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Editorial
Following third International Rare Disease Research Consortium workshop, nominations open for the three global Scientific Committees
The third workshop of the International Rare Disease Research Consortium (IRDiRC) was held in Montreal, Canada on 8-9 October 2011, following two previous workshops in Iceland and the USA. The workshop, hosted by the Canadian Institutes for Health Research and Genome Canada and co-organised with the European Commission and the US National Institutes of Health, came just before the 12th International Congress of Human Genetics; making Montreal the place to be in October.
For the third IRDiRC meeting, some 100 international participants representing public and private funding organisations, scientists, regulators, industry, and patient groups were onboard, working together to develop common scientific and policy frameworks that will guide the activities of the participating IRDiRC members. Identifying priority research areas was a principal topic, as well as addressing the regulatory challenges in an international context. Initial goals put forward by the IRDiRC founders include 200 new treatments for rare diseases by the year 2020 and have a diagnosis available for most, if not all, rare diseases. A series of Round Table presentations provided an update of the current and planned actions by the funding agencies committed to IRDiRC.
Nominations for the three IRDiRC Scientific Committees now open
The meeting was also the occasion to discuss establishing a governance structure. Nominations for the three IRDiRC Scientific Committees, encompassing Diagnostics (including sequencing and characterization), Therapies (including pre-clinical and clinical development), and Horizontal Aspects (including ontologies, national history, biobanking, registries etc) are now open. The Scientific Committees will advise the Executive Committee on research priorities for future R&D investments and on progress made of funded research. Specifically, the Scientific Committees will:
Act as scientific coordinating bodies
Propose research priorities for consideration by the Executive Committee
Propose policies and guidelines for adoption by the Executive Committee
Assess progress made by the Working Groups (i.e. projects funded)
Address arising issues of scientific nature
Encourage exchange of protocols and best practices, and agree on standard operating procedures, quality standards, etc
The deadline for submitting a nomination is 15 December 2011
(Learn more).
An Interim IRDiRC Executive Committee meeting is scheduled for January 2012. To be held in Belgium, appointing the members to the IRDiRC Scientific Committees will be a priority at this meeting.
The official report of the third IRDiRC workshop will be released soon. In the meantime, the full agenda, list of participants, and presentations can be viewed on the European Commission’s DG Research and Innovation website.
EUCERD update
EUCERD produces a (freely available) best-seller
The European Union Committee of Experts on Rare Diseases three-part document 2011 Report on the State of the Art of Rare Disease Activities in Europe was released in late summer and announced in OrphaNews Europe in September (learn more). This key report, detailing the rare disease-related activities throughout Europe, has moved to the top of the EUCERD’s most-viewed documents. Since its publication in July, the report has been accessed over 20 000 times. View the report
Spotlight on...
Knock out mouse genome project phenotyping 20,000 genes expected to provide critical insight to understanding rare genetic disease mechanisms
The growing body of exciting, freely accessible data resources available are furthering the understanding of rare disease mechanisms and helping scientists hone their research. One of the most significant resources comes from the International Mouse Phenotyping Consortium (IMPC), which recently announced the launch of its library of mammalian gene function that describes the function of every gene in the mouse genome. The IMPC programme allows researchers from around the world to access all of the resources and information created by the data provided on knockout mice – mice with inactivated genes that help scientists understand what the ‘knocked out’ gene does. By understanding the function of all the mouse genes (of which some 99% have a human equivalent), it is hoped that scientists can improve their understanding of the role genes play in human diseases – including rare conditions. Working with the embryonic stem (ES) cell library created by the International Knock Out Mouse Consortium, the IMPC will take the mutant ES cells and convert them into the mutant mice which will then be phenotyped. The IMPC proposes, in two stages, over the next 10 years to generate mutant mice for 20,000 mouse genes (most of the genes in the mouse genome) and to undertake primary phenotyping of all these mutant mice. The data will be deposited in and disseminated from a central IMPC database. It is hoped that this comprehensive resource will “…substantially shorten the time between basic research and clinical application”. The IMPC is an international consortium involving fifteen research institutions and national funders from six countries, including the Medical Research Council (MRC) Harwell (UK), the National Institutes of Health (US), the Wellcome Trust (UK), the Wellcome Trust Sanger Institute and EMBL-European Bioinformatics Institute in Hinxton (UK), Helmholtz Zentrum München, German Mouse Clinic (Germany), Toronto Centre for Phenogenomics (Canada), Institute Clinique de la Souris (France), Australian Phenomics Network (Australia), RIKEN BioResource Centre (Japan), CNR Monterotondo (Italy), Baylor College of Medicine (USA), University of California Davis (USA), Charles River Laboratories (USA), Children`s Hospital Oakland Research Institute (USA), the Jackson Laboratory (USA), Genome Canada (Canada), MARC Nanjing University (China) and Canadian Institutes of Health Research (Canada).
The IMPC builds upon the successful EUMODIC project (funded by the European Commission under grant LSHG-CT-2006-037188) which developed the operating procedures and IT systems needed to store the vast amounts of data generated, and piloted the production and phenotyping of the mice. IMPC thus builds upon years of planning and technical preparation. In a press release, Dr Paul Flicek, of EMBL-EBI explains that "The open resources created by IMPC will be integrated with many other molecular databases at EMBL-EBI and elsewhere, and benefit from advanced search functionality. This will ensure that researchers can make use of detailed data and high-level summaries of mouse phenotypes and other relevant biological information - for example human disease associations - well into the future".
Dr Bill Skarnes, Senior Investigator at the Wellcome Trust Sanger Institute further explains, "Our drive is to understand the role of genes in disease and use that understanding to improve healthcare. The cells and DNA resources we have developed for IMPC have already proved their value in identifying genes involved in a form of anaemia. The integrated resources delivered by IMPC will make a real difference to researchers' work around the world". Learn more
Other free access data resources mentioned recently in the scientific literature
Other recently-mentioned open access resources that can help further understanding of rare diseases include BioNOT, a searchable database of biomedical negated sentences. Working from the premise that negated biomedical events can be scientifically significant, BioNOT is a database of some 32 million negated sentences that can serve to extract negated events. Using “Rett” as the search term, the BioNOT database provided some 100 text extracts featuring a negated sentence, such as: “In the 10 mentally retarded patients with Rett-like features, however, no mutation was detected in the coding region of MECP2” or “Having Rett syndrome in the ICD-10 PDD category does not make sense” and provides an electronic link to the source of the literature. BioNOT thus allows the user to capture negated events that might be neglected by experts.
Visit BioNOT
Then there is ALFRED. As an
open-access article in the journal Nucleic Acids Research recently described, Yale University-based Alfred is a freely available curated compilation of allele frequency data on DNA sequence polymorphisms in anthropologically defined human populations. Alfred is not a compendium of human DNA polymorphisms, but rather of frequencies of selected polymorphisms with an emphasis on those that have been studied in multiple populations. The data in ALFRED are considered to be in the public domain and available for use in research and teaching. Alfred has allele frequency tables on over 663 400 polymorphic sites to date. Of these, 170 have frequency tables for over 100 different population samples. Records have active links to relevant resources (dbSNP, PharmGKB, OMIM, Ethnologue, etc.). Alfred features flexible search options, data display, and download capabilities, thus allowing easy access to the data.
Learn more about Alfred.
These, along with previously featured projects, such as the Gen2Phen sponsored resources (learn more) are amongst a growing number of free-access sources that are facilitating rare disease knowledge and accelerating the translation from basic to clinical application.
EU Policy News
European Agency for Health and Consumers event reviews EU actions in the field of rare diseases
In late October, the European Agency for Health and Consumers (EAHC) organised a media initiative focused on exploring what is being done at the European level to improve the situation for rare disease patients and their families. The two-day event featured a busy agenda of presentations from some of the main rare disease players in Europe, including pan-European information portal Orphanet and rare disease patient umbrella group Eurordis, as well as a number of projects focusing on individual groups of diseases, and powerful testimonies from patients and their families. The event brought a fresh reminder of the situation millions of rare disease patients grapple with as the momentum for each of the European Union Member States to develop a specific strategy for meeting the needs of its rare disease patients, as put forward in the European Council Recommendation on an action in the field of rare diseases continues. The conference included presentations of some of the activities and initiatives that are funded at the European-level and described how they are contributing to improving the lives of rare disease patients and moving forward the search to better understand and treat this large group of heterogeneous diseases. A ten-minute video, narrated by Commissioner for Health and Consumers Mr John Dalli served to illustrate on a concrete level some of the complex issues rare disease patients and their families face.
Watch the European initiatives for rare diseases video
View the conference presentations and agenda
National & International Policy Developments
Australia’s orphan drug incentives do not extend to biologics
 An informative new article published in the review Pathology outlines Australia’s newly implemented framework for regulating cellular therapies. The country’s Therapeutic Goods Administration in May established a framework for regulating biological-based therapies employing a risk-based classification strategy that requires more comprehensive oversight for more complex treatments. One contentious aspect of the new framework has been the associated costs. Particularly worrying is the lack of an incentive-based mechanism for orphan drugs that would waive fees. As the authors point out, “…the orphan drug scheme which provides fee relief available to sponsors in the US and Europe, and indeed to Australian sponsors producing treatments based upon medicinals, is definitely not available for cell- or tissue-based treatments in Australia”. This apparent oversight is arousing worries that manufacturers of biologics-based treatments will turn to the USA or Europe to develop their products. The authors remark that, “The absence of an orphan scheme for biologicals is astonishing policy as we can be confident that with the small commercial base of these companies many orphan indications will not be supported in Australia and patients will have to seek relief for their diseases in other countries”.
Consult the PubMed abstract
USA’s NIH TRND programme for rare diseases announces new projects to be funded
 In the USA, the National Institutes of Health’s (NIH) Therapeutics for Rare and Neglected Diseases (TRND) programme has announced six new projects to receive funding. The TRND programme takes existing processes for drug development in the pharmaceutical industry as its framework, seeking to improve upon these processes and capitalise on cooperation with academic researchers working on rare and neglected conditions. Created specifically to facilitate the development of new drugs for rare and neglected diseases by bridging the gap in expertise and resources that frequently exists between basic research and the development and testing of new treatments in human subjects, the TRND programme gives the preclinical stage of drug development a much needed boost to get rare or neglected disease treatment development off the ground. The new projects include:
An inhibitor compound for treatment of fibrodysplasia ossificans progressiva
Novel therapy for treatment of creatine transporter deficiency
A compound for treatment of neonatal herpes simplex virus
A drug candidate for treatment of Duchenne muscular dystrophy
A pharmacological therapy for treatment of autoimmune pulmonary alveolar proteinosis
Development of a deuterium-modified compound for treatment of Schistosomiasis
In a press release, NIH Director Francis S. Collins, MD, explained that the selected programmes “… reinforce NIH's commitment to translational research and the need to accelerate potential new treatments that benefit patients with rare and neglected diseases”. TRND projects are applied for via a solicitation process. The next solicitation will open in the spring of 2012. Updated information about solicitations and project information is available on the TRND website .
Other International News
Rare Gems: Australia’s first newsletter for rare diseases
A brand new newsletter with a specific focus on rare diseases launched in October in Australia. Rare Gems will report the latest news in the field of rare diseases and orphan drugs. In the introductory article, Editor Janet Shaw explains that “By sharing gems of information, we hope to connect the rare diseases community, and foster a strong and united voice”. Produced by the National Rare Diseases Coordinating Committee with support from the Office of Population Health Genomics, Rare Gems will provide conference reports, political developments, new publications and more. OrphaNews Europe welcomes this exciting new tool that will help keep the international rare disease community abreast of all the rare disease developments coming from the land down under.
Take a look at Rare Gems
American College of Medical Genetics identifies competencies for clinical geneticists to acquire
A working paper that seeks to identify the competencies needed by the clinical geneticist working in consultation has been made available on the website of the American College of Medical Genetics (ACMG) and is open for comments from ACMG members. The paper presents overarching competencies and corresponding learning objectives and then breaks down the topic by medical specialty for specific competencies, incorporating the rapid developments being driven by advances in technology.
Learn more
Electronic medical records help physicians determine rare disease treatment
Mining, managing and protecting the rich store of data contained in hospital medical records is a hot topic in the field of rare diseases, which suffers from a dearth of information and evidence-based experience. At the Lucile Packard Children’s Hospital in Stanford, California, medical professionals report their experience of exploiting electronic medical records to evaluate a potentially beneficial – yet risky – treatment for a rare condition that has not yet been described in the medical literature. The physicians mined the hospital’s de-identified aggregate records to find relevant cases via the Stanford Translational Research Integrated Database Environment, a platform that acquires and stores all EMR hospital patient data and provides immediate advanced text searching capability. The experience demonstrates the potential of electronic patient records to assist in the diagnosis, treatment and management of rare conditions where existing data is scarce. The case is discussed in the 02 November issue of the New England Journal of Medicine.
Learn more
Two new guides explore creating and maintaining patient registries for rare diseases
 The Specialised Healthcare Alliance (SHCA) is an English coalition of 68 patient-related organisations supported by ten corporate members which campaigns on behalf of people with rare and complex medical conditions. As was reported in the 28 February 2011 issue of OrphaNews Europe, the SHCA issued a report entitled Leaving No One Behind: Delivering High Quality, Efficient Care for People with Rare and Complex Conditions which took stock of recent developments in specialised commissioning and identifies "a series of key drivers in delivering improved care and value for people with rare and complex conditions”. Stemming from the recommendation in this report concerning the central importance of patient registries in specialised care, the SHCA has now produced the Registries Guide 2011. Intended for use by patient organisations - particularly those representing people with rare and complex conditions – the guide seeks to respond to two key questions: Would it be useful and practicable for a particular patient organisation to set up a registry? and What are the key issues that must be taken into account when setting up a registry? The guide also provides tips, case studies and useful links.
Consult the guide
The USA’s Department of Health and Human Services Effective Health Care Program of the Agency for Healthcare Research and Quality also has a document entitled Registries for Evaluating Patient Outcomes: A User’s Guide which has recently been revised to update and expand material. This comprehensive paper is divided into three central sections - Creating, Operating, and Evaluating registries – each of which carefully considers the issues inherent to registry design and function. Applicable to rare and common disease registries, the guide highlights special considerations and needs of rare disease patient registries and uses case examples to illustrate particular topics.
Consult the Registries for Evaluating Patient Outcomes: A User’s Guide
Potential benefits of combining diagnosis and department codes in composite search strategies for rare conditions
 A new study published in the Journal of Clinical Epidemiology looks at the issue of central registry data quality in relation to rare diseases. For the purpose of performing a comprehensive national craniopharyngioma survey covering a recent 20-year period, the authors sought to identify craniopharyngioma diagnosed in Denmark during the period 1985-2004. Because no craniopharyngioma-specific clinical database exists in Denmark, the authors evaluated the sensitivity and validity of a Danish hospital discharge registry for identifying craniopharyngioma patients diagnosed, and also studied the quality of seven craniopharyngioma related diagnosis codes, and tested several combined search strategies, which might be of use in future studies of other rare diseases. The Danish National Patient Registry (NPR), which has existed since 1977, collects systematic information on diagnoses, surgical treatment, and various demographical parameters on all patients admitted to hospital or similar institutions in Denmark. This study found that while the Danish NPR “was a sensitive data source for identifying craniopharyngioma patients … less than one-third of patients identified … had in fact suffered from a craniopharyngioma”. Certain International Classification of Diseases (ICD) codes showed high sensitivities, whereas the positive predictive values were considerably lower. The authors suggest that “Improved validity of the registry output at the cost of acceptable reductions of sensitivity could be obtained by carefully redesigning the search strategy. …[] registration with the best ICD codes, by relevant highly specialized hospital departments, and of neurosurgic procedures are useful search criteria that may be combined to form such successful composite search strategies”.
Consult the PubMed abstract
Ethical, Legal & Social Issues
The first clinical study involving human embryonic stem cells approved in Europe for rare eye condition Stargardt disease
The first clinical trial using human embryonic stem cells has been approved in the European Union. The phase I/II study, which will investigate the safety and tolerance of the novel therapy on a dozen patients in the United Kingdom with rare disease Stargardt macular dystrophy, is being conducted by USA-based company Advanced Cell Technology, after winning approval from the UK Medicines and Healthcare Products Regulatory Agency in September. Stargardt disease typically affects patients aged less than 20 years old, and is a leading cause of juvenile blindness. The trial, using retinal cells derived from human embryonic stem cells, will take place at Moorfields Eye Hospital in London.
Men with disabilities are at increased risk for sexual violence
An article published in the American Journal of Preventive Medicine reminds readers that men with disability can also be victims of sexual violence. Published studies in the field tend to focus more on violence against women. The paper Sexual Violence Victimization Against Men with Disabilities highlights that males with disabilities have a heightened risk for victimization. Rare diseases are responsible for many forms of physical and intellectual disability.
Consult the PubMed abstract
EU Project Follow-up
EpiRare project survey seeks to determine the state-of-the-art of rare disease registries
EpiRare (European Platform for Rare Disease Registries) is a three-year project co-funded by the European Commission within the EU Program of Community Action in the field of Public Health. The adoption of the EU Council Recommendation on an action in the field of rare diseases recommends support of registers and databases for rare diseases and orphan drugs, and is expected to result in a burst of initiatives The EpiRare project seeks to clarify the needs of registries and databases for rare diseases; identify the state-of-the-art of existing registries; and define criteria for quality and harmonisation of registries. EpiRare has launched a survey in order to identify the main activities and needs of rare disease/orphan drug registries. Time is running out to respond to the EpiRare survey and all suitable participants - including stakeholders from both active and expired registries - are urged to contribute their experiences. Preliminary results are already available online.
Learn more about the EpiRare survey
Orphanet News
Orphanet Report Series Prevalence report updated in all languages
The Orphanet Report Series entitled Prevalence of Rare Diseases: Bibliographic Data features prevalence data for over 2000 rare diseases, organised in two formats: by alphabetical order and by decreasing prevalence. The prevalence report has been brought up to date and is available in English, French, German, Italian, Portuguese, and Spanish.
New Texts
New Orphanet Journal of Rare Diseases publications
Neuroacanthocytosis syndromes
Xeroderma pigmentosum
Spinal muscular atrophy
Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease
New Syndromes
Germline BAP1 mutations predispose to melanocytic tumours, malignant mesothelioma, and maybe various other cancers
Two papers describe germline mutations in BAP1 (the gene encoding BRCA1 associated protein-1) in families with multiple members affected by tumours and/or cancers. The first paper presents two families with multiple, skin-colored, elevated melanocytic tumours, with autosomal dominant transmission. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, the authors found inactivating germline mutations of BAP1. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, the authors found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumours.
The authors of the second paper searched for genetic factors predisposing to mesothelioma. They discovered germline BAP1 mutations in two families with a high incidence of mesothelioma, and observed somatic alterations affecting BAP1 in familial mesotheliomas, indicating biallelic inactivation. In addition to mesothelioma, two uveal melanomas and numerous additional cancers were observed in these families. The authors also found germline BAP1 mutations in 2 of 26 sporadic mesotheliomas; both individuals with mutant BAP1 were previously diagnosed with uveal melanoma.
Read the PubMed abstracts
Nat Genet ; 1018-1021; 1022-1025 ; October 2011
A novel entity of clinically isolated adrenal insufficiency caused by a partially inactivating mutation in CYP11A1
The authors describe two brothers (46,XY) who presented with adrenal insufficiency (AI) and normal male genital development. They found both boys have a never published homozygous CYP11A1 mutation, p.R451W. They characterised this novel mutation and found p.R451W had 30% of wild-type activity, consistent with the clinical phenotype in the patients.
Read the PubMed abstract
J Clin Endocrinol Metab ; E1798-E1806 ; November 2011
A new syndrome with ptosis and prominent eyes associated with cleft palate, ear anomalies, and learning disability
The authors report on three patients from two families. Their syndrome includes unusual craniofacial dysmorphism with ptosis, prominent eyes, flat midface, Cupid’s bow configuration of the upper lip, low-set, posteriorly rotated small ears, as well as conductive hearing loss, cleft palate, heart defect, and mild developmental delay. The patients are a mother and her daughter, and an unrelated boy, so the authors suggest this apparently novel clinical entity has an autosomal dominant mode of inheritance.
Read the PubMed abstract
Am J Med Genet ; 2060-2065 ; September 2011
New Genes
Familial predisposition to myelodysplastic syndrome and acute myeloid leukaemia: GATA2 mutations at cause
Read the PubMed abstract
To read more about "Deafness - lymphedema - leukemia"
To read more about "Myelodysplastic syndromes"
Nat Genet ; 929-931; 1012-1017 ; October 2011
46,XX gonadal dysgenesis: a PSMC3IP mutation abolishing coactivation of estrogen-driven transcription responsible in a family
Read the PubMed abstract
To read more about "46,XX gonadal dysgenesis"
Am J Hum Genet ; 572-579 ; October 2011
Neurodegeneration with brain iron accumulation: mutations in C19orf12 cause a distinct recessive clinical subtype
Read the PubMed abstract
To read more about "Neurodegeneration with brain iron accumulation"
Am J Hum Genet ; 543-550 ; October 2011
Deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes: identification of mutations in NFU1 and BOLA3
Read the PubMed abstract
Am J Hum Genet ; 486-495 ; October 2011
Exfoliative ichthyosis: loss-of-function mutations in CSTA underlie congenital autosomal-recessive disease
Read the PubMed abstract
Am J Hum Genet ; 564-571 ; October 2011
Feingold syndrome: identification of germline hemizygous deletions of MIR17HG, encoding a polycistronic microRNA cluster
Read the PubMed abstract
To read more about "Feingold syndrome"
Nat Genet ; 1026-1030 ; 4 September 2011
Isolated trigonocephaly: heterozygous mutations of FREM1 are associated
Read the PubMed abstract
To read more about "Isolated trigonocephaly"
PLoS Genet ; e1002278 ; September 2011
Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis: ARHGAP24 mutations identified
Read the PubMed abstract
To read more about "Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis"
J Clin Invest ; 4127-4137 ; 3 October 2011
Polymicrogyria: compound heterozygous mutations in WDR62 at cause in a sibling pair
Read the PubMed abstract
To read more about "Polymicrogyria"
Am J Med Genet ; 2071-2077 ; September 2011
Recessive holoprosencephaly and septo-optic dysplasia: novel FGF8 mutations responsible in two patients
Read the PubMed abstract
To read more about "Septo-optic dysplasia"
To read more about "Holoprosencephaly"
J Clin Endocrinol Metab ; E1709-1718 ; October 2011
Acute lymphoblastic leukaemias: somatic IL7R gain-of-function mutations found in children
Read the PubMed abstract
To read more about "Acute lymphoblastic leukemia"
Nat Genet ; 932-939 ; October 2011
J Exp Med ; 901-908 ; 9 May 2011
Research in Action
Fundamental Research
Medulloblastoma: human cytomegalovirus (HCMV) has an important role and may be a novel therapeutic target
Read the PubMed abstract
To read more about "Medulloblastoma"
J Clin Invest ; 4033-4055 ; 3 October 2011
Krabbe disease: insights into the disease from structures of murine galactocerebrosidase (GALC) and GALC-product complex
Read the PubMed abstract
To read more about "Krabbe disease"
PNAS ; 15169-15173 ; 13 September 2011
Niemann-Pick disease: NPC1 mutations that abolish cholesterol binding reproduce phenotype of complete NPC1 deficiency in mice
Read the PubMed abstract
To read more about "Niemann-Pick disease type C"
PNAS ; 15330-15335 ; 13 September 2011
Erythropoietic protoporphyria: proposition of a mechanism causing sclerosing cholangitis
Read the PubMed abstract
To read more about "Erythropoietic protoporphyria"
Gastroenterology ; 1509-1519 ; October 2011
Hypokalaemic periodic paralysis: a sodium channel knockin mutant (NaV1.4-R669H) mouse model
Read the PubMed abstract
To read more about "Hypokalemic periodic paralysis"
J Clin Invest ; 4082-4094 ; 3 October 2011
Timothy syndrome: a mouse model recapitulates triad of autistic traits
Read the PubMed abstract
To read more about "Timothy syndrome"
PNAS ; 15432-15437 ; 13 September 2011
Autism spectrum disorder: Cntnap2-/- mice have epilepsy, neuronal migration abnormalities, and core autism-related deficits
Read the PubMed abstract
To read more about "Pervasive developmental disorder"
Cell ; 235-246 ; 30 September 2011
Clinical Research
Congenital herpes virus infection: oral acyclovir suppression improves neurodevelopmental outcomes
Read the PubMed abstract
To read more about "Congenital herpes virus infection"
N Engl J Med ; 1284-1292 ; 6 October 2011
Myelodysplastic syndrome associated with 5q deletion: efficacy of lenalidomide confirmed in a phase 3 study
Read the PubMed abstract
To read more about "Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality"
Blood ; 3765-3776 ; 6 October 2011
Hyper-IgM syndrome type 1: partial immune reconstitution with recombinant CD40 ligand
Read the PubMed abstract
To read more about "Hyper-IgM syndrome type 1"
Blood ; 3811-3817 ; 6 October 2011
Soft-tissue sarcoma: a phase 2 trial of eribulin mesylate showed the drug deserves further study
Read the PubMed abstract
To read more about "Leiomyosarcoma"
To read more about "Synovialosarcoma"
To read more about "Liposarcoma"
Lancet Oncol ; 1045-1052 ; October 2011
Diffuse large B-cell lymphoma: CHOP-like chemotherapy with rituximab improved outcomes for young patients with good-prognosis
Read the PubMed abstract
To read more about "Diffuse large B-cell lymphoma"
Lancet Oncol ; 1013-1022 ; October 2011
Monocytopenia with susceptibility to infections: successful allogeneic haematopoietic stem cell transplantation
Read the PubMed abstract
To read more about "Monocytopenia with susceptibility to infections"
Blood ; 3715-3720 ; 29 September 2011
Uveal melanoma: an online tool to predict survival after treatment
Read the PubMed abstract
To read more about "Uveal melanoma"
Prog Retin Eye Res ; 285-295 ; September 2011
Biliary atresia: cardiomyopathy is a prevalent condition in infants with end-stage cirrhotic liver disease
Read the PubMed abstract
To read more about "Biliary atresia"
To read more about "Cirrhotic cardiomyopathy"
Gastroenterology ; 1264-1272 ; October 2011
Adult T-cell leukaemia/lymphoma: FERM domain mutations induce gain of function in JAK3, with therapeutic perspective
Read the PubMed abstract
To read more about "Adult T-cell leukemia/lymphoma"
Blood ; 3911-3921 ; 6 October 2011
Myelodysplasia: abnormalities of messenger RNA splicing are frequent
Read the PubMed abstract
To read more about "Myelodysplastic syndromes"
Nature ; 64-69 ; 11 September 2011
N Engl J Med ; 1384-1395 ; 13 October 2011
Recessive cognitive disorders: deep sequencing reveals 50 novel candidate genes
Read the PubMed abstract
To read more about "Autosomal recessive nonsyndromic intellectual deficit"
Nature ; 57-63 ; 6 October 2011
Axenfeld-Rieger syndrome: digenic inheritance of mutations in FOXC1 and PITX2 correlating with disease severity in a family
Read the PubMed abstract
To read more about "Axenfeld-Rieger syndrome"
Hum Mutat ; 1144-1152 ; October 2011
Rheumatic diseases: type I interferon pathway is activated in patient subsets with five different diseases
Read the PubMed abstract
To read more about "Systemic sclerosis"
To read more about "Dermatomyositis"
To read more about "Polymyositis"
To read more about "Systemic lupus erythematosus"
Ann Rheum Dis ; 2029-2036 ; November 2011
Takayasu arteritis: pentraxin-3 could be a marker of disease activity
Read the PubMed abstract
To read more about "Takayasu arteritis"
Ann Intern Med ; 425-433 ; 4 October 2011
Stem Cells
Glioblastoma: neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in a mouse model
Read the PubMed abstract
To read more about "Glioblastoma"
Mol Ther ; 1714-1726 ; September 2011
Hyperornithinaemia: optic vesicle-like structures derived from patient cells to facilitate a customised treatment approach
Read the PubMed abstract
To read more about "Hyperornithinemia"
Stem Cells ; 1206-1218 ; August 2011
Duchenne muscular dystrophy: stem cell-mediated transfer of a human artificial chromosome ameliorates the phenotype in mice
Read the PubMed abstract
To read more about "Duchenne muscular dystrophy"
Sci Transl Med ; 96ra78 ; 17 August 2011
Krabbe disease: neural stem cell gene therapy ameliorates pathology and function in a mouse model
Read the PubMed abstract
To read more about "Krabbe disease"
Stem Cells ; 1557-1571 ; October 2011
Gene Therapy
Retinitis pigmentosa: AAV mediated GDNF secretion from retinal glia slows down retinal degeneration in a rat model
Read the PubMed abstract
To read more about "Retinitis pigmentosa"
Mol Ther ; 1602-1608 ; September 2011
SCIDX1: correction of murine disease using a lentiviral vector and a codon-optimised IL2RG gene
Read the PubMed abstract
To read more about "Severe combined immunodeficiency T- B+ due to gamma chain deficiency"
Mol Ther ; 1867-1877 ; October 2011
Pierson syndrome: podocyte-specific Lamβ1 expression in Lamb2(-/-) mice prevents nephrotic syndrome
Read the PubMed abstract
To read more about "Pierson syndrome"
PNAS ; 15348-15353 ; 13 September 2011
Haemophilia A: suppression of immune response to FVIII in mice by transgene modified tolerogenic dendritic cells
Read the PubMed abstract
To read more about "Hemophilia A"
Mol Ther ; 1896-1904 ; October 2011
Therapeutic Approaches
Late infantile neuronal ceroid lipofuscinosis: large-volume intrathecal enzyme delivery increases survival in a mouse model
Read the PubMed abstract
To read more about "Late infantile neuronal ceroid lipofuscinosis"
Mol Ther ; 1842-1848 ; October 2011
Fukuyama congenital muscular dystrophy: SVA retrotransposon causes pathogenic exon-trapping that can be rescued
Read the PubMed abstract
To read more about "Congenital muscular dystrophy, Fukuyama type"
Nature ; 127-131 ; 5 October 2011
Proximal spinal muscular atrophy: peripheral SMN restoration is essential for long-term rescue in a severe mouse model
Read the PubMed abstract
To read more about "Proximal spinal muscular atrophy"
Nature ; 123-126 ; 5 October 2011
Pancreatic ductal adenocarcinoma: inhibiting Cxcr2 disrupts tumour-stromal interactions and improves survival in a mouse model
Read the PubMed abstract
To read more about "Pancreatic carcinoma"
J Clin Invest ; 4106-4117 ; October 2011
Oculocutaneous albinism type 1B: nitisinone improves eye and skin pigmentation defects in model mice
Read the PubMed abstract
To read more about "Oculocutaneous albinism"
J Clin Invest ; 3914-3923 ; October 2011
Systemic sclerosis: edaravone suppresses fibrosis in the bleomycin-induced and tight skin mouse models
Read the PubMed abstract
To read more about "Systemic sclerosis"
Arthritis Rheum ; 3086-3097 ; October 2011
Patient Management and Therapy
Oesophageal and gastric cancer: British-Irish guidelines for disease management
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To read more about "Esophageal adenocarcinoma"
To read more about "Gastric cancer"
To read more about "Esophageal carcinoma"
Gut ; 1449-1472 ; November 2011
Gorlin syndrome: consensus statement from a first international colloquium
The foremost goal of the first international colloquium on basal cell nevus syndrome (BCNS, Gorlin syndrome) was to review and revise the prior diagnostic criteria and define the surveillance recommendations for affected paediatric and adult patients to allow for early intervention. Expert opinion was based on the collective clinical and research experience of the consensus group participants after presentation and review of the previously published literature regarding diagnosis and treatment of BCNS.
Read the PubMed abstract
To read more about "Gorlin syndrome"
Am J Med Genet ; 2091-2097 ; September 2011
Glioblastoma: a systematic review shows limited evidence of intraoperative MRI-guided resection superiority
The authors did this systematic review to address the added value of intraoperative MRI (iMRI)-guided resection of glioblastoma multiforme compared with conventional neuronavigation-guided resection, with respect to extent of tumour resection, quality of life, and survival. 12 non-randomised cohort studies matched all selection criteria and were used for qualitative synthesis. Several limitations and sources of bias were apparent, and the authors concluded that there is only scientific presumption (at best level 2 evidence) that iMRI-guided surgery is more effective than conventional neuronavigation-guided surgery.
Read the PubMed abstract
To read more about "Glioblastoma"
Lancet Oncol ; 1062-1070 ; October 2011
Orphan Drugs
New study pinpoints the winning traits in orphan drug applications that gain marketing authorisation
The surest way not to fail is to determine to succeed. -RB Sheridan
An interesting new study appearing in Drug Discovery Today looks at the factors associated with successful marketing authorisation for orphan medicinal products in the European Union following the implementation of Regulation (EC) No 141/2000, which offers a clutch of incentives for the development of rare disease products. Amongst the elements critical to success emerging from the study are the demonstration of convincing evidence on the primary endpoint and the selection of a clinically relevant endpoint. Other significant factors mentioned include the development plan (particularly having a randomised clinical trial as the pivotal study); sufficient learning (i.e. appropriate dose finding); and medical need, defined as lack of an alternative therapy for the disease, which can positively sway the benefit–risk assessment outcome.
Consult the PubMed abstract
Eleven positive opinions recommending orphan designation at the November COMP meeting
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 11 positive opinions recommending orphan designation at the November 2011 COMP meeting for the treatment of:
- mercury toxicity
- 5q spinal muscular atrophy
- haemophilia B
- cutaneous T-cell lymphoma
- polycythaemia vera
- prevention of the ischaemia/reperfusion injury associated with solid organ transplantation
- prevention of sepsis in at-risk premature infants of less than or equal to 32 weeks of gestational age
- acute myeloid leukaemia
- peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated)
- acute liver failure
- acromegaly
Consult the European Register of Designated Orphan Medicinal Products
Consult the Orphanet list of orphan drugs authorised for marketing in Europe
Almost 30% of the 35 innovative treatments approved in the USA in fiscal year 2011 have orphan indications
In the USA, the Food and Drug Administration (FDA) has published a report of their activity in the realm of innovative medicines. Orphan drugs come out well – making up almost a third of the 35 innovative medicinal products that were approved by the FDA in fiscal year 2011. Moreover, the FDA approved nearly half – 16 – of the innovative drugs under the agency’s “priority review” programme. This scheme accelerates the approval process for drugs that may offer major advances in treatment. The FDA defines innovative medicines as “new molecular entities”, novel chemical structures, including biological products, which have never been approved before to treat any disease, and often represent the most innovative drugs entering the market. Ten of the innovative products approved in fiscal year 2011 have orphan indications.
Consult the FDA FY 2011 Innovative Drug Approvals report
Grants
E-Rare announces joint transnational call for European rare disease research projects driven by young investigators
The aim of the E-Rare ERA-NET on rare diseases call “European Research Projects on Rare Diseases driven by Young Investigators” is to provide to young, independent investigators the opportunity of building transnational collaborations in the field of rare disease research. The transnational project should be based on complementarities and sharing of expertise, demonstrating a clear added value of the cooperation and impact of the expected results on patients affected by rare diseases. Eligible under this call will be young investigators who have been awarded their first PhD/MD or equivalent of doctoral degree since at least 2 and up to 10 years.
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Call for proposals from academic researchers for investigations into the etiology of basal ganglia degeneration in neuroacanthocytosis
Neuroacanthocytosis (NA) diseases are monogenic movement disorders associated with degeneration that begins in the basal ganglia. NA strikes generally in the third or fourth decade with phenotypes resembling Huntington and Parkinson diseases. The NA diseases are characterised by acanthocytic red blood cell membranes. The NA Advocacy seeks to identify the pathway to neurodegeneration in the NA diseases and eventually to find therapies to delay or prevent the development of neuroacanthocytosis and is accepting applications from Principal Investigators not currently pursuing NA research if their specific expertise, together with proof of project feasibility and relevance, can provide novel approaches to the identification of disease mechanisms and therapeutic targets for NA. Grant Proposals may be submitted at any time before 15 January 2012.
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Courses & Educational Initiatives
ESH-ENERCA Training Course: Diagnosis and Management of Very Rare Anaemias
This two-day ENERCA-ESH training course on rare red blood cell disorders will be held in Paris, France on 3-4 February 2012. The course aims at promoting harmonisation of procedures for clinical and biological diagnosis, as well as management and follow-up of patients with very rare red cell disorders, including red blood cell membrane disorders and enzymopathies, congenital dyserythropoietic anaemias, and other rare disorders of the red blood cell. The course should be of interest for biologists, haematologists, paediatricians and trainees in haematology.
For further details
European Cytogeneticists Association Course
The European Advanced Postgraduate Course in Classical and Molecular Cytogenetics is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. Information for the 2012 course (scheduled from 20-28 February) is now available.
For further details
Tenth European Course on the Evaluation of Medicinal Products in Children
Organized with the European Society for Developmental, Perinatal & Paediatric Pharmacology, and the University Rene Descartes Paris V, and taking place from 21-24 February and 27-30 March 2012, modules for this seminar include: Specific aspects of paediatric pharmacology; Issues relating to trials and drug use in children; Drug development and post-marketing surveillance; Pre/peri-natal drug evaluation and use; Paediatric Investigation Plan design; and more.
For further details
Goldrain Courses in Clinical Cytogenetics and Prenatal Genetic Diagnosis
The Goldrain Prenatal Genetic Diagnosis course, tentatively scheduled from 6-12 October 2012 at the Goldrain Castle in South Tyrol (Italy), is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination. The 2012 Clinical Cytogenetics course has not yet been announced.
For further details
Master of Science in Haemoglobinopathy
A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy – such as counsellors, clinical psychologists, nurse specialists and midwives.
For further details
Orphan Academy 2012 Programme
The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
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EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
For further details
What's on Where?
Sanfilippo Foundation Switzerland International Congress
Date: 8-10 December 2011
Venue: Geneva, Switzerland
“Research toward a treatment” is the theme of this conference focusing on innovative research to treat mucopolysaccharidosis.
For further details
2nd Annual Optimising Orphan Drug Development Conference
Date: 18-19 January 2012
Venue: Lyon, France
This commercial event will focus on how to gain access to new geographically markets. It will cover updates on pricing and reimbursement strategies, how to improve clinical trial development plans and examine the challenges faced with paediatric drug development. This conference will also address the role of patient advocacy groups and how to run patient registries efficiently whilst examining novel data capture methods. Understanding how to translate data to clinical trials will accelerate orphan drug development to market, gain market exclusivity thereby keeping companies ahead of competitors.
For further details
VII International Conference on Rare Diseases and Orphan Drugs (ICORD)
Date: 4-6 February 2012
Venue: Tokyo, Japan
A global meeting on international cooperation and public health policies focusing on research, diagnosis, development of and access to treatment and care for rare diseases. The VII ICORD Conference will offer a platform for the exchange of perspectives for medical and healthcare professionals, patients and patients’ groups, basic and clinical researchers, policy-makers, government officers and pharmaceutical, biotechnology and medical device industries.
For further details
Rare Cancers Conference: Improving the Methodology of Clinical Research
Date: 10 February 2012
Venue: Brussels, Belgium
The European Society for Medical Oncology and Rare Cancers Europe have joined forces to present the first Conference addressing the scientific and educational needs of relevant stakeholder groups concerning challenges and potential solutions in the field of clinical research on rare cancers.
For further details
International Congress on Research of Rare and Orphan Diseases
Date: 29 February - 2 March 2012
Venue: Basel, Switzerland
The Swiss-based Blackswan Foundation and Gebert Rüf Stiftung Foundation, both active in supporting research activities in Rare Diseases, are preparing an international congress of which the main topics will include Gene and cell therapy; Stem cells; Diagnostics; Therapeutic applications; and Genomic disorders. The congress will be open to scientific researchers, specialized scholars, professionals and officials.
For further details
Second ASID Congress of the African Society for Immunodeficiencies
Date: 8-11 March 2012
Venue: Hammamet, Tunisia
This second congress – postponed from its original 2011 date - will be an excellent opportunity to strengthen the capacity of colleagues all over the continent to better diagnose and manage patients with PIDs. The commitment and contribution of international experts, societies and associations to this process is highly appreciated.
For further details
13th International Conference on Neuronal Ceroid Lipofuscinosis and 1st Worldwide Meeting of Batten Disease Int'l Alliance
Date: 28-31 March 2012
Venue: London, England
This is the only forum that brings together those with interests in basic science and clinical care for this group of devastating diseases. A new dimension is added this year by bringing together the newly formed Batten Disease International Alliance (BDIA) for its first worldwide meeting. Deadline for abstract submission: 30 November 2011.
For further details
Fourth International Meeting on Primary Central Hypoventilation Syndromes
Date: 13-14 April 2012
Venue: Warsaw, Poland
The fourth international CHS meeting will be organized by the European CHS Consortium and will address physicians, researchers, families and all persons involved or interested in Central Hypoventilation Diseases.
For further details
CILIA 2012 - Cilia in Development and Disease
Date: 16-18 May 2012
Venue: London UK
Sessions will cover: Clinical aspects of ciliopathies and genotype/phenotype prediction; Structure and function of cilia; Role of cilia in development and ciliary signalling modules; Role of cilia in disease – human genetics and animal models; Translational therapy and current and future ciliotherapeutics; and more.
For further details
6th European Conference on Rare Diseases & Orphan Products
Date: 23-25 May 2012
Venue: Brussels, Belgium
The conference is structured in such a way as to demonstrate the importance of EU actions in the field of rare diseases and review progress to date. With its plenary and parallel sessions addressing specific issues, knowledge-sharing is encouraged, the exchange of real experiences and best practices are integrated into the programme, cooperation and networking are stimulated and awareness is increased while ensuring continuity of action and prevention of duplication of efforts. Less advanced regions in this field will benefit from experience sharing with other areas in Europe. The Opening & Plenary Sessions will be interpreted into six languages: English, French, Spanish, German, Dutch and Russian. The date for abstract submissions is 15 January 2012.
For further details
European Human Genetics Conference 2012
Date: 23-26 June 2012
Venue: Nurnberg, Gemany
Symposia include: The molecular basis of facial malformations; Mechanisms and consequences of chromosomal/genetic mosaicism; Primary microcephaly; and much more. Educational sessions include Next-generation sequencing diagnostics; Trinucleotid repeat disorders and more. Plenary sessions include: Targeted pharmacological therapies in genetic disorders (with presentations on Marfan, tuberous sclerosis complex and fragile X); and much more.
For further details
First International Symposium on the Ehlers-Danlos Syndrome
Date: 8-11 September 2012
Venue: Ghent, Belgium
Topics include natural history; clinical aspects; updated nosology; diagnostics guidelines; therapeutic and management strategies; animal models, and more.
For further details
3rd Pan-European Conference on Haemglobinopathies and Rare Anaemias: Towards the Future
Date: 25–26 October 2012
Venue: Limassol, Cyprus
The Thalassaemia International Federation is delighted to announce the organisation of the 3rd Pan-European Conference, held under the auspices of the Cyprus Presidency and in close collaboration with the Cyprus Ministry of Health. The conference will bring together stakeholders to discuss avenues of action to tackle the growing public health burden of chronic and rare diseases in Member States and the EU.
For further details
8th International Prader-Willi Syndrome Conference
Date: 17-21 July 2013
Venue: Cambridge, UK
An opportunity for all involved worldwide in research, working or living with people with PWS to present current research and explore best practice in clinical and day to day management of PWS.
For further details
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30 November 2011
