13 February 2008 print
Nat Pol News
Orphanet News
New Syndromes
New Genes
Research in Action
Patient Man & Therapy
Orphan Drugs
Courses & Education
What's on?
Press & Publications
Subscribe / Unsubscribe

The First European Rare Disease Day is only two weeks away...
Associations all over Europe are gearing up for the very first European Rare Disease Day, taking place on 29 February. A Rare Disease Day website, created by Eurordis and national rare disease alliances and patient groups, has been developed and lists the bonanza of activities taking place across Europe.

Here are just some of the events being planned to mark 29 February throughout Europe and beyond: Belgium is preparing a conference to be held at the national parliament. The country's new alliance of patient groups, Rare Disease Organisation Belgium, will officially launch on this day. Bulgaria is organising an open celebration in Sofia as well as a press conference; Denmark has a conference of professionals and patient organisations planned, an award ceremony for an individual or organisation's contribution to supporting rare diseases, and a march scheduled to take place in Copenhagen; France will hold a press conference and issue a press release. France-based Orphanet, the European portal of information on rare diseases and orphan drugs, is coinciding the release of its updated super user-friendly website on the 29th. Rich with information, this site is as much for the public as it is for professionals. Finland has strategically been promoting awareness for rare diseases and for the special rare disease day since the beginning of the month; Germany is launching a rare disease school project in Berlin, sensitizing its young citizens to the concerns of rare disease patients; Greece will run a television campaign the entire week leading up to 29 February, hold a press conference at the ministry of health and social affairs, and announce the winners of a country-wide school writing competition on "rare diseases"; Hungary is planning a conference and exhibition to be officially opened by the country's first lady; Information booklets are being prepared for the event. In Ireland, the Genetic and Rare Disorders Organisation is organising events in conjunction with the Medical Research Charities Group, Rehab Ireland, and the Irish Platform for Patient Organisations Science and Industry. Italy will raise awareness via press conferences, a cartoon for children, and a musical concert in Rome to which health authorities are invited. Luxembourg has created special pins featuring the rare disease day logo.

The Netherlands will have a gathering bringing together stakeholders from all over the country; Portugal has a national campaign underway to increase awareness. A press conference and public debate are also being planned; Romania is launching an awareness campaign with leaflets and posters being distributed and a special rare disease caravan. Informational seminars will be held in eleven major cities (those with medical universities); Spain will officially turn in to government a petition with some 25,000 signatures supporting the national rare disease plan. Media events include the release of 1000 balloons; Sweden will simultaneously celebrate the tenth anniversary of its national alliance. Activities include workshops and a special dinner; the Ukraine will hold a press conference and a film on the daily lives of children with rare diseases will be shown on national television; the United Kingdom will host a programme of evening receptions throughout the land and will involve government members. Across the ocean, Canada is on board with an eight-page supplement planned for publication in national newspapers and a crop of other actions - including a request to extend Rare Disease Day to Canada.

Finally, a Public Hearing is scheduled to follow up on the momentum of the European Rare Disease Day. Taking place on 4 March at the European Parliament in Brussels, this meeting will review the initiatives taking place throughout Europe and will also take a preliminary look at the results of the Public Consultation of the Commission Commmunication on European Action in the Field of Rare Diseases.

National & International Policy Developments
Romanian rare disease plan presented to Ministry
Romanian stakeholders finalised their national rare disease plan and presented it to the Ministries of Health and Education at the end of 2007. The plan, developed via a Romanian Prader Willi Association project in collaboration with the country's National Alliance for Rare Diseases, contains an ambitious set of objectives to help the estimated one million rare disease patients and their families living in Romania. These goals include improving access to information; establishing an adequate strategy for ensuring prevention, diagnosis, treatment and rehabilitation services; creating a national registry; stimulating research; creating rare disease training initiatives for professionals from various fields; and collaborating with various EU and international organisations. To develop a concrete plan of action, a methodology was created that involved identifying needs, creating work and expert groups, engaging ministry and institutions, arranging public debate and integrating the results, and disseminating the outcome of these efforts. A first action has been the creation of the National Committee of People with Rare Diseases, involving the Ministries of Health, Education, and Labour, as well as the National Medicine Agency, the Authority of People with Disabilities and the Child Welfare Authority. The activities of this committee include government decisions for coordination, guidance and control of services for rare disease patients, including social integration. The Romanian Prader Willi Association hopes to reach a signed agreement for their national plan on 29 February – Europe’s first Rare Disease Day.
Other European news
EUROCAT creates newsletter to communicate increasing information on congenital anomalies
The European Surveillance of Congenital Anomalies (EUROCAT) is a network of 41 population-based registries from 20 European countries that surveys over 1.5 million births per year. Created in 1979, EUROCAT today is able to monitor more than 25% of EU births. Information is lodged in a standardised database that contains more than 400,000 anonymised cases of congenital anomaly from throughout Europe. Now, to further enhance communication, EUROCAT has developed a newsletter that will provide news and information concerning the prevalence, risk factors, prevention and screening for congenital disorders. There are over 100,000 babies born with major congenital anomalies each year in the EU.

The decision to create a newsletter at this point in time evolves from the growing amount of information that EUROCAT is able to capture from a number of sources throughout Europe. This includes an increased availability of extensive prevalence data; new data on prenatal diagnosis that supplements existing information on pregnancy termination for foetal anomaly; surveys that EUROCAT conducts regularly of national policy and practice concerning issues such as folic acid supplementation or prenatal screening; and a major initiative to use the EUROCAT database for pharmacovigilance that is expected to yield some pertinent publications. EUROCAT is also working towards a series of publications regarding the epidemiology of genetic syndromes diagnosed prenatally or in the first year of life and is engaging in initiatives to further foetal health impact assessment in relation to environmental pollutants. The new EUROCAT newsletter will be published twice yearly.
Subscribe to the EUROCAT newsletter

Other International News
Increasing awareness for lysosomal storage diseases in Morocco
The patient organisation Espoir Vaincre les Maladies Lysosomales au Maroc was created last year by parents of youngsters suffering from hereditary metabolic disorders, with the support of the Biochemistry Laboratory and Hereditary Metabolic Disease Centre of the Rabat Children’s Hospital. Trying to bring together families that are currently isolated so they can share their experiences on accessing resources and improving the quality of daily life is the global goal of the group. They are also working to improve access to treatments that are currently expensive and difficult to attain in Morocco, as well as raising public awareness and generating support for psychosocial intervention and research. The association just held its second general assembly meeting during which the structure of the group was defined. A medical counsel, consisting of Moroccan and French medical and scientific experts, contributes on a voluntary basis toward meeting the organisation’s objectives. Espoir Vaincre les Maladies Lysosomales au Maroc is organising the first national information and awareness day for lysosomal storage diseases in Morocco, scheduled to take place in May. An estimated 120 patients have been identified to date in the country. The group does not yet have a website, but those seeking more information can contact Benyounès D’Hichi, general secretary of the group.

Orphanet News
New Texts
New Orphanet Journal of Rare Diseases publications
Primary Biliary Cirrhosis
Smith–Magenis Syndrome (published in the European Journal of Human Genetics, in association with Orphanet)


New Syndromes
8p23.1 duplication syndrome: facial dysmorphology, adrenal insufficiency, tetralogy of Fallot, cleft palate and syndactyly
The authors describe five patients; a de novo prenatal case and two families in which 8p23.1 duplications have been directly transmitted from mothers to children. All present a prominent forehead and arched eyebrows. Other symptoms vary and include adrenal insufficiency, tetralogy of Fallot, cleft palate and syndactyly.
Read the PubMed abstract

Eur J Human Genetics ; 18-27 ; January 2008
Autism with port-wine stain: a new syndrome
Over 15 years, four children presenting with unilateral facial port-wine stains and developmental disorders characteristic of autism (language delay, disturbed social interaction) were treated by the authors. Sturge-Weber syndrome was initially diagnosed, despite the absence of leptomeningeal angioma, a typical characteristic of the disease. Results from detailed neuropsychologic testing and positron emission tomography scanning of cerebral glucose metabolism lead the authors to propose a new clinical entity distinct from Sturge-Weber syndrome and infantile autism.
Read the PubMed abstract

Pediatr Neurol ; 192-199 ; September 2007

New Genes
HANAC syndrome has procollagen type IV alpha1 mutations
In 2005 a French team described a family with a new autosomal dominant syndrome characterised by hematuria, nephropathy, intracranial aneurysm and muscle cramps. In this study, the authors extend their study to two other families and identify mutations in the gene encoding procollagen type IV alpha1. They propose naming this syndrome: HANAC for Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps.
Read the PubMed abstract

NEJM ; 2687-2695 ; December 2007
Cutis laxa type II and wrinkly skin syndrome: function loss in the a2 subunit of the proton pump
The authors have identified mutations in the a2 subunit of the proton pump in patients with cutis laxa type II or wrinkly skin syndrome. Beside the wrinkled skin characteristic of these diseases, patients also present abnormal glycosylation of serum proteins.
Read the PubMed abstract

Nature Genetics ; 32-34 ; January 2008
Carney-Stratakis syndrome: three succinate dehydrogenase sub-units may have mutations
Carney-Stratakis syndrome is a recently described familial syndrome characterised by gastrointestinal stromal tumors and paragangliomas, often at multiple sites. The authors demonstrate the role of mutations in the genes encoding B, C, or D subunits of succinate dehydrogenase in this disorder.
Read the PubMed abstract

Eur J Human Genetics ; 79-88 ; January 2008
Alpha-cardiac actin mutations produce atrial septal defects
The authors have identified the gene-encoding alpha-cardiac actin, essential for cardiac contraction, as the likely candidate causing Interauricular communication type ostium secundum.
Read the PubMed abstract

Hum Mol Genetics ; 256-265 ; January 2008
Spinocerebellar ataxia type 16: a partial deletion of gene ITPR1
Spinocerebellar ataxia type 15 is a pure ataxia that can be attributed to partial deletions in gene ITPR1 (inositol 1, 4, 5-triphosphate receptor gene). The authors show in this study that spinocerebellar ataxia type 16 may also be due to a deletion in this gene.
Read the PubMed abstract

J Med Genetics ; 32-35 ; January 2008

Research in Action
Fundamental Research
Langerhans cell histiocytosis: high serum IL-17A levels are observed during active histiocytosis
Langerhans cell histiocytosis refers to the oligoclonal proliferation of Langerhans cells that occurs in children and young adults. Clinical presentation is variable, ranging from a single location in the bone to severe multivisceral involvement (i.e lungs, bone marrow, liver, spleen) leading to dysfunction of vital organs. In a mouse model of the disease, the authors examined whether the regulation of cytokine IL-17A has a positive effect not only on granuloma formation and neurodegeneration through unknown mechanisms, but also on bone resorption. They observed high serum levels of IL-17A during active histiocytosis and unexpected IL-17A synthesis by dendritic cells. Thus, the authors propose IL-17A as a possible therapeutic target for treating Langerhans cell histiocytosis.
Read the PubMed abstract

Nature Medicine ; 81-87 ; January 2008
Fragile X syndrome: a glutamate receptor contributes to the pathogenesis of the disease
Fragile X syndrome is the most common form of heritable mental retardation and the leading identified cause of autism. The syndrome is caused by transcriptional silencing of the FMR1 gene that encodes the fragile X mental retardation protein (FMRP), but the pathogenesis of the disease is unknown. One hypothesis explaining the neurological symptoms is the unchecked activation of mGluR5, a metabotropic glutamate receptor. To test this idea the authors generated Fmr1 mutant mice with a 50% reduction in mGluR5 expression and studied a range of phenotypes with relevance to the human disorder. The results demonstrate that mGluR5 contributes significantly to the pathogenesis of the disease.
Read the PubMed abstract

Neuron ; 955-962 ; December 2007
Trisomy 21: the risk of intestinal tumours is reduced in mice
Diverse epidemiological studies over the past 50 years present conflicting views as to whether there exists a lower incidence of solid tumours in trisomy 21 patients. The authors used mouse models of Down syndrome and of cancer in a biological approach to demonstrate the relationship between trisomy and the incidence of intestinal tumours. They found trisomy for orthologues of 33 of these genes in Ts1Rhr mice resulted in a significant reduction in the number of intestinal tumours. Further studies demonstrated that the Ets2 gene contributed most of the dosage-sensitive effect on intestinal tumour number.
Read the PubMed abstract

Nature ; 73-75 ; January 2008
Steinert muscular dystrophy: RNA toxicity induces NKX2-5 expression
Steinert muscular dystrophy is an autosomal dominant neuromuscular disease caused by the expansion of trinucleotides in an untranslated region of gene DMPK. Different studies suggest that mutated RNA is responsible for cellular toxicity implicated in different aspects of the phenotype. Using mutated RNA mouse models, the authors demonstrate that the dystrophic phenotype is linked to an increased expression of NKX2-5, a cardiac transcription factor. This study confirms RNA toxicity in the cardiac tissue and identifies the first genetic modifier of dystrophy in the heart.
Read the PubMed abstract

Nature Genetics ; 61-68 ; January 2008
Clinical Research
Mitochondrial DNA depletion syndrome: Twinkle helicase mutation phenotype extended to hepatocerebral forms of the disease
Mitochondrial DNA (mtDNA) depletion syndrome is a clinically and genetically heterogeneous group of autosomal recessive diseases characterised by a reduction in mtDNA copy number. Several nuclear genes have been shown to account for these severe oxidative phosphorylation disorders, but the disease-causing mutations remain largely unknown. Although dominant Twinkle mutations have been previously reported in patients with autosomal dominant progressive external ophthalmoplegia and multiple mtDNA deletions, the authors report the first recessive Twinkle mutation in patients with hepatocerebral form of the disease.
Read the PubMed abstract

Ann Neurol ; 579-587 ; December 2007
Malformations of the brainstem: a developmental classification
Using a retrospective study of 138 patients, the authors established a classification of brainstem anomalies, organising them into groupings based on known genetics and embryological events. The malformations were divided into four groups: (1) malformations with abnormal brainstem segmentation, (2) malformations with segmental hypoplasia, (3) postsegmentation malformations, and (4) malformations associated with abnormal cortical organisation.
Read the PubMed abstract

Ann Neurol ; 625-639 ; December 2007
Dominant optic atrophy: phenotypes associated with OPA1 mutations widen to include progressive external ophthalmoplegia
Mutations in gene OPA1, encoding a dynamin GTPase are the most frequent cause of autosomal dominant optic atrophy. The authors demonstrate that a mutation in this gene can lead to a wider phenotype, including visual failure and optic atrophy in childhood, followed by progressive external ophthalmoplegia, ataxia, deafness and a sensory-motor neuropathy in adult life. The mutation identified causes mitochondrial DNA depletion in the skeletal muscles and a deficiency of cytochrome c oxydase.
Read the PubMed abstract

Brain ; Epub ahead of print ; December 2007
Centronuclear myopathy: dynamin 2 mutations extend to severe neonatal forms of the illness
Centronuclear myopathies are heterogeneous neuromuscular diseases. Mutations in the gene encoding dynamin 2 are responsible for a late-onset autosomal dominant intermediary form of the disease. Now the authors of this study identify four new mutations in five patients presenting a more severe phenotype appearing in the first days or months of life.
Read the PubMed abstract

Ann Neurol ; 666-670 ; December 2007
Leukocyte adhesion deficiency type-1: reversion mutations in CD18 occur often
Leukocyte adhesion deficiency type-1 (LAD-1) is an autosomal recessive immunodeficiency caused by mutations in the beta2 integrin CD18 that impair CD11/CD18 heterodimer surface expression and/or function. The authors identified three cases of somatic reversion of CD18 mutations. All were observed at the same centre, suggesting that this type of event may occur relatively often in this pathology.
Read the PubMed abstract

Blood ; 209-218 ; January 2008
Cutis laxa and glycosylation disorder: apolipoprotein C-III isoelectric focusing is a diagnostic marker
The authors report on ten patients with autosomal recessive cutis laxa in combination with congenital disorder of glycosylation type II. The patients have a complex phenotype of neonatal cutis laxa, transient feeding intolerance, late closure of the fontanel, characteristic facial features including down-slanting palpebral fissures, short nose and small mouth, and developmental delay. While biochemical analysis using transferrin isoelectric focusing gives false negative results in some of the youngest patients, analysis of the apolipoprotein C-III isoelectric focusing is diagnostic in all cases.
Read the PubMed abstract

Eur J Human Genetics ; 28-35 ; January 2008
Trisomy 21 patients have few infantile hemangioma and lymphatic malformations
Epidemiological studies suggest that patients with trisomy 21 have a reduced risk of developing solid tumours (see the abstract in the fundamental research section of this newsletter). This new study shows that patients also have a reduced risk of developing infantile hemangioma and lymphatic malformations. The Children's Hospital Boston Vascular Anomalies Center database was searched in addition to the records of patients with Down syndrome treated at Children's Hospital Boston and the National Birth Defects Center, which were reviewed to find concurrent vascular anomalies. According to the authors, the trisomy leads to an elevated expression of antiangiogenic proteins that may protect these patients from developing vascular anomalies as well as solid tumours.
Read the PubMed abstract

Pediatrics ; e135-e140 ; January 2008
Stem Cells
Facioscapulohumeral muscular dystrophy: Mesoangioblasts could be candidates for autologous cell transplantation
Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited muscle disease. Because in FSHD patients the coexistence of affected and unaffected muscles is common, myoblasts expanded from unaffected FSHD muscles have been proposed as suitable tools for autologous cell transplantation. Mesoangioblasts are a new class of adult stem cells of mesodermal origin, potentially useful for the treatment of primitive myopathies of different etiology. In this study, the authors demonstrate that mesoangioblasts can be efficiently isolated from FSHD muscle biopsies and expanded to an amount of cells necessary to transplant into an adult patient. This could open the way to cell therapy for FSHD patients to limit muscle damage in vivo through the use of autologous mesoangioblasts capable of reaching damaged muscles and engrafting into them, without requiring immune suppression.
Read the PubMed abstract

Stem Cells ; 3173-3182 ; December 2007
Sickle cell anaemia: autologous cell transplantation derived from adult mouse skin
It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell-like state by introducing combinations of four transcription factors. However, the therapeutic potential of such induced pluripotent stem (iPS) cells remained undefined. By using a humanized sickle cell anemia mouse model, the authors show that mice can be rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy.
Read the PubMed abstract

Science ; 1920-1923 ; December 2007
Therapeutic Approaches
G(M1) gangliosidosis: a beta-galactosidase substrate analog improves mouse model phenotype
G(M1)-gangliosidosis is a neurodegenerative disease characterised by an accumulation of ganglioside G(M1). It is caused by a deficit of lysosomal beta-galactosidase. The authors administered orally a substrate analog of the enzyme, chaperone compound N-octyl-4-epi-beta-valienamine, to mouse models of the disease. An increase in beta-galactosidase activity, a decrease in ganglioside G(M1), and the prevention of neurological deterioration was observed in the treated mice. The authors conclude that N-Octyl-4-epi-beta-valienamine will be useful for chemical chaperone therapy of human G(M1)-gangliosidosis.
Read the PubMed abstract

Ann Neurol ; 671-675 ; December 2007
Spinal muscular atrophy: salbutamol increases SMN protein levels in vitro
Spinal muscular atrophy is an inherited neuromuscular disorder caused by homozygous absence of the survival motor neuron gene (SMN1). All patients have at least one, usually two to four, copies of the related SMN2 gene which, however, produce insufficient levels of functional SMN protein due to the exclusion of exon 7 in the majority of SMN2 transcripts. The authors of this study show that salbutamol, a beta2-adrenoceptor agonist, determines a rapid and significant increase in SMN protein in patient fibroblasts, predominantly by promoting exon 7 inclusion. The authors propose further research into the clinical efficacy of salbutamol in spinal atrophy patients.
Read the PubMed abstract

J Med Genetics ; 29-31 ; January 2008
Diagnostic Approaches
Hereditary non-polyposis colorectal cancer: Narrow band imaging improves adenoma detection
For patients with hereditary non-polyposis colorectal cancer, international recommendations advise coloscopic surveillance every one-to-two years from age 25. Although this reduces death rates, early interval cancers still occur, probably due to missed small, aggressive adenomas. The authors of this study show that use of narrow band imaging appears to improve adenoma detection, particularly those with a flat morphology, and could help reduce interval cancer rates.
Read the PubMed abstract

Gut ; 65-70 ; January 2008

Patient Management and Therapy
Strategies to advance translational research into brain barrier
There is a paucity of therapies for most neurological disorders, including rare lysosomal storage diseases. Delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by the blood-brain barrier, the blood-CSF barrier, or other specialised CNS barriers. These brain barriers are now recognised as a major obstacle to the treatment of most brain disorders. The challenge to deliver therapies to the CNS is formidable, and the solution will require concerted international efforts among academia, government, and industry. At a recent meeting of expert panels, essential and high-priority recommendations to propel brain barrier research forward in six topical areas were developed and these recommendations are presented in this article.
Read the PubMed abstract

Lancet Neurol ; 84-96 ; January 2008
Glioblastoma: new tools predict patient survival
Glioblastomas are malignant astrocytic tumours. The authors analysed data collected on 573 patients included in two different clinical trials. They then identified different criteria to be used as prognostic factors of survival. From these results, they developed nomograms that permit stratification of survival. These tools are available online.
Read the PubMed abstract

Lancet Oncol ; 29-38 ; January 2008
Familial hypercholesterolaemia: life and disability insurance consequences of screening
In the Netherlands, a national screening programme for familial hypercholesterolaemia has been in place since 1994. When a patient is identified, family members are contacted and genetic testing is proposed. Active identification by DNA testing has social implications such as difficulties in obtaining life and disability insurance. In The Netherlands, insurance companies are restricted by law in the use of genetic information of their clients. Within the scope of this specific law, a patient support association, representatives of the medical profession and insurers designed guidelines for risk assessment of mortality and morbidity of FH carriers. After implementation of these guidelines, the number of complaints concerning insurance contracts has decreased markedly.
Read the PubMed abstract

Eur J Hum Genetics ; 14-17 ; January 2008
Duchenne muscular dystrophy: an antisense oligonucleotide restores dystrophin expression in four patients
Duchenne muscular dystrophy is associated with severe, progressive muscle weakness. Antisense compounds were recently shown to restore dystrophin expression in vitro and in animal models in vivo. The authors of this study explored the safety, adverse-event profile, and local dystrophin-restoring effect of a single, intramuscular dose of an antisense oligonucleotide, PRO051, in patients with this disease. Intramuscular injection of PRO051 induced dystrophin synthesis in four patients who had suitable mutations, suggesting that further studies might be feasible.
Read the PubMed abstract

NEJM ; 2677-2686 ; December 2007
Dendritic cell sarcoma: An analytic overview of the literature and presentation of original five cases
Interdigitating and follicular dendritic cell sarcoma are very rare diseases, with approximately 184 cases being reported thus far. The authors present an analysis of these 184 cases that were described in the literature between 1981 and 2006. Radical surgery alone was curative in approximately two thirds of these cases, the relapsing rate in patients who received adjuvant treatments being higher than 30%. The authors suggest that localised dendritic cell sarcomas may be effectively treated by radical surgery and the evidence does not support the use of adjuvant treatments.
Read the PubMed abstract

Crit Rev Oncol Hematol ; 1-7 ; January 2008
Lysosomal storage disorders: progress with enzyme replacement therapy
In this article, the authors look at the use of enzyme replacement therapy for lysosomal storage diseases. They review the development, advances and limitations of these treatments.
Read the PubMed abstract

Drugs ; 2697-2716 ; 2007
Langerhans cell histiocytosis: a review of past, current and future therapies
The goal of therapy in Langerhans cell histiocytosis (LCH) is to decrease the activity and proliferation of histiocytes, lymphocytes and macrophages that cause the disease. Patients with disease that is localized to skin, bone and lymph node (defined as "nonrisk" organs) generally have a good prognosis and require minimal treatment. However, patients with lesions in "risk" organs (liver, spleen, lung, bone marrow) have a worse overall prognosis regarding mortality and morbidity. Likewise, patients with LCH in the central nervous system (CNS), vertebrae, facial bones or bones of the anterior or middle cranial fossa are at higher risk for morbidity and recurrent disease. LCH in the orbit, mastoid or temporal skull regions are classified as "CNS risk" because of an increased frequency of developing diabetes insipidus and other endocrine abnormalities or parenchymal brain lesions. The authors examine past and present clinical trials and therapeutic studies. Since LCH is a rare disease in children and adults, the authors suggest that these patients should be enrolled in clinical trials whenever possible to advance knowledge of the optimal therapeutic interventions and long-term outcomes.
Read the PubMed abstract

Drugs Today ; 627-643 ; September 2007

Orphan Drugs
Esteemed Prescrire award goes to rare disease product
French non-profit pharmaceutical industry review Prescrire recently bestowed its sought-after Pilule d’Or award to rare disease medical product Carbaglu (carglumic acid) marketed by Orphan Europe. Carbaglu permits children with congenital urea cycle disorder caused by N-acetylglutamate synthase deficiency to lead a normal life. Children born with this genetic disorder often die before diagnosis due to the severity and fast deterioration of clinical status. Carbaglu was granted marketing authorisation in Europe in 2003. The Pilule d’Or (or “Golden pill” in English) award is given to medicines that provide decisive therapeutic progress where there has previously been no treatment. Last year the review conferred its prestigious award to another orphan drug, Orfadin, used to treat hereditary tyrosinemia type 1, a rare paediatric disease causing progressive liver failure and liver cancer in young children.
First pharmaceutical gas approved in Australia is designated to treat rare condition
Ikaria Holdings Inc. announced marketing approval from Australian regulatory body Therapeutic Goods Administration for INOmax (nitric oxide), indicated for the treatment of newborns with hypoxic respiratory failure. According to a company press release, INOmax is the first pharmaceutical gas to receive approval in Australia. The product was designated an orphan drug in Australia. it has been available in Europe since 2001.
CHMP issues positive opinion for thalidomide in the treatment of multiple myeloma
The Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorisation for Thalidomide Pharmion (thalidomide) from Pharmion Ltd for the treatment of multiple myeloma. Thalidomide is the 45th orphan medicine to receive a positive opinion.
Negative opinion issued for lenalidomide
The CHMP adopted a negative opinion for Lenalidomide-Celgene Europe, from Celgene Europe, intended to treat anaemia due to myelodysplastic syndromes. A separate question-and-answer document explaining the rationale for the negative opinion is available on the EMEA website.

Courses & Educational Initiatives
Update in Neuromuscular Disorders
This course merges the latest research, clinical and management advances related to childhood neuromuscular disorders with adult inherited and acquired neuromuscular disorders and marks the inauguration of the new MRC Centre for Neuromuscular Diseases. Coursework includes Standards of care and latest research update in Duchenne MD; Anaesthetic management of muscular dystrophies; The floppy infant; Structural congenital myopathies; Spinal muscular atrophies: clinical aspects, functional scales, standards of care; Quality of life issues; Charcot Marie Tooth disease; Mitochondrial myopathies, and much more. From 16-20 June 2008 at the National Hospital for Neurology and Neurosurgery, London, UK.
For further details

Summer School at the Institute of Myology
The Institute of Myology offers a condensed 10-day course organised in Paris from 19-27 June 2008 and open to international students, with particular attention to those posted in the French Overseas Territories and working in developing countries. The major aspects of Myology are covered, including basic science, new therapies, and clinical and genetic approaches to muscle diseases via a series of lectures and interactive workshops in English.
For more information


What's on Where?
Third Eastern European Conference on Rare Diseases and Orphan Drugs
Date: 1-2 March 2008
Venue: Plovdiv, Bulgaria

Participants from Bulgaria and Eastern Europe will present their achievements in the field of prevention, diagnosis and treatment of rare diseases. A specialised workshop with speakers from leading US, European and Bulgarian organisations and institutions will take place in order to discuss best practices in the field of rare diseases and orphan drug access.
More details and to register

ACR Keystone Pediatric Rheumatology Symposium
Date: 1-5 March 2008
Venue: Colorado, US

The conference is intended to provide attendees with a forum to learn about and discuss the latest scientific advances in the subspecialty. Paediatric clinicians and researchers will benefit from the format that includes abstract sessions and study groups allowing casual interaction with speakers.
For further details

Rare Diseases: Channels and Transporters
Date: 8-12 March 2008
Venue: Sant Feliu de Guixols, Spain

The conference is devoted to channels and transporters involved in rare inherited diseases. Specifically TRP and CLC channels, connexins, mitochondrial transporters, heteromeric amino acid transporters, neurotransmitter transporters, ABC transporters and related diseases will be covered.
For further details

Second European Symposium on Rare Anaemias
Date: 13-14 March 2008
Venue: Nicosia, Cyprus

Sessions include current progress in prenatal and neonatal diagnosis of haemoglobinopathies, iron overload and chelation therapy, very rare anaemias, treatment of haemoglobinopathies, and red blood cell hereditary disorders.
For further details

Genomic Disorders 2008
Date: 17-20 March 2008
Venue: Cambridgeshire, UK

Topics to be discussed will include copy number variation and assays, structural variation predisposing to genomic rearrangement, mechanisms underlying genomic disorders, genomic rearrangements in common diseases and genetic syndromes, model organisms in the study of genomic disorders and potential therapeutic approaches.

For further details

Fifth International Congress on FMF and Systemic Autoinflammatory Diseases
Date: 4-8 April 2008
Venue: Rome, Italy

This conference will review current knowledge of the mechanisms of innate immunity and their relevance to the pathogenesis of autoinflammatory and other chronic diseases.
For further details

19th Conference of the German Society of Human Genetics
Date: 8-10 April 2008
Venue: Hannover, Germany

This year the main focus will be on the following subjects: Genetic origins of pain intensity, connective tissue disorders and complex infectious diseases; New therapeutic approaches to genetic diseases; The role of miRNAs and epigenetic modification; Proteomics; The structure of human genetic health care services in Europe.
For further details

International Ataxia-Telangiectasia Workshop 2008
Date: 22-26 April 2008
Venue: Kyoto, Japan

Topics include the roles of ATM and its related proteins in the DNA damage responses and in the tumorigenesis. The biological roles of ATM in the development of immune system, nervous system, and the stem cell systems are another essential area towards new therapies for A-T.
For further details

ICORD 4th International Conference on Rare Diseases and Orphan Drugs
Date: 20-22 May 2008
Venue: Washington, DC US
For further details

13th International Conference for Behçet's Disease and 5th Patients' Convention
Date: 24-27 May 2008
Venue: Klagenfurt, Austria

With presentations and discussions on oral, eye, genital and skin involvement, as well as paediatric patients, drug trials and future perspectives.
For further details

Myology 2008: Treatments – The Turning Point
Date: 29 May - 1 June 2008
Venue: Marseilles, France

Focusing on the development of therapies and the setting up of trials on humans for rare diseases in the field of myology.
For further details

First Conference on Translational Research in Paediatric Rheumatology
Date: 29 May - 1 June 2008
Venue: Genoa, Italy

Using the field of rare paediatric rheumatic disorders as a paradigm, Anticipating Changes in Drug Development for Children: Building on Paediatric Rheumatology will examine the medicine research and development process, from pre-clinical and early-phase clinical development, to biomarker validation, study design and management, data analysis, ethical review, regulatory submission and research governance. The conference is meant to further stimulate interaction among the three major stakeholders in the drug development process, namely, academia, industry and regulatory authorities.
For further details

5th International Congress of Rehabilitation in the Field of Neuromuscular Disorders
Date: 30 May – 1 June 2008
Venue: Marseilles, France

With sessions on gene-based therapies, patient evaluation, pain and fatigue management, and treatment options.
For further details

14th International Conference on Prenatal Diagnosis and Therapy
Date: 1-4 June 2008
Venue: Vancouver, Canada

Conference sessions will include foetal imaging, cytogenetics, foetal DNA/RNA, PGD, screening, teratology, and legal aspects of prenatal diagnostics and therapy. The deadline to submit an abstract for this conference is 4 February 2008.
For further details

Fourth International Neuroacanthocytosis Symposium: Bridging Clinical and Basic Aspects
Date: 1-2 July 2008
Venue: Oxford and London, England

Including clinical aspects of chorea acanthocytosis and McLeod syndrome, muscle and nerve neuropathology and syndromes related to NA.
For further details

Genetic Alliance Annual Conference 2008
Date: 11-13 July 2008
Venue: Bethesda, MD, US

Brings advocates, health professionals, policy makers, industry representatives, researchers, and community leaders together for workshops and discussions.
For further details

Fourth International Conference on Metals and Genetics
Date: 21-24 July 2008
Venue: Paris, France

The main topics will include metal-associated diseases: molecular and systemic biology approaches; characterisation and speciation of metal in proteins and biological tissues; and metals and environmental health implications.
For further details

Barth Syndrome: On Track Toward a Cure - 4th International Conference
Date: 21-26 July 2008
Venue: Florida, USA

This conference will be dedicated to increasing knowledge and accelerating advances in research for this rare metabolic genetic disorder. It will bring together basic scientists, clinical researchers, treating physicians, other professionals, and affected individuals and families to focus on the syndrome through a series of carefully organised sessions.
For further details

15th Paediatric Rheumatology European Society Congress
Date: 14-17 September 2008
Venue: University College London, UK

The programme will cover four main topics through keynote lectures, abstract presentations and educational workshops: juvenile arthritis, juvenile dermatomyositis, vasculitis and pain. There will be novel symposia such as sport and exercise in young people.
For further details

6th World Rett Syndrome Congress
Date: 10-13 October 2008
Venue: Paris, France

Various aspects of Rett syndrome and MECP2 functioning, including fundamental, clinical and management topics.
For further details

Tenth International Meeting on Osteogenesis Imperfecta
Date: 15-18 October 2008
Venue: Ghent, Belgium

Topics include: Bone homeostasis, murine models/collagen biology/biophysics, classification, genetics: genotype-phenotype, prenatal diagnosis/preimplantation diagnosis, biphosphonates, orthopedic management, hearing loss: physiopathology, surgery and imaging, other medical management issues, stomatology/dentistry, psychosocial aspects, new (therapeutic) perspectives.
For further details


Press & Publications
Two recent articles consider the orphan drug market in Europe...
One study determines the factors that favour orphan drug development in the EU
The authors of this study, published last month online in European Journal of Clinical Pharmacology, examine the various elements that facilitate the development of orphan drug products destined for sufferers of rare conditions. They found that “experience”, ie, a company that has already successfully brought an orphan drug to market, and “type of product” (synthetic versus biotechnology) are presently the most important predictors of authorisations of orphan drug products. A company with previous experience in this particular niche, particularly with a successful authorisation of an orphan drug, has a 16-fold increase in the chance of authorisation for another product versus a sponsor with no previous orphan drug authorisation. Existing synthetic molecules have a greater chance of reaching authorisation than either innovative synthetic or biotechnology entities. The authors suggest that more could be learned by studying the clinical development of orphan-designated products that do not receive marketing approval.
And another seeks to determine the number of products in the pipeline for ultra-rare conditions
Developing medicinal products for ultra-rare conditions is encouraged by current EU legislation. Yet justifying cost-effectiveness for individual country health systems can be an onerous process, (often referred to as the “fourth hurdle.”) The “rule of rescue” - defined as the imperative to save the lives of identifiable individuals when possible, despite potential high costs – has been employed to justify funding for certain products, but often conflicts with cost-effectiveness policy. With cost-effectiveness becoming an increasing priority as more new treatments become identified, this interesting survey of rare disease drug development, published in May 2007 in Oxford University Press review QJM, seeks to quantify the number of products currently in development for ultra-rare conditions. The study focuses on rare diseases with a prevalence of less than 1 in 50,000 and medicinal drug products in the phase II, III or pre-registration stage of development. One hundred and thirteen products were identified for forty-two rare conditions, with seventeen products in development for at least two indications. The authors propose that the potential high costs of new drugs for rare conditions could disproportionately impact health service budgets and call for ongoing debate to determine policy in this arena.

Orphanews Europe, the newsletter of the Rare Diseases Task Force
Orphanews Europe is supported by the European Commission's DG SANCO
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Catherine Berens, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
For more information on the Rare Diseases Task Force
Orphanet - All rights reserved