4 2010

The European Commission announces the appointees of the new European Union Committee of Experts on Rare Diseases
The Official Journal of the European Union on 28 July 2010 published the Commission Decision on the appointment of the expert members of the European Union Committee of Experts on Rare Diseases (EUCERD) culled from the responses to four calls for expression of interest which specified the qualifications and conditions required to become members of the new Committee.

Article 3(4) of Commission Decision 2009/872/EC of 30 November 2009 delineates the establishment of the European Union Committee of Experts on Rare Diseases (EUCERD) consisting of 51 members - including four representatives from patient organisations, four representatives of the pharmaceutical industry, nine representatives of ongoing and/or past Community projects in the field of rare diseases financed by programmes of Community action in the field of health including three members of the pilot European Reference Networks on rare diseases, and six representatives of ongoing and/or past rare disease projects financed by the Community Framework Programmes for Research and Technological Development.

The new appointees hail from the European rare disease information and reference portal Orphanet, European patient organisation EURORDIS, various academic and research institutions throughout Europe, as well as pharmaceutical companies that demonstrate a commitment to developing rare disease products, including Genzyme, Celgene, Orphan Europe, and Baxter.

In addition to these committee members, one representative of each of the 27 Member States is to be appointed by its Member State, along with a representative of the European Centre for Disease Prevention and Control (ECDC) to be appointed by the ECDC.

OrphaNews Europe congratulates all the EUCERD expert appointees and looks forward to reporting on their activities on behalf of European rare disease patients and their families in the near future.
Consult the list of EUCERD expert member appointees

Task Force Update
OrphaNews Europe wishes all its readers a happy summer holiday!

OrphaNews Europe will be back in September. In the meantime, we wish all our readers a relaxing, fun-filled summer.


EU Policy News

Draft proposing guidance for genetically modified cell treatments open for consultation
The draft of the Guideline on Quality, Non-Clinical and Clinical Aspects of Medicinal Products Containing Genetically Modified Cells is open for public consultation until 30 November 2010 on the website of the European Medicines Agency. The guideline “defines scientific principles and provides guidance for the development and evaluation of medicinal products containing genetically modified cells. … Its focus is on the quality, safety and efficacy requirements of genetically modified cells developed as medicinal products. … It is recognised that this is an area under constant development and guidance should be applied to any novel procedures as appropriate”. Genetically modified cells offer hope for the treatment of monogenic inherited diseases – all of which are rare – as well as for certain cancers and other conditions.
Consult the draft guideline


National & International Policy Developments
German court declares legal pre-implantation diagnostics
Germany’s Federal Supreme Court deemed legal the process undertaken by a Berlin-based gynaecologist of disposing of affected artificially-created embryos identified via pre-implantation diagnosis. The embryos, created by in vitro fertilisation, issued from couples with a family history of genetic disease. The gynaecologist actively sought legal clarification on the issue of pre-implantation diagnostics. German law heretofore prohibited the creation of an embryo for any purpose other than pregnancy and Germany is one of a dwindling number of EU countries that outlaws the procedure. Other diagnostic procedures such as amniocentesis are permitted in the country. The German Federal Court stipulated that pre-implantation diagnostics could only be applied for the prevention of genetic disease. The decision has been met with opposition from conservative members of government as well as some patient organisation representatives. It was reported, however, that the German Medical Association embraced the ruling, which would prevent couples at risk for genetic disease from having to travel abroad.
Lean more (in German language)

Swedish language article calls for national distribution scheme for orphan drugs
An article written by representatives of the Swedish Medical Association and published in Lakartidiningen, the Swedish Medical Association’s widely-read weekly paper, asserts that the need for orphan drugs is immense and that their costs are steadily increasing, presenting a problem for the Swedish health care system. Sweden has decentralised health care, divided into 20 counties, which means that just one patient could capsize the budget of a single county. The authors call for discussion on how to resolve this issue and state that prioritisation needs to be made at the national level, as patients have the right to the same treatment, regardless of where in Sweden they live. Consideration of ethical issues is also needed. Furthermore, the authors emphasise the need for an improved system for monitoring the use, follow-up and benefits-assessment of orphan drugs. One recommendation is to give the Swedish Drug Agency the responsibility to gather such information and disseminate it to the community. The article closes by stating that orphan drugs should remain covered under current legislation, by the Dental and Pharmaceutical Benefits Agency. However, the information behind a reimbursement decision needs to be made more transparent.
Canadian Medical Association Journal makes a plea for orphan drug policy
An article in the Canadian Medical Association Journal makes a plea for a policy that would facilitate access to orphan drug treatments. Canada is one of a waning number of developed countries that does not have a scheme for its citizens with rare diseases. In Europe, the Council Recommendation on an Action in the Field of Rare Diseases, which calls on European Union Member States to adopt a strategy by the end of 2013, outlines a comprehensive structure for EU rare disease patients that encompasses epidemiology, research, genetic testing, identifying and/or creating networks and centres of expertise, information, education - and treatment.
OECD guidelines for human biobanks and databases tailored for Western Australian establishments
In Western Australia, the Guidelines for Human Biobanks, Genetic Research Databases and Associated Data have been published to provide "principles and best practices for the establishment, governance, management and use of human biobanks, genetic research databases and associated data used for research purposes". Prepared by the Office of Population Health Genomics, the guidelines lean heavily on the 2009 OECD Guidelines on Human Biobanks and Genetic Research Databases "with some modifications to take account of the domestic context, stakeholder and community views, and laws". Definitions are included for relevant terminology and the document concludes with a handy "checklist" of 47 points summarising the recommendations.
Other European news
From Russia with love - the country’s very first conference for rare diseases takes place
The Fifth Eastern European Conference for Rare Diseases and Orphan Drugs took place alongside the First All Russian Conference for Rare Diseases and Rarely Used Medical Technologies in Saint Petersburg, Russia, in early July, organised jointly by Russian umbrella patient organisation Genetika with support from Orphanet-Bulgaria country partner and leader of the National Alliance of People with Rare Diseases Bulgaria. A plenary session on the general topic of rare diseases and orphan drugs filled the agenda on the first day. A roster of quality speakers was present: Kerstin Westermark of the European Medicines Agency presented the outcome of the Orphan Drug regulation; Alberto Volpato from DG Sanco and Catherine Berens from DG Research presented the European Commission programmes to support rare diseases; and several national experiences were presented in detail, including Ségolène Aymé for France, Domenica Taruscio for Italy, Rumen Stefanov for Bulgaria, Sonja van Weely for The Netherlands, and Edmund Jessop for Great Britain. The following days were oriented toward the practical diagnosis and management of certain groups of diseases, mainly those with innovative treatments available. Besides Genetika, the conference venue allowed for the meeting of other Russia-based patient organisations. The Rare Diseases Working Group, coordinated by Irina Myasnikova, a geneticist working in Moscow and affiliated with Genetika, held a meeting. Several well-established patient organisations were in attendance. The three-day event also proved fruitful in broaching the possibility of extending Orphanet, the pan-European information portal for rare diseases and orphan drugs, to the Russian language, as well as to the inclusion of information on Russia-based resources. Indeed, an expert from the Research Centre for Medical Genetics of the Russian Academy of Medical Sciences expressed a keen interest.
First Orphan Designation Dossier support grants awarded to two small Dutch bio-pharmaceutical companies
To help stimulate the development of orphan drugs, WGM, the Dutch Steering Committee on Orphan Drugs, is offering a small subsidy for the costs of writing and submitting the Orphan Designation Dossier (ODD) to the European Medicines Agency to small- and medium-sized Dutch enterprises. The first ODD-support grant has been awarded to enterprise DNage for its product Prodarsan, currently under development for the treatment of Cockayne syndrome. A second ODD-support subsidy was awarded to to-BBB technologies for glutathionepegylated liposomal doxorubicine hydrochloride (2B3-101), being developed as a treatment for brain cancer including glioma. In a press release, Remco de Vrueh, Orphan Product Developer for the Dutch Steering Committee observed that "Both products are prime examples of a number of novel innovative medicinal products that are currently being developed by the small and medium-sized bio-pharmaceutical industry in the Netherlands, many of which are directed to rare, but life-threatening or chronically debilitating disorders". The ODD-support scheme is an initiative of the Dutch Steering Committee on Orphan Drugs and is executed by the Netherlands Organisation for Health Research & Development (ZonMw).

Orphanet News
Orphanet annual activity report available in Spanish and French languages
As reported last month, Orphanet, the reference portal for rare diseases and orphan drugs with partnerships in 38 pan-European countries, published online its annual activity report for 2009, delineating the diverse activities of the network. This document is also available in Spanish language as well as in French.

New Texts
New Orphanet Journal of Rare Diseases publications
Hereditary combined deficiency of the vitamin K-dependent clotting factors

New Syndromes

A new ocular syndrome with megalocornea, spherophakia, and secondary glaucoma has LTBP2 null mutations
The authors report two families with children from healthy, consanguineous parents presenting with megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, features associated with Marfan syndrome. Glaucoma was not present at birth, but was diagnosed in older children. Homozygous truncating mutations of the LTBP2 gene were found in patients from both families. Intraocular pressures should be followed-up in young children with an ocular phenotype consisting of megalocornea, spherophakia and/or lens dislocation, LTBP2 gene analysis is recommended in these patients.
Read the PubMed abstract

Eur J Hum Genet ; 761-767 ; July 2010
A new condition combines West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay
The authors describe four individuals with early-onset West syndrome, severe hypomyelination, poor visual attention, and developmental delay. A de novo 9q33.3-q34.11 microdeletion involving STXBP1 was found in one patient. SPTAN1 mutations were identified in two others.
Read the PubMed abstract

Am J Hum Genet ; 881-891 ; 11 June 2010
Myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities in a patient with a dystroglycan gene deletion
Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin alpha2). In this study, the authors describe a patient with a heterozygous de novo deletion of a 2-Mb region of chromosome 3, which includes the dystroglycan gene (DAG1). The patient is a 16-year-old female with learning difficulties, white matter abnormalities, elevated serum creatine kinase, oral-motor dyspraxia and facial hypotonia but minimal clinically significant involvement of other muscles.
Read the PubMed abstract

Eur J Hum Genet ; 852-855 ; July 2010

New Genes

Hoyeraal-Hreidarsson syndrome: unique Apollo splice variant identified
Impaired telomere protection in humans causes dyskeratosis congenita, of which Hoyeraal-Hreidarsson (HH) syndrome is a severe form, characterised by premature aging, bone marrow failure, and immunodeficiency. The authors identified a unique Apollo splice variant (designated Apollo-Delta) in fibroblasts from a patient with HH syndrome. Apollo-Delta generates a dominant negative form of Apollo lacking the telomeric repeat-binding factor homology binding motif required for interaction with the shelterin TRF2 at telomeres. Apollo-Delta hampers the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome.
Read the PubMed abstract

To read more about "Hoyeraal-Hreidarsson syndrome"

PNAS USA ; 10097-10102 ; 1 June 2010
Ochoa syndrome: Loss-of-function mutations in HPSE2 at cause
Two articles appearing in the American Journal of Human Genetics report on the urofacial syndrome (also known as Ochoa syndrome), a rare autosomal recessive disease characterised by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. Both groups identify Heparanse 2 (HPSE2) as the culprit gene for the syndrome. HPSE2 encodes a 592 aa protein that contains a domain showing sequence homology to the glycosyl hydrolase motif in the heparanase HPSE gene, but its exact biological function has not yet been characterised.
Read the first PubMed abstract
Read the second PubMed abstract

To read more about "Ochoa syndrome"

Am J Hum Genet ; 957-962 ; 11 June 2010
Am J Hum Genet ; 963-969 ; 11 June 2010

Sensenbrenner syndrome is a ciliopathy caused by mutations in the IFT122 gene
Sensenbrenner syndrome, also known as cranioectodermal dysplasia (CED), is a disorder characterised by craniofacial, skeletal, and ectodermal abnormalities. Most cases reported to date are sporadic, but a few familial cases support an autosomal-recessive inheritance pattern. The authors identified a homozygous missense mutation in the IFT122 gene. Because not all patients harboured mutations in IFT122, CED seems to be genetically heterogeneous, but this study suggests that the causative mutations in the unresolved cases most likely affect primary cilia function too.
Read the PubMed abstract

To read more about "Sensenbrenner syndrome"

Am J Hum Genet ; 949-956 ; 11 June 2010
Lymphedema: GJC2 missense mutations at cause
Lymphedema is the clinical manifestation of defects in lymphatic structure or function. The authors describe six probands with unique missense mutations in GJC2. They hypothesize that missense mutations in GJC2 alter gap junction function and disrupt lymphatic flow. The identification of GJC2 mutations as a cause of primary lymphedema raises the possibility of novel gap-junction-modifying agents as potential therapy for some forms of lymphedema.
Read the PubMed abstract

To read more about "Lymphedema"

Am J Hum Genet ; 943-948 ; 11 June 2010
Congenital heart defects: haploinsufficiency of TAB2 at cause
Congenital heart defects (CHDs) are the most common major developmental anomalies and the most frequent cause for perinatal mortality, but their aetiology often remains obscure. The authors identified the TGF-beta-activated kinase 1/MAP3K7 binding protein 2 gene TAB2 in patients. A balanced translocation was identified, cosegregating with familial CHD. Mapping of the breakpoints demonstrated that this translocation disrupts TAB2.
Read the PubMed abstract

To read more about "Congenital heart malformation"

Am J Hum Genet ; 839-849 ; 11 June 2010
Long QT syndrome: identification of a Kir3.4 mutation in the congenital form
Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the aetiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene.
Read the PubMed abstract

To read more about "Familial long QT syndrome"

Am J Hum Genet ; 872-880 ; 11 June 2010

Research in Action

Fundamental Research
Leigh syndrome: complex I deficiency due to loss of Ndufs4 in the brain at cause
To explore the lethal, ataxic phenotype of complex I deficiency in Ndufs4 knockout mice, the authors inactivated Ndufs4 selectively in neurons and glia. Their findings suggest that dysfunctional complex I in specific brain regions results in progressive glial activation that promotes neuronal death that ultimately results in mortality.
Read the PubMed abstract

To read more about "Leigh syndrome"

PNAS USA ; 10996-11001 ; 15 June 2010
Epidermolysis bullosa: a mouse model of the generalised non-Herlitz junctional form
Epidermolysis bullosa (EB) is a class of intractable, rare, genetic disorders characterised by fragile skin and blister formation as a result of dermal-epidermal mechanical instability. EB presents with considerable clinical and molecular heterogeneity. The authors identified a spontaneous, autosomal recessive mutation (Lamc2(jeb)) due to a murine leukaemia virus long terminal repeat insertion in Lamc2 (laminin gamma2 gene) that results in a hypomorphic allele with reduced levels of LAMC2 protein. These mutant mice develop a progressive blistering disease validated at the gross and microscopic levels to closely resemble generalised non-Herlitz JEB. The Lamc2(jeb) mice display additional extracutaneous features such as loss of bone mineralisation and abnormal teeth, as well as a respiratory phenotype that is recognised but not as well characterised in humans. This model faithfully recapitulates human JEB and provides an important preclinical tool to test therapeutic approaches.
Read the PubMed abstract

To read more about "Junctional epidermolysis bullosa, non-Herlitz type"

J Invest Dermatol ; 1819-1828 ; July 2010
Clinical Research
Rubinstein-Taybi syndrome: high frequency of copy number imbalances in patients negative to CREBBP mutational analysis
Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant disorder characterised by facial dysmorphisms, growth and psychomotor development delay, and skeletal defects. The known genetic causes are point mutations or deletions of the CREBBP (50-60%) and EP300 (5%) genes. To detect chromosomal rearrangements indicating novel positional candidate RSTS genes, the authors used a-CGH to study 26 patients fulfilling the diagnostic criteria for RSTS who were negative at fluorescence in situ hybridisation analyses of the CREBBP and EP300 regions, and direct sequencing analyses of the CREBBP gene. They found seven imbalances (27%): four de novo and three inherited rearrangements not reported among the copy number variants.
Read the PubMed abstract

To read more about "Rubinstein-Taybi syndrome"

Eur J Hum Genet ; 768-775 ; July 2010
Primary biliary cirrhosis: low bone mass and severity of cholestasis affect fracture risk in patients
The influence of osteoporosis and liver disease on fracture risk is not well characterised in patients with primary biliary cirrhosis (PBC). The authors studied a large series of women with PBC to assess the prevalence and risk factors for fractures and the fracture threshold. Fractures, particularly vertebral fractures, are associated with osteoporosis, osteopenia, and T scores less than -1.5, whereas osteoporosis and osteopenia are associated with the severity of liver damage. Patients with T scores less than -1.5 might require additional monitoring and be considered for therapy to prevent fractures.
Read the PubMed abstract

To read more about "Primary biliary cirrhosis"

Gastroenterology ; 2348-2356 ; June 2010
Bardet-Biedl syndrome: a role for dominant negative and common alleles in oligogenic forms
The authors present a systematic approach, grounded on physiologically relevant assays, to evaluate the mutational content (125 alleles) of the 14 genes associated with Bardet-Biedl syndrome (BBS). A combination of in vivo assays with subsequent in vitro validation suggests that a significant fraction of BBS-associated mutations have a dominant-negative mode of action. A subset of common alleles, previously considered to be benign, is, in fact, detrimental to protein function and can interact with strong rare alleles to modulate disease presentation.
Read the PubMed abstract

To read more about "Bardet-Biedl syndrome"

PNAS USA ; 10602-10607 ; 8 June 2010
Gene Therapy
Haemophilia B: peripheral transvenular delivery of adeno-associated viral vectors to skeletal muscle
Muscle represents an important tissue target for adeno-associated viral (AAV) vector-mediated gene transfer of the factor IX (FIX) gene in haemophilia B (HB) subjects with advanced liver disease. Previous studies of direct intramuscular administration of an AAV-FIX vector in humans showed limited efficacy. Here the authors adapted an intravascular delivery system of AAV vectors encoding the FIX transgene to skeletal muscle of HB dogs. The procedure, performed under transient immunosuppression (IS), resulted in widespread transduction of muscle and sustained, dose-dependent therapeutic levels of canine FIX transgene up to 10-fold higher than those obtained by intramuscular delivery. Correction of bleeding time correlated clinically with a dramatic reduction of spontaneous bleeding episodes. None of the dogs receiving the AAV vector under transient IS developed inhibitory antibodies to canine FIX; transient inhibitor was detected after vector delivery without IS.
Read the PubMed abstract

To read more about "Hemophilia B"

Blood ; 4678-4688 ; 10 June 2010
Congenital achromatopsia: gene therapy rescues cone function
In this study, the authors demonstrate that rAAV-mediated gene replacement therapy with different forms of the human red cone opsin promoter led to the restoration of cone function and day vision in two canine models of CNGB3 achromatopsia, a neuronal channelopathy that is the most common form of achromatopsia in man. The robustness and stability of the observed treatment effect was mutation independent, but promoter and age dependent. Subretinal administration of rAAV5-hCNGB3 with a long version of the red cone opsin promoter in younger animals led to a stable therapeutic effect for at least 33 months.
Read the PubMed abstract

To read more about "Achromatopsia"

Hum Mol Genet ; 2581-2593 ; 1 July 2010
Therapeutic Approaches
Lamellar ichthyosis: interleukin-1 alpha blockade prevents hyperkeratosis in an in vitro disease model
The autosomal recessive congenital ichthyoses are a family of related diseases causing a severe defect in the barrier function of the epidermis. Neonates are usually born as collodion babies, but later form scales characteristic of the disease, due to a combination of thickening of the cornified layer and an increase in the production of non-polar lipids. Current treatments of choice are exfoliative creams and moisturizing agents and the use of oral retinoids. The skin condition and treatment impact significantly on quality of life and, with oral retinoids, there are potential complications associated with long-term use. The authors created an in vitro organotypic culture model that closely mimics the disease. Interleukin-1 alpha (IL1A) expression was increased and there was a lack of loricrin cross-linking. All patients tested had an increased IL1A and treatment of wild-type organotypic cultures with IL1A was sufficient to induce hyperkeratosis. Treatment of disease mimic organotypic cultures with IL-1 receptor antagonist led to a dose-dependent decrease in hyperkeratosis without a reduction in non-polar lipids in the cornified layer, which has the potential to reduce scaling without the requirement to constantly apply emollients.
Read the PubMed abstract

To read more about "Lamellar ichthyosis"

Hum Mol Genet ; 2594-2605 ; 1 July 2010
Gaucher disease: comparative therapeutic effects of velaglucerase alfa and imiglucerase in a mouse model
Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid beta-glucosidase (GCase). Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bone manifestations. Here, similar in vitro enzymatic properties, and in vivo pharmacokinetics and pharmacodynamics (PK/PD) and therapeutic efficacy of GCase were found with two human GCases, recombinant GCase (CHO cell, imiglucerase, Imig) and gene-activated GCase (human fibrosarcoma cells, velaglucerase alfa, Vela), in a Gaucher mouse.
Read the PubMed abstract

To read more about "Gaucher disease"

PLoS One ; e10750 ; 20 May 2010
Diagnostic Approaches

Hypogonadotropic hypogonadism: measuring basal follicle-stimulating hormone after GnRH infusion confirms diagnosis
Differential diagnosis between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty in boys is challenging. Most tests use an acute GnRH stimulus, allowing only the release of previously synthesised gonadotropins. The authors evaluated the diagnostic accuracy of basal and peak gonadotropins after GnRH infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH. Basal FSH less than 1.2 IU/liter confirms HH, which precludes from further testing, reducing patient discomfort and healthcare system costs. In patients with basal FSH of at least 1.2 IU/liter, a GnRH infusion test has a high diagnostic efficiency.
Read the PubMed abstract

To read more about "Congenital hypogonadotropic hypogonadism"

J Clin Endocrinol Metab ; 2811-2818 ; June 2010

Patient Management and Therapy

Squamous-cell carcinoma of the head and neck: an accelerated schedule of radiotherapy more effective
Several large randomised studies from Western Europe and the USA have shown that accelerated fractionation of radiotherapy might be beneficial in the treatment of squamous-cell carcinoma of the head and neck (HNSCC). The aim of this study was to determine whether accelerated fractionation could be applied in developing countries, where there are fewer therapeutic resources and where tumour burdens can be heavier. Between Jan 6, 1999, to March 31, 2004, nine centres from Asia, Europe, the Middle East, Africa, and South America recruited patients with HNSCC of the larynx, pharynx, and oral cavity who were eligible for curative radiotherapy. Patients were randomly assigned in this open-label trial to receive an accelerated regimen of six fractions of radiotherapy per week (n=458) or to receive a conventional radiotherapy regimen of five fractions per week (n=450). Patients were stratified by tumour localisation, T classification, histopathological grade, and institution. An accelerated schedule of radiotherapy for HNSCC was more effective than conventional fractionation, and since it does not require additional resources, might be a suitable new worldwide standard baseline treatment for radiotherapy of HNSCC.
Read the PubMed abstract

To read more about "Squamous cell carcinoma of head and neck"

Lancet Oncol ; 553-560 ; June 2010
Pycnodysostosis: near normalisation of adult height and body proportions via growth hormone
Pycnodysostosis is a genetic lysosomal storage disease characterised by osteosclerosis of the skeleton, short stature and brittle bones: The authors report a pilot open study of three children with pyknodysostosis and 16 age-matched children with idiopathic short stature (ISS) treated with a similar IGF-I-based dosing of GH therapy. Pyknodysostotic patients reached near-normal stature and skeletal proportions with a personalised GH treatment targeted at appropriate IGF-I levels. Remarkably, body disproportion was largely corrected by GH treatment.
Read the PubMed abstract

To read more about "Pycnodysostosis"

J Clin Endocrinol Metab ; 2827-2831 ; June 2010
Juvenile idiopathic arthritis: impact of administration route on intracellular methotrexate polyglutamate concentrations
Intracellular methotrexate (MTX) polyglutamates (MTXGlu) have been shown to be potentially useful biomarkers of clinical response in adult patients with rheumatoid arthritis. The present study was undertaken to measure intracellular MTXGlu concentrations in a cohort of patients with juvenile idiopathic arthritis (JIA) to determine the predictors of MTXGlu variability in these patients. MTX was administered subcutaneously in 66 patients (67%). Fifty-six patients (57%) had active arthritis at the time of the clinic visit. In this cohort of patients with JIA, the MTXGlu total concentration varied 40-fold. The route of MTX administration contributed to the variability in concentrations of MTXGlu.
Read the PubMed abstract

To read more about "Idiopathic juvenile osteoporosis"

Arthritis Rheum ; 1803-1812 ; June 2010

Orphan Drugs

Shire acquires strategic location for rare disease product development
Biopharmaceutical company Shire Plc has announced the strategic purchase of the Lexington Technology Park campus in Massachusetts. The acquisition signifies "an investment in the growth of its Human Genetic Therapies business, which focuses on the discovery, development and manufacturing of treatments for rare genetic diseases". Lexington, Massachusetts is a hub for biomedical technology.
Fifteen new orphan designations from the COMP in July
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 15 positive opinions issued at the July 2010 COMP meeting for the treatment of:

- medulloblastoma
- Cushing syndrome
- cowpox infection
- monkeypox infection
- variola infection
- mantle cell lymphoma
- hepatocellular carcinoma
- idiopathic pulmonary fibrosis
- moderate or severe closed traumatic brain injury
- small cell lung cancer
- Friedreich ataxia
- primary myelofibrosis
- Hodgkin lymphoma
- amyotrophic lateral sclerosis
- Behcet disease

Consult the European Register of Designated Orphan Medicinal Products
Consult the Orphanet list of orphan drugs authorised for marketing in Europe


What's on Where?

The Tuebingen Outer Retina Conference
Date: 29-31 August 2010
Venue: Tuebingen, Germany

The conference focus is on the outer retina, the bipolar cells, and associated disorders. Sessions will cover genetic, anatomic, and neurophysiologic aspects, pathophysiology and diagnostics in inherited and light-induced retinal degenerations, animal models, and therapeutic strategies.
For further details

2nd Congress of the European Society for Paediatric Anaesthesiology
Date: 2-4 September 2010
Venue: Berlin, Germany

Amongst the programme of this congress will be a session entitled “Rare diseases: a common problem!” featuring the anaesthetic management of a child with a rare disease; approaches to rare diseases at the national and European level; and the OrphanAnaesthesia project.
For further details

International Society for Cellular Therapy (ISCT Europe) Second Regional Meeting
Date: 11-14 September 2010
Venue: Belgirate, Italy

The ISCT is the global forum and resource for developing and supporting innovative cellular therapies through communication, education, and training, thus furthering clinical based investigation for the benefit of patients. Topics of this European regional meeting will include hematopoietic stem cells, mesenchymal stromal cells, immunotherapy, gene therapy, tissue engineering, new emerging therapies, legal and regulatory affairs, prenatal issues: cord blood, placenta and umbilical cord.
For further details

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

Second AnEUploidy Workshop
Date: 17-19 September 2010
Venue: Split, Croatia

AnEUploidy is the acronym of an Integrated Project (IP) funded by the European Commission within its Sixth Framework Programme. This project aims to contribute to the understanding of the molecular basis and pathogenic mechanisms of aneuploidies. This second workshop will allow colleagues to share views, advancements, and ideas.
For further details

International Data Sharing Conference
Date: 20-22 September 2010
Venue: Oxford, UK

This international three day conference is organised by the Centre for Health, Law and Emerging Technologies at the University of Oxford. It will address the implications of data sharing in research and how it should be effectively governed. The conference will bring together a wide range of voices to discuss and think more deeply about the technological, legal, ethical, and social challenges raised by research data sharing. There will be a satellite workshop on ethical and philosophical issues arising from data sharing.
For further details

2nd Conference on Clinical Research for Rare Diseases
Date: 21 September 2010
Venue: Bethesda, MD, USA

Sponsored by the Rare Diseases Clinical Research Network and the Clinical and Translational Science Awards, this unique conference will focus on research methodology for rare diseases and should be of particular interest to trainees and junior faculty engaged in research in rare diseases.
For further details

EFGCP Children’s Medicines Working Party and DIA Europe Second Joint Paediatric Conference
Date: 28-29 September 2010
Venue: London, UK

The European Forum for Good Clinical Practice (EFGCP) Children’s Medicines Working Party and DIA Europe are pleased to announce their second joint paediatric conference. Traditional paediatric meetings of both societies in the past and the joint meeting in 2009 have attracted top level speakers from the European Medicines Agency (EMA), FDA, national authorities, WHO, academia, pharmaceutical industry and parents & patients’ organisations. This second joint program will again offer the opportunity for intensive discussion among stakeholders in different topics relevant for paediatric medicines: visions, daily challenges and ways forward in paediatric drug development.
For further details

First European Conference on Lymphangioleiomyomathosis (LAM)
Date: 1-3 October 2010
Venue: Udine, Italy

This conference provides an unprecedented experience to learn about scientific updates across various fields and the latest results on recent drug trials. In addition, representatives from many LAM associations across the world will attend to learn from each others’ experiences on how to gather patients, promote involvement in the LAM community and raise awareness.
For further details

International Meeting on Fibrous Dysplasia of Bone/McCune-Albright Syndrome: Best Clinical Practice and Future Research
Date: 3-5 October 2010
Venue: Bethesda, Maryland, USA

This conference will gather experts to develop a consensus on the best current medical and surgical treatment of fibrous dysplasia, MAS and Cherubism, to define areas of focus for future research, and to establish parameters for a registry/bio repository to aid research. Participants in the meeting include paediatric and adult orthopaedic specialists, cranio facial surgery, plastic surgery, endocrinology, and specialists in stem cells, microbiology and pathology from the USA, Israel, Italy, and Taiwan.
For further details

XIV Meeting of the European Society for Immunodeficiencies and IX Meeting of the Int’l Nursing Group for Immunodeficiencies
Date: 6-9 October 2010
Venue: Istanbul, Turkey

Featuring an interesting scientific programme of clinical, laboratory and molecular findings, diagnosis, prevention and treatment for common and rare primary immunodeficiencies. Held in tandem with the XIth Meeting of the International Patient Organisation for Primary Immunodeficiencies.
For further details

Sixth International Network of Paediatric Surveillance Units (INoPSU) Meeting
Date: 7 October 2010
Venue: Dublin, Ireland

The INoPSU joins 12 diverse countries with a common purpose - to conduct surveillance of uncommon conditions of childhood. The member units span the globe - from Canada to New Zealand. This year’s keynote address will be from Orphanet.
For further details

2nd European Rett Syndrome Conference
Date: 7-10 October 2010
Venue: Edinburgh, Scotland

Sessions include clinical and molecular update on MECP2 and Rett Syndrome; non coding RNAs & brain development; lessons from other diseases and other models; treatments and trials; outcome measures, international collaborations; and current perspectives and next steps.
For further details

15th International Congress of World Muscle Society
Date: 12-16 October 2010
Venue: Kumamoto, Japan

The main topics to be addressed include new therapeutic targets for neuromuscular disorders; congenital muscular dystrophies (celebrating the 50th anniversary of Fukuyama congenital muscular dystrophy); and distal myopathies and protein aggregation myopathies.
For further details

26th Annual Meeting of the Histiocyte Society
Date: 18–20 October 2010
Venue: Boston, Massachusetts USA

This year’s scientific programme will feature presentations by several experienced researchers regarding a variety of perspectives on the histiocytic disorders.
For further details

Pemphigus & Pemphigoid: From the Bench to the Bedside
Date: 5-6 November 2010
Venue: Bethesda, Maryland, USA

The meeting will bring together physicians and scientists interested in these diseases to meet face-to-face and facilitate interactions. The goal is to identify areas of research opportunity that will promote understanding of the causes and provide experimental and clinical justification for novel treatments of pemphigus and pemphigoid.
For further details

11th EPPOSI Workshop on Rare Disease Therapy Development Workshop
Date: 29-30 November 2010
Venue: Prague, Czech Republic

The topics of this year’s European Platform for Patients’ Organizations, Science and Industry workshop will include: Science - the determinants of rare disease research in Europe: understanding the current and future European Research and Development challenges and opportunities; Regulation - Europe and beyond: developing future regulations and policies for better rare disease therapies; and Sustainable Access - the reality we face to improve access to and affordability of orphan drugs.
For further details

4th International Meeting on the Congenital Disorders of Glycosylation and Related Disorders
Date: 13-14 January 2011
Venue: Leuven, Belgium

The meeting will cover all aspects of these disorders, including the discovery of novel types, the study of fundamental aspects of glycosylation, analytical procedures and diagnostic methods and the analysis of models for the disease. The meeting is organised by EUROGLYCANET, a European network for the advancement of research, diagnosis and treatment of a growing group of rare disorders. Deadline for abstract submission: 30 September 2010.
For further details

VII International Conference on Rare Diseases and Orphan Drugs (ICORD 2011)
Date: 21-23 May 2011
Venue: Tokyo, Japan

A global meeting on international cooperation and public health policies focussing on research, diagnosis, development of and access to treatment and care for rare diseases. The programme for this conference will be available shortly.
For further details

Eighth European Cytogenetics Conference
Date: 2-5 July 2011
Venue: Porto, Portugal

This meeting will provide the participants with an opportunity for not only contributing their knowledge and experience, but also for interacting with each other. Deadline for abstract submission: 28 February 2011.
For further details


Press & Publications
Summer reading suggestions for those still prowling the shelves (or the Internet) for the perfect rare disease beach book…
OrphaNews Europe has several suggestions for those who like to catch up on their rare disease reading during the summer months…

Title: Genetics of Mental Retardation: An Overview Encompassing Learning Disability and Intellectual Disability
Author: Knight, S.J.L –Ed.
Publisher: Karger, 2010
ISBN: 978-3-8055-9280-2

This work focuses on the importance of genetics in intellectual deficit, investigating the extent to which molecular diagnostic capability and the understanding of genetic causes have improved over recent years. In a single volume, a unique combination of key individuals and world-class clinical, diagnostic and research-based experts share specialised, state-of the-art knowledge. The parents’ perspective lies behind chapters dealing with issues such as: classification nomenclature; well-known syndromes; how modern technologies have resulted in newly identified syndromes; how genome architecture can influence disease; guidelines for clinical evaluation; valuable database resources for clinical, diagnostic and research departments; and more.

Title: Noonan Syndrome and Related Disorders - A Matter of Deregulated Ras Signaling
Author: Zenker, M. –Ed.
Publisher: Karger, 2009
ISBN: 978-3-8055-8653-5

In this book, internationally recognised experts review the most important advances regarding the group of human developmental disorders caused by constitutive dysregulation of the Ras-MAPK signalling pathway, including Noonan, cardiofaciocutaneous, LEOPARD and Costello syndromes.

Title: Tuberous Sclerosis Complex: Genes, Clinical Features and Therapeutics
Author: Kwiatkowski D.J., Holets Whittemore, V., Thiele, E.A. -Eds
Publisher: Wiley-Blackwell, 2010
ISBN: 978-3-527-32201-5

This book provides a comprehensive overview of the molecular basis and clinical features of the genetic disorder tuberous sclerosis. Special focus is placed on novel insights into the signal transduction pathways affected by the disease and genotype phenotype correlations. Existing and potential therapies are also discussed in depth. The editors are leading experts in research and treatment of the disease.

Title: Guide to Paediatric Drug Development and Clinical Research
Authors: Rose, K., van den Anker, J.N. –Eds.
Publisher: Karger, 2010
ISBN: 978-3-8055-9362-5

This book offers an overview of the worldwide activities that increasingly include children in the development of new medicines. Triggered by both a better understanding of how the child’s body develops as well as recent legislation in the USA and in Europe, this comprises dosing, ethics, age-appropriate pharmaceutical forms and clinical trials, amongst other aspects. A wide spectrum of readers can profit from this book, including paediatricians, pharmacists, general practitioners and health care professionals involved in child care and paediatric research, clinical trial personnel, patient advocacy groups, ethics committees, politicians, parents and interested lay persons.

For those readers interested in brushing up their French skills while staying current on rare disease issues, the Presse Médicale has produced a supplementary issue entirely devoted to the contributions of specialists participating in the rare disease colloquium held in Montpelier, France last October. An array of leaders weigh in on the topics of R&D, public-private collaborations, regulatory assessment, the French rare disease plan, the role of the patient organisation, registries, diagnostics, centres of reference, emerging technologies, medical devices for rare diseases, biobanks, and the ever-thorny issue of financing. With the exchanges between participants faithfully recorded, this special issue provides some très intéressant reading.

Finally, a new journal is offering free access to articles from its debut issue. Molecular Syndromology features “research articles, short reports and reviews on common and rare genetic syndromes, aiming to increase clinical understanding through molecular insights. Topics of particular interest are the molecular basis of genetic syndromes, genotype-phenotype correlation, natural history, strategies in disease management and novel therapeutic approaches based on molecular findings”.

Happy reading from the staff of OrphaNews Europe!


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
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Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Raphaël Demonchy, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Paloma Tejada, Aurélie Vandeputte
National Contact Point: Till Voigtländer (Austria), 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)
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