biotechnology. In its 2009 annual report, EuropaBio lists the organisation’s accomplishments and defines future actions. Through its interactions with various bodies such as the European Commission, Parliament, national governments, and EPPOSI, EuropaBio is campaigning for patients’ rights to access life-saving medicines, a harmonisation of the approach to how orphan drugs are assessed, and improved access. Earlier in the year, EuropaBio issued a Healthcare Manifesto for 2009-2010, which includes in its mission statement support for "the European Union in delivering on its vision for access to orphan medicinal products for all patients affected by rare diseases”. The document calls for “creative solutions” in the fields of clinical development, regulatory requirements, and reimbursement - which is particularly urgent at the Member State level. A two-stage reimbursement system is evoked for those products that need further evidence in order to justify reimbursement.
    Consult the EuropaBio annual report
    Consult the EuropaBio Healthcare Manifesto

    International Pompe Association releases results from survey of impact of Myozyme supply disruption
    In July 2008, Genzyme Corporation issued a notification that the worldwide supply of Myozyme® (alglucosidase alfa) would be hindered in 2009 pending the European Commission approval of a larger-scale production facility in Belgium. The International Pompe Association (IPA) worked with Genzyme and a group of expert physicians to form the Myozyme Stakeholders Working Group (MSWG) in order to develop guidelines managing the supply shortage that called for adult patients to reduce one infusion treatment per month. In fact, the disruption to supply was restricted to a single skipped infusion in early 2009 for most adults. However, as many patients reported consequences from the decrease in treatment, the IPA created an informal international survey for the patient community in order to assess the impact of the disruption. The survey also sought to assess the quality of the MSWG guidelines. The results of this survey were published in July and are available on the IPA website. The survey reviews patient response to the communications surrounding the treatment shortage, psychological wellbeing, physical effects, and the return to a normal treatment structure.
    Consult the IPA survey results

    Priority guidelines revised for shortages of Cerezyme
    In response to the closure of a Genzyme production site manufacturing Cerezyme (imiglucerase) for the treatment of Gaucher disease and Fabrazyme (agalsidase beta) for the treatment of Fabry disease, the European Medicines Agency (EMEA) in June 2009 issued a press release recommending priority access for patients most in need of treatment. Genzyme’s Allston Landing site in the USA closed due to viral contamination, resulting in the halt of production of rare disease treatment products Cerezyme and Fabrazyme. On 3 August, Genzyme issued a revised supply management plan and on 14 August, the EMEA issued a corresponding press release. Cerezyme treatment priority will continue to be given to the most vulnerable patients. Under the revised recommendations, these include infants, children, adolescents, and patients with type 2 or type 3 Gaucher disease. These patients should continue to receive Cerezyme at their current dose and frequency. Genzyme has developed a "Cerezyme Emergency Access Program" that allows physicians to request Cerezyme for adult patients with "life-threatening clinical situations". A list of criteria is available that define such situations. Other adult patients will not receive Cerezyme so that supply can be conserved for the most vulnerable cases of the disease.
    View the revised supply management plan for Cerezyme

    Marketing authorisation recommended for two cryopyrin-associated periodic syndrome products at July CHMP meeting
    In July, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted positive opinions, recommending the granting of a marketing authorisation, for two orphan medicinal products. Arcalyst (rilonacept), from Regeneron UK Limited, is indicated for the treatment of adults and children aged 12 years and older with severe symptoms of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS). CAPS is a rare, inherited condition causing recurrent fever, rash and joint pain. Arcalyst is the 57th orphan medicine to receive a positive opinion from the CHMP. The review began on 23 July 2008, with an active review time of 197 days. Ilaris (canakinumab), from Novartis Europharm Ltd., is indicated for the treatment of adults, adolescents and children aged 4 years and older with Cryopyrin-Associated Periodic Syndromes (CAPS), including Muckle-Wells Syndrome (MWS), Neonatal-Onset Multisystem Inflammatory Disease (NOMID) / Chronic Infantile Neurological, Cutaneous, Articular Syndrome (CINCA), and severe forms of Familial Cold Autoinflammatory Syndrome (FCAS). Ilaris is the 58th orphan medicine to receive a positive opinion from the CHMP. The review began on 24 December 2008, with an active review time of 176 days.
    Revlimid receives additional warnings at June CHMP meeting
    Revlimid (lenalidomide) from Celgene Europe Ltd, is indicated for the treatment of multiple myeloma, a malignant neoplasm of plasma cells characterised by overproduction of abnormal plasma cells in the bone marrow and manifested by skeletal destruction, bone pain, and the presence of abnormous immunoglobulins. At the June meeting of the Committee for Medicinal Products for Human Use, several amendments were adopted to sections 4.4 and 4.8 of the Summary of Product Characteristics (SPC) for Revlimid adding warnings concerning "allergic reactions (including hypersensitivity reactions and cross-allergy with thalidomide) and on severe skin reactions following the assessment of the 3rd Periodic Safety Update Report (PSUR). In addition, the existing warning concerning the use of erythropoietic agents was updated with the currently approved threshold of the haemoglobin target level (i.e. 12 g/dl). Hypersensitivity reactions and tumour lysis syndrome were also added as rare adverse reactions in section 4.8 of the SPC. The Package Leaflet has been updated accordingly."
    Authorisation application for hypereosinophilic syndrome product Bosatria withdrawn
    GlaxoSmithKline Research and Development Ltd withdrew its application for marketing authorisation for Bosatria (mepolizumab) to be used in the treatment of hypereosinophilic syndrome in adult patients without the FIP1l1-PDGFR fusion gene. Hypereosinophilic syndromes constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia associated with evidence of eosinophil-induced organ damage. Bosatria was designated as an orphan medicine in July 2004.
    Consult the press release

    The FDA demands cancer warnings for TNF blockers
    The US Food and Drug Administration has required stronger warnings describing potential risks of cancer be included in the packaging information of certain TNF blockers, used to treat juvenile rheumatoid arthritis and other inflammatory diseases. An analysis of reports demonstrates an increased risk of developing cancer in children and adolescents treated with TNF-blockers.


    Second Myotubular Trust call for proposals set to open
    The Myotubular Trust was founded as a charity in 2006 to raise money for research toward a cure and/or treatment for myotubular myopathy. There are three genetically distinct forms of myotubular myopathy. The most common and severe form is x-linked. It usually presents in the newborn period and is characterised by breathing and swallowing difficulties in addition to general muscle weakness. The other forms, either dominant or recessive in inheritance, are usually milder and vary widely.

    The Myotubular Trust announces its second call for proposals for projects focusing on research that would not generally be funded by public or industrial funding sources. This call will be open to European research bodies only. Applications may be made for:
    1. Project grants - Applications will be considered from the Principal Investigator for projects of 2-3 years duration to be carried out by a Post Doctoral researcher, or PHD student
    2. A Myotubular Trust fellowship - Applicants will have identified a host institution and will be undertaking a basic science project of 3-4 years duration. Completed applications will be due mid-December 2009. Awards will likely be made in April 2010. Interested persons should check the Myotubular Trust website for further guidance and the application form, both due to appear shortly.

    NCL-foundation issues call for proposals
    The NCL-Foundation is working to find a cure for Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease. This metabolic neurodegenerative disorder of childhood is inevitably fatal. The gradual stages of suffering are blindness, dementia, epilepsy, loss of speech, paralysis and complete helplessness. The NCL-Foundation is inviting medical and basic science researchers worldwide to submit innovative clinical oriented or translational basic science projects, which can contribute to discovering a cure for juvenile NCL. Scientists from related areas of science, including Alzheimer disease, aging, and other lysosomal storage disorders, are encouraged to apply. Grant monies (50,000 euros) will used for a PhD fellowship undertaking the research project in order to promote the next generation of young NCL research scientists. Application deadline: 31 October 31, 2009. For further details and/or to download the application, visit the NCL-Foundation website

    Partnersearch, Job Opportunities
    Project focusing on in utero cell therapy for SCID, osteogenesis imperfecta and lysosomal diseases seeks partners
    A FP7-Health project aiming to define the best protocol(s) for in utero cell therapy for congenital disorders such as SCID, osteogenesis imperfecta and the lysosomal disorders is seeking to complete its consortium with one or two project partners, of which one SME industrial partner, coming from the new Member State countries and having expertise and interest in this research field.
    For further details


    Courses & Educational Initiatives
    Orphan Europe Academy 2010 programme now available
    The aim of the Orphan Europe Academy is to provide healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration in the field of rare diseases via tailored solutions in training and educational activities. The Orphan Europe Academy 2010 programme is now available online - offering coursework in the areas of metabolic disorders, lysosomal storage diseases, and inborn errors in neonatology.

    What's on Where?

    Adaptive Immunity and the Pathogenesis of Rheumatic Diseases – A Translational Research in Paediatric Rheumatology Conference
    Date: 24–27 September 2009
    Venue: Genoa, Italy

    This third Translational Research in Paediatric Rheumatology conference will showcase the growing body of evidence that the regulation of central and peripheral B and T cell development plays a pivotal role in the pathogenesis of autoimmune diseases, highlighting the molecular and cellular mechanisms involved in the activation of the effector functions of adaptive immunity, their involvement in the pathogenesis of chronic rheumatic diseases, and the potential identification of targets to modulate the activity of the adaptive immune system.
    For further details

    British Paediatric Neurology Association: Rare Disorders Symposium
    Date: 29 September 2009
    Venue: Harrogate, England

    A stand-alone satellite symposium on rare disorders will take place as part of the 8th Paediatric Neurology Conference, exploring a number of themes relating to rare disorders.
    For further details

    Fourth International Conference on Birth Defects and Disabilities in the Developing World
    Date: 4-7 October 2009
    Venue: New Delhi, India

    The theme of the Fourth International Conference is "Translating Research into Cost-effective Services for the Care and Prevention of Birth Defects, Preterm Birth and Consequent Disabilities".
    For further details

    XXth Congress of International Society of Haematology - European and African Division
    Date: 10-13 October 2009
    Venue: Cairo, Egypt

    Including up to date knowledge and the most recent scientific achievements in the field.
    For further details

    ESH Conference on Myelodysplastic Syndromes
    Date: 22-25 October 2009
    Venue: Mandelieu, France

    Covering diagnostics, overlapping syndromes, treatment approaches and more. Deadline for scholarships and abstracts: 15 September 2009
    For further details

    EPPOSI: 10th Workshop on Partnering for Rare Disease Therapy Development
    Date: 26-27 October 2009
    Venue: Brussels, Belgium

    The topic of this year’s workshop of the European Platform for Patients’ Organisations, Science and Industry is “10 years after the adoption of the EU Orphan Medicines Regulation: Where do we go?” Three key themes will be addressed: What is the impact of the economic crisis on the field of rare diseases – and what is the vision on further progress in R&D, diagnosis and patient care? Building on the public policy base of the last 10 years: how to advance policies in the next five years? Rare cancers: specific challenges within rare diseases.
    For further details

    European Society for Phenylketonuria Annual Conference 2009
    Date: 30 October – 1 November 2009
    Venue: Antalya, Turkey

    The conference offers the opportunity to exchange the latest experiences via workshops and presentations. Delegates of member associations will discuss the situation regarding European health politics and European networks. An industrial exhibition will inform on the latest product developments.
    For further details

    TREAT-NMD/NIH International Conference
    Date: 17-19 November 2009
    Venue: Brussels, Belgium

    The aim of the meeting is to share progress in the area of translational medicine in inherited neuromuscular diseases and set the future collaborative agenda. This conference will build on achievements of the NIH and TREAT-NMD. It will be a highly interactive meeting with a strong focus on the key issues surrounding "trial readiness" in the neuromuscular field.
    For further details

    OI in motion: Rehabilitation and Physiotherapy in Osteogenesis Imperfecta
    Date: 20-22 November 2009
    Venue: Rheinsberg, Germany

    Topics include: Rehabilitation of children; rehabilitation of adults; assessments of motor functions; orthoses/mobility aids; and international experiences.
    For further details

    ESF-UB Conference in Biomedicine: Rare Diseases II: Hearing and Sight Loss
    Date: 22-27 November 2009
    Venue: Sant Feliu de Guixols, Spain

    A conference of the European Science Foundation. The meeting will bring together experts in sensory neuroscience, developmental biology, genetics, cell biology, modelling, translational research and therapy. It aims at promoting exchanges between the scientists of the two fields and beyond, at stimulating the emergence of new research projects at the interface between disciplines and at training young researchers in this interdisciplinary field.
    For further details

    International Conference on Myasthenia
    Date: 1-2 December 2009
    Venue: Paris, France

    The conference will bring together research scientists and clinicians from around the world who specialise in myasthenia, to review the latest developments, exchange experiences and ideas, and broaden knowledge and understanding of this rare disease. A session dedicated to the interaction between clinicians, scientists, and patient associations is also scheduled.
    For further details

    2nd Pan-European Conference on Haemoglobinopathies
    Date: 13-14 March 2010
    Venue: Berlin, Germany

    This conference aims to further strengthen the national and regional support networks for thalassaemia patients in Europe, and increase awareness among European medical professionals and national health authorities of the disorder, its proper management and prevention.
    For further details

    18th International Workshop on Vascular Anomalies
    Date: 21-24 April 2010
    Venue: Brussels, Belgium

    The programme for this workshop will be available soon.

    5th European Conference on Rare Diseases 2010
    Date: 13-15 May 2010
    Venue: Crakow, Poland

    Details will be available soon.

    Men 2010: 12th International Workshop on Multiple Endocrine Neoplasia
    Date: 16-18 September 2010
    Venue: Viareggio, Italy

    This two-day meeting will provide a forum for educating basic and clinical investigators on the most recent advances in the area of hereditary endocrine tumours.
    For further details


    Press & Publications

    A sociologist considers the historical development and meaning of the term ‘rare diseases’
    In sociology, the term boundary object describes concepts and/or objects that are stable yet plastic and which can be interpreted differently according to the needs of the user. In an interesting socio-historical paper appearing in the journal Sociology of Health and Illness, the author explores the concept of “rare diseases” as a boundary object and recounts the genesis of the term and its relation to the concepts of orphan and orphan drugs. Asserting that patients and public bodies (versus medical professionals) were decisive in the process of defining the concept of rare diseases, the author observes that “The prevalence-based definition of the category of rare diseases, by allowing distinct and co-ordinated uses, displays the features of a boundary object in this new setting. Two local uses remained unchanged: for the physicians, it still lacks relevance, whereas for the patients, it is a political tool to express their needs, in vivid connection with their illness experience. On the contrary, the adoption of the category elicited a shift in its use for the pharmaceutical industry and public administration. For the former, the strength of the category lies in its connection with the orphan drug status, which is seen as a powerful innovative tool. For the latter, it is a means to attend to public health issues that would have remained invisible otherwise”.
    Consult 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)
    Editor-in-chief: Ségolène Aymé
    Editor: Louise Taylor
    Contact Us
    Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Charlotte Rodwell, Claire Scharf-Kroener, Paloma Tejada, Aurélie Vandeputte
    National Contact Point: Jean Jacques Cassiman (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), Andres Metspalu (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann (Germany), Michael Petersen (Greece), János Sándor (Hungary), Andrew Green (Ireland), Judith Melki (Israel), Bruno Dallapiccola and Domenica Taruscio (Italy), Andre Megarbane (Lebanon), Vaidutis Kucinskas (Lithuania), Alfred Cuschieri (Malta), Abdelaziz Sefiani (Morocco), Martina Cornel (Netherlands), Stein Are Aksnes (Norway), Jolanta Sykut-Cegielska (Poland), Jorge Sequeiros (Portugal), Dragica Radojkovic (Serbia), Ludovit Kadasi (Slovakia), Borut Peterlin (Slovenia), Miguel del Campo and Manuel Posada de la Paz (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Habiba Chaabouni-Bouhamed (Tunisia), Fatmahan Atalar and Ugur Ozbek (Turkey), Edmund Jessop and Idoia Gomez-Paramio (United Kingdom)
    For more information on the Rare Diseases Task Force
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