26 January 2011 print
Spotlight on...
EU Policy News
Nat Pol News
ELS News
New Syndromes
New Genes
Research in Action
Patient Man & Therapy
Orphan Drugs
Partnersearch, Job Opps
Courses & Education
What's on?
Subscribe / Unsubscribe

East meets West as the sun rises higher for rare disease patients in Japan

In mid-January, stakeholders from Japan’s Health Ministry, National Institute of Public Health, and academia, met in Tokyo with Ségolène Aymé, director of Orphanet, the pan-European rare disease and orphan drug information and reference portal, and current Chair of the European Union Committee of Experts on Rare Diseases (EUCERD). The encounter is part of Japan's ongoing explorations of how to optimise resources for rare diseases, and follows a visit in 2009 to relevant stakeholders in the USA, and a tour of European countries in October 2010 – including a visit to the Orphanet offices in Paris, France, as well as meetings with other rare disease stakeholders in Belgium, Denmark, France, Sweden and the United Kingdom. The weeklong exchange in Japan with Ségolène Aymé allowed for rich discussions on both the Japanese and European perspectives of how to best serve the various and often complex needs of rare disease patients. In attendance were Dr. Yoshio Namba, Director of the Specific Disease Division, Ministry of Health, Labour and Welfare; Kenji Hayashi, MD, President of the National Institute of Public Health; Tomoko Kodama, MD, Project Officer of the Rare and Intractable Diseases Project; Ichiro Kanazawa, MD, the Chair of the Committee on Rare/Intractable diseases (Nanbyo) at the Ministry of Health, Labour and Welfare and Medical Supervisor for Royal Families, Imperial Household Agency; and Yasuo Itoyama, MD, Director General of the National Center of Neurology and Psychiatry.

Japan bears the distinction of having the oldest programme for rare disease research and care in the world. Established in 1972, the Medical Care Program for Specific Diseases encompasses “Nanbyo” (Intractable Diseases) and the closely-related “Tokutei Shikkan” (Specified Rare and Intractable Diseases). The word “Nanbyo” can be understood by its two syllables: “Nan” meaning something difficult or worrying; and “Byo” being the Japanese word for “disease”. Japan’s Nanbyo programme can thus include any troubling, untreated disorder, though the vast majority of conditions it accepts – determined by a consultative committee - are rare. While historically infectious diseases such as cholera or tuberculosis were considered Nanbyo, today the intractable diseases are defined as those “…that have resulted from an unidentifiable cause and, without a clearly established treatment, have a considerably high risk of disability” and “…that chronically develop and require a significant amount of labor for the patient’s care, causing a heavy burden on other family members of the patient, both financially and mentally”. Requests for inclusion can come from medical professionals as well as the patient organisations. Diseases taken up under the programme receive funding for research and allow patients full health coverage. Currently, of the 130 disease groups covered under the Nanbyo programme for clinical research, 56 diseases in the Tokutei Shikkan programme receive specific subsidiaries from public funding, include Behcet disease, pemphigus, the lysosomal storage diseases, retinitis pigmentosa, and acromegaly. Some 650,000 patients benefit from medical expense support in Japan. Learn more

No man is an island…
Many countries that have formerly operated autonomous research and health programmes can no longer afford to do so in face of the enormous financial and resource challenges the rare diseases impose. Japan is one of many countries exploring cooperative strategies and initiatives for better managing rare diseases and orphan drugs. The European Council Recommendation on an action in the field of rare diseases and the successful termination of the first term of the French rare disease plan – considered a model - is inspiring other countries around the world. Coupled with the expanding development of medicinal products for rare diseases contributing to rising costs for countries’ health systems, Japan, like other nations, is trying to streamline expenses. Japan, which has been insular in its research and drug programmes for rare diseases, recognises the advantage of global collaboration and cooperation, particularly in the field of research. Steps forward include negotiations toward a partnership with rare disease and orphan drug information portal Orphanet – which would allow for Japanese translation of the site’s database of information on rare diseases and orphan drugs, and enable information on Japanese resources to be added. Another forward movement is Japan’s possible participation in an upcoming meeting between stakeholders from US and European rare disease research programmes (learn more). Also, the European Union Committee of Experts on Rare Diseases (EUCERD) is planning to invite Japan to join as an observer.

These are exciting times for rare disease patients, researchers, and other stakeholders alike, as more and more countries bring their unique experiences, talents and perspectives to the table to work together on behalf of rare disease patients and their families in all countries.

Spotlight on...
the International Network of Paediatric Surveillance Units (INoPSU)
Richard Lynn, INoPSU Liaison Officer and Scientific Coordinator for the British Paediatric Surveillance Unit

The British Paediatric Surveillance Unit (BPSU) has been facilitating epidemiological surveillance into rare paediatric conditions for over 20 years, including research into more than 70 rare paediatric diseases, the results of which have had a major impact on child health policy in the UK.

The methodology has been so successful that it has been adopted by other medical specialties within the UK and in paediatrics in a dozen countries around the world. In 1998 a network was formed, called the International Network of Paediatric Surveillance Units (INoPSU). This network covers a child population of over 50 million children and 10,000 paediatricians. Between the various members, epidemiological surveillance of nearly 200 rare paediatric conditions has been effectuated.

OrphaNews Europe spoke with Richard Lynn, INOPSU Liaison Officer and Scientific Coordinator for the British Paediatric Surveillance Unit:

OrphaNews Europe : How was the International Network of Paediatric Surveillance Units (INoPSU) formed and for what purpose?

Richard Lynn : The British Paediatric Surveillance Unit has existed since 1986. Quickly thereafter, other countries such as Germany, the Netherlands and Switzerland developed an interest in collecting cross national data on vitamin k deficiency bleeding and Haemophilus b influenzae infections. The European initiative was the stimulus for the development of Australian, Malaysian and Canadian Paediatric Surveillance Units (PSUs). By the time of its launch in 1998, the International Network of Paediatric Surveillance Units (INoPSU) had 10 founding member countries covering a collective child population of over 48 million.

INoPSU's mission is to advance the knowledge of rare and uncommon childhood conditions that are high in disability, morbidity, mortality and economic cost to society, despite their low frequency, and to improve clinical practice and health policy by providing detailed epidemiological, clinical and outcomes data through surveillance on a national and international basis. INoPSU aims to enhance communication and collaboration between national PSUs and child health researchers worldwide by collecting simultaneous or sequential, standardised data to allow data comparison and to disseminate information on rare paediatric diseases to clinicians and the public alike. Our work on haemolytic uraemic syndrome and early onset eating disorders are two examples.

OrphaNews Europe : How many countries presently participate in the INoPSU? What is the relationship between national surveillance efforts and the INoPSU?

Richard Lynn : Currently there are 12 countries participating in the activities of INoPSU. Some countries (UK and Australia) have also extended active surveillance to several specialities other than paediatrics, such as ophthalmology, lung disease and psychiatry. The network communicates through its administrative centre based in the UK. The centre is kept informed of new studies under development. This allows for the sharing of study protocols and assists in connecting researchers in different countries working on simultaneous studies. In addition, the network shares publications of recent papers and other news and developments via email and through newsletters and the INoPSU website. Unit representatives and researchers come together every two years for a conference devoted to surveillance for rare paediatric conditions and to exchange information and discuss aspects of rare disease surveillance methodology and priority conditions for surveillance. The last such gathering was in Dublin Ireland last October where participants had the chance to hear Dr Ana Rath from Orphanet present on improving the quality of medical care for rare diseases.

OrphaNews Europe : How are diseases selected for inclusion in the INoPSU reports?

Richard Lynn : Conditions for surveillance are selected by the individual national PSUs according to national priorities and public health needs. Conditions are often chosen for surveillance when there are no other sources of information about the epidemiology and clinical management of rare conditions. INoPSU reports often focus on conditions that have been studied in more than one country to highlight international comparisons in addition to reporting data that have been collected by individual PSUs to inform public health responses to disease management and prevention in that country over the past year.

OrphaNews Europe : How many rare diseases have been surveyed and why have the specific rare diseases included for monitoring been chosen?

Richard Lynn : Over 200 different rare paediatric conditions have been surveyed by the 12 countries within INoPSU. Many of the conditions have been studied by more than one national PSU, such as HIV, hyperbilirubinaemia, haemolytic uraemic syndrome and congenital rubella syndrome.

Each national PSU has a multidisciplinary Steering Committee that oversees the programme and reviews new study proposals. The conditions are chosen based on inclusion criteria such as, rarity, public health and scientific importance, and uniqueness. Some studies arise out of interest from individual paediatricians within a country, or are chosen because of national health policy need, for example, those relating to screening, hyperbilirubinaemia or a disease outbreak such pandemic influenza and variant-CJD (Creutzfeldt-Jakob disease). Some conditions are put forward by researchers and clinicians with support from patient groups.

Read the full interview with Richard Lynn


EU Policy News
European Parliament votes in cross-border healthcare; EC Heath Commissioner John Dalli evokes benefits to rare disease patients

On 19 January, the European Parliament voted in favour of the EU Directive on Patients' Rights in Cross-border Healthcare. In a statement, John Dalli, European Commissioner for Health and Consumer Policy, stated that the Directive will “ … help patients who need specialised treatment, for example those who are seeking a diagnosis or treatment for a rare disease”. The law still needs the formal approval from the EU Member States before it can become operational. As was reported in the 20 October issue of OrphaNews Europe, the directive seeks to eliminate obstacles hindering patients from seeking treatment in another Member State and clarifies patient rights to reimbursement for treatment obtained abroad. However, the directive has no impact on the rights of each Member State to determine which health benefits they will provide. If a particular treatment is not reimbursed in a patient’s home country, it will not be reimbursed if accessed in another Member State. The directive, which has been amended several times, has had a provision added to strengthen the cooperation between MS through the development of European reference networks “which will bring together, on a voluntary basis, specialised centres in different Member States”. Such cooperation is particularly relevant in the field of rare diseases. While the directive is generally considered welcome, according to a news report in the EU Observer, criticism has been raised over potential discrimination for those EU citizens who are unable to pay “for procedures upfront and then wait to get reimbursed later back home”.
Consult the statement from John Dalli
Consult the European Parliament press release

European Network of Paediatric Research publishes membership list
The European Medicines Agency (EMA) has announced publication of the first membership list of the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA). Established to “build a high-level network of existing research networks, investigators and centres with recognised expertise in performing clinical studies in children,” the Enpr-EMA seeks to facilitate “high-quality ethical research on medicines for use in children through networking and stakeholder collaboration with members from both within and outside the European Union” as part of the EMA’s accordance with European Paediatric Regulation (EC) No 1901/2006. The majority of rare diseases affect paediatric populations. The Enpr-EMA membership list was compiled following a call for expressions of interest in 2010. Some 32 networks and centres have thus far applied for membership. Of these, 16 networks and centres have become members of Enpr-EMA. A second category of networks has been established for those “… undergoing clarification before membership of Enpr-EMA”. Networks grouped into a third category do not currently qualify for membership. Any networks, centres, or investigators interested in becoming members of Enpr-EMA are invited to complete the self-assessment form.
Consult the membership lists of the Enpr-EMA


National & International Policy Developments
Scientists take umbrage at German genetic diagnostics law
As was reported in the 19 March 2010 issue of OrphaNews Europe, the German Bundestag last year passed into effect the Genetic Diagnostics Act, which regulates the practice of testing on humans as well as the handling of samples and data but does not extend to testing and data/samples undertaken for research purposes. Less than a year later German scientists have issued a report and recommendations to try and make the law more compatible with actual practice. According to a news report on the GenomeDailyWeb, the group of experts from the Union of German Academies of Sciences Leopoldina finds the legislation “…in desperate need of amendment" and “…out of touch with the latest technology, almost impossible to implement in clinical practice, or even detrimental to the success of recognized screening tests". One example cited in the media concerns newborn screening, defined under the legislation as universal genetic screening. As such, parents must be informed prior to blood samples being taken, but only by a physician – not a nurse or midwife. Consequently, “there is increasing evidence that in the case of home births, blood samples are frequently not taken and screenings not conducted, even though this is not actually in line with the parents’ wishes”. An unofficial English-language translation of the Act can be found on the website of European Network of Excellence EuroGentest.
Consult the Leopoldina report (in German language)

Rare diseases and orphan drugs as models for personalised medicine framework
Scientific developments, particularly in the fields of the life sciences and genomics, are opening the door to “to move towards the development, use and reimbursement of targeted or ‘personalized’ therapies”. Furthermore, society seems to support this direction. A pertinent article appearing in the journal Personalized Medicine evokes many elements from the field of rare diseases and orphan drugs that are informative to the development of a framework for personalised healthcare. Such elements include registries, centres of excellence, patient group collaboration, industry collaboration, and the development of (expensive) products for small patient populations. These fixtures of the rare disease/orphan drug landscape readily lend themselves to the personalised healthcare framework. The common ground between rare diseases and personalised medicine exist “…mostly in that they both address unmet medical needs and combine diagnosis with therapy, that they both need a lot of communication and awareness-building, and that they both need the involvement of all stakeholders to optimize societal outcomes.” Thus, it is suggested that “…policy makers should be willing to create incentives and pathways for industry and society to succeed and should look at the field of rare diseases for inspiration and solutions. One of the most important models to be transferred from the field of rare diseases is the use of multistakeholder platforms to discuss the complex multifactorial issues associated with personalized healthcare.” Towards a Framework for Personalized Healthcare: Lessons Learned From the Field of Rare Diseases shows how the policies and practices that have been established in the field of rare diseases and orphan drugs can serve to streamline targeted medicine, ultimately making healthcare systems more efficient.
Consult the abstract

First colloquium of the Quebec Coalition of Orphan Diseases moves the ball forward for rare disease patients

The Regroupement Québécois de Maladies Orphelines RQMO (Quebec Coalition of Orphan Diseases) held its first colloquium in the presence of Health Minister Dr. Yves Bolduc, who gave the opening address. The audience, which consisted of stakeholders from many domains, including rare disease patient organisations, were rewarded by the announcement from the Health Minister that the orphan diseases would indeed be “adopted” by Quebec’s health system. Dr. Bolduc also agreed to a request to create a committee specifically dedicated to rare diseases. True to his word, since the colloquium took place in October, a mandate to create this body has been issued to Quebec’s Institut National d’Excellence en Santé et Services Sociaux. Other promising actions include a possible collaboration between the Quebec health system and rare disease and orphan drug information portal Orphanet. Learn more about the RQMO colloquium (in French language)

Other International News
Study points out inequity in prenatal screening in Western Australia
A new study reveals inequity in prenatal screening practice in Western Australia, “particularly for Aboriginal, remote and socio-economically disadvantaged women”. Linking prenatal screening data collected from accredited ultrasound and pathology laboratories in Western Australia to diagnostic and pregnancy outcome data, the authors were able to analyse the screening performance characteristics and uptake by socio-demographic characteristics for over 35,000 women and almost 60,000 related births. Aboriginal women had the lowest uptake of screening, followed by those living in remote areas, women under the age of 25, women in the lowest quintile of the socio-economic indexes, and those with three or more children. This study represents a first step in assuring more equitable prenatal screening uptake across Western Australia. Consult the abstract
New software helps clinicians making difficult diagnoses

Commercially-available software that originated in the area of neurological syndromes “matches physician-entered patient findings to diseases and uses a statistical pattern-matching technique to provide an immediate differential diagnosis”. SimulConsult (“Simultaneous Consult”) computes information from a database offering evidence-based characterisations for over 2500 genetic neurological and metabolic diseases. This database, which is expanding to encompass other disease groups, is “built by clinicians, referenced to the literature, reviewed by editors, and updated many times per month”. Physicians enter known clinical and laboratory findings for a specific case, including pertinent positives and negatives, along with the time course of individual findings, and SimulConsult provides a differential diagnosis as well as suggestions for other tests and possible findings that might further refine the diagnosis. Learn more


Ethical, Legal & Social Issues

Article revisits complex issue of deliberate growth restriction for severely disabled children
A thought-provoking article published in the Hastings Center Report revisits a case that caused profound controversy amongst medical professionals, ethical boards, and the general public. It involves a severely disabled, nonambulatory six-year-old girl who was administered estrogen to restrict her final height and also had her uterus and breast buds surgically removed (learn more). The interventions, labelled growth attenuation, were undertaken at Seattle Children’s Hospital at the request of the patient's family, who believed that the procedures would allow them to more easily lift, move and care for their daughter, permitting them to include her in more social and recreational activities, and allowing them to avoid institutionalisation. The paper, Navigating Growth Attenuation in Children with Profound Disabilities, presents the considerations gleaned from a twenty-person working group of health professionals, ethicists, experts in law, and parents of similarly affected children, who discussed many of the ethical and policy aspects of the intervention. While consensus was not attained, compromise was reached for many of the various topics considered, which include the devaluation of people with disabilities; concerns about misuse; identity and bodily integrity; dignity and respect; and certainty and permanence. According to the blog maintained by the parents of the child who underwent the growth attenuation, there are “about a dozen” families around the world who have had similar interventions performed on their severely disabled children. Consult the PubMed abstract

New Syndromes

Hemorrhagic destruction of the brain, subependymal calcifications and congenital cataracts: JAM3 involved
The authors describe an autosomal recessive syndrome affecting several members of a consanguineous family: patients suffer from severe hemorrhages of the brain, subependymal calcifications and congenital cataracts, a clinical presentation that partially overlaps with pseudo-TORCH syndrome, caused by the occludin mutation, a tight junctions protein. A causal mutation was identified in JAM3, another tight junctions protein.
Read the PubMed abstract

Am J Hum Genet ; 882-889 ; 10 December 2010
Autoimmunity, infections, hepatopathy, encephalopathy and cardiac malformations
The authors report the identification of a FADD mutation by a combination of genome-wide linkage and whole-exome sequencing in a consanguinous family of which several members suffer from an autoimmune lymphoproliferative syndrome in a context of bacterial and viral severe infections, recurrent hepatopathy and encephalopathy and cardiac malformations. The authors show that the mutation decreases the protein level of FADD which alters FAS-dependant apoptosis in vitro. Bacterial infection seems linked to a functional hyposplenism and viral infections are due to impaired interferon immunity.
Read the PubMed abstract

Am J Hum Genet ; 873-881 ; 10 December 2010
16q21 microdeletion: susceptibility to autism and learning disability linked to the CDH8 gene
The authors report a rare cause of susceptibility to autism and learning disability in two families with autism with and without learning disability. Affected patients harbour rare microdeletions in the 16q21 region disrupting only one gene, coding for cadherin 8.
Read the PubMed abstract

J Med Genet ; 48-54 ; January 2011

New Genes

Seckel syndrome: involvement of the centrosomal CEP152 protein in genomic integrity maintenance
Read the PubMed abstract
To read more about "Seckel syndrome"

Nat Genet ; 23-26 ; January 2011
Narcolepsy: common variants of the P2RY11 gene as susceptibility factors
Read the PubMed abstract
To read more about "Narcolepsy without cataplexy"

Nat Genet ; 66-71 ; January 2011
Primary sclerosing cholangitis: two non-HLA susceptibility loci identified
Read the PubMed abstract
To read more about "Primary sclerosing cholangitis"

Nat Genet ; 17-19 ; January 2011
Treacher-Collins syndrome: two RNA polymerases I and III subunits at cause
Read the PubMed abstract
To read more about "Treacher-Collins syndrome"

Nat Genet ; 20-22 ; January 2011
Dursun syndrome: G6PC3 is responsible for arterial hypertension, leukopenia and atrial septal defect
Read the PubMed abstract
To read more about "Pulmonary arterial hypertension - leukopenia - atrial septal defect"

Am J Med Genet ; 2609-2611 ; October 2010
CK syndrome: NSDHL gene mutations at cause
Read the PubMed abstract
Am J Hum Genet ; 905-914 ; 10 December 2010
Joint contractures, muscle atrophy, microcytic anemia and lipodystrophy: PSMB8 implicates the immunoproteasome
Read the PubMed abstract
Am J Hum Genet ; 866-872 ; 10 December 2010
Nemaline myopathy: dominant mutations of the KBTBD13 gene identified
Read the PubMed abstract
To read more about "Nemaline myopathy"

Am J Hum Genet ; 842-847 ; 10 December 2010
Kahrizi syndrome: frameshift mutation of SRD5A3 and disruption of protein glycosylation
Read the PubMed abstract
To read more about "Intellectual deficit, Kahrizi type"

Eur J Hum Genet ; 115-117 ; January 2011
Limb-girdle muscular dystrophy: the 1f isoform of PLC is involved in the autosomal recessive disease form
Read the PubMed abstract
To read more about "Limb-girdle muscular dystrophy"

Am J Hum Genet ; 834-841 ; 10 December 2010
Autosomal recessive cerebellar ataxia: mutations in ANO10, a putative chloride channel
Read the PubMed abstract
To read more about "Autosomal recessive cerebellar ataxia"

Am J Hum Genet ; 813-819 ; 10 December 2010
Pelizaeus-Merzbacher disease : AIMP1 at cause
Read the PubMed abstract
To read more about "Pelizaeus-Merzbacher disease"

Am J Hum Genet ; 820-828 ; 10 December 2010
46,XY disorder of sex development: involvement of the MAP3K1 kinase in the testicular development
Read the PubMed abstract
To read more about "46,XY disorder of sex development"

Am J Hum Genet ; 898-904 ; 10 December 2010

Research in Action

Fundamental Research
Amyotrophic lateral sclerosis: a strategy of mutated SOD1 stabilisation to reduce toxicity
Read the PubMed abstract
To read more about "Amyotrophic lateral sclerosis"

PNAS ; Epub ahead of print ; 22 November 2010
Fragile X-associated tremor/ataxia syndrome: histone acetylation as a therapeutic target
Read the PubMed abstract
To read more about "Fragile X-associated tremor/ataxia syndrome"

PLoS Genet ; e1001240 ; 9 December 2010
Duchenne muscular dystrophy: therapeutic potential of myogenic HLA-E expressing cells
Read the PubMed abstract
To read more about "Muscular dystrophy, Duchenne type"

Hum Mol Genet ; 235-244 ; 15 January 2011
Clinical Research
Chronic granulomatous disease: correlation between residual NADPH oxidase activity and disease severity
Read the PubMed abstract
To read more about "Chronic granulomatous disease"

N Engl J Med ; 2600-2610 ; 30 December 2010
Huntington disease: 12 month clinical follow up of mutant HTT carriers in premanifest and early disease stage
Read the PubMed abstract
To read more about "Huntington disease"

Lancet Neurol ; 31-42 ; January 2011
Acute myeloid leukemia: DNMT3A mutations associated with a poor prognostic
Read the PubMed abstract
To read more about "Acute myeloid leukemia"

N Engl J Med ; 2424-2433 ; 16 December 2010
Acute myeloid leukemia: risk assessment of intensive chemotherapy in patients over 60
Read the PubMed abstract
To read more about "Acute myeloid leukemia"

Lancet ; 2000-2008 ; 11 December 2010
Cystic fibrosis: genotype, phenotype severity and risk of pancreatitis
Read the PubMed abstract
To read more about "Cystic fibrosis"

Gastroenterology ; 153-161 ; January 2011
Cystic fibrosis: p.Sr1235Arg mutation is no longer pathogenic
Read the PubMed abstract
To read more about "Cystic fibrosis"

Eur J Hum Genet ; 36-42 ; January 2011
Ring chromosome 20: two causal molecular mechanisms for two phenotypic spectra
Read the PubMed abstract
To read more about "Ring chromosome 20"

J Med Genet ; 1-9 ; January 2011
Gene Therapy
Mucopolysaccharidosis type I: alpha-L-Iduronidase overexpression in transplanted hematopoietic stem cells
Mucopolysaccharidosis type I is caused by an enzymatic deficiency of alpha-L-iduronidase. Severe forms of the disease affect the brain and bones, both difficult to access via enzyme-replacement therapy or with hematopoietic stem cell (HSCs) transplantation. In this article, the authors report promising results obtained on a mouse model with the lentiviral-mediated overexpression of the alpha-L-iduronidase by the transplanted HSCs. The overexpression allows hematopoietic cells to deliver active enzymes to the brain and skeleton and to correct disease manifestations.
Read the PubMed abstract

To read more about "Mucopolysaccharidosis type 1"

Blood ; 5130-5139 ; 9 December 2010
Haemophilia A: eradication of neutralizing antibodies to factor VIII after liver gene therapy in the dog
Haemophilia A, caused by a factor VIII activity deficit, is managed with infusion of plasma-derived or recombinant factor VIII. These strategies are limited by the patient’s immune reaction that synthesises antibodies against the exogenous factor VIII. In order to limit the production of so-called neutralizing or inhibitory antibodies, an immune tolerance induction can be triggered through infusion of a massive dose of factor VIII during a long period. The authors report an alternative approach tested on the liver of dogs, based on the same tolerance induction principle, but using a factor VIII endogenous production mediated by an AAV vector carrying the factor VIII gene. After a single injection of the vector, the antibodies’ titration dropped in a few weeks, leading to a dramatic and durable rise of efficient factor VIII in the dogs' blood.
Read the PubMed abstract

To read more about "Hemophilia A"

Blood ; 5842-5848 ; 23 December 2010
Pompe disease: efficiency of isolated limb perfusion viral vector delivery in a mouse model
The authors propose a method of hydrostatic isolated limb perfusion in order to optimise the transduction efficiency of an AAV vector in the hind limb muscles of GAA-KO mice. Results show a clear advantage of this technique compared to a simple intravenous injection; the vector quantity needed being far less for an increased transduction rate. In addition, the authors report that muscular fibers type II have also been transduced with this technique, an interesting point as these fibers are resistant to enzyme replacement therapy.
Read the PubMed abstract

To read more about "Glycogen storage disease type 2"

Gene Ther ; 1500-1505 ; December 2010
Dystrophic epidermolysis bullosa: in vitro correction of the phenotype via a trans-splicing strategy
Dystrophic epidermolysis bullosa is caused by a defect in type VII collagen, frequently consecutive of premature termination codons. The authors exploited the capacity of cells to reconstitute a coding RNA from two distinct RNA molecules via the trans-splicing mechanism in order to avoid the transduction of a too large integral sequence of the COL7A1 gene: the retroviral vector contains a 3’ part of the gene and the transduced cells express a reconstituted version of the type VII collagen. Results obtained on patients’ primary culture cells are encouraging enough to foresee the development of this strategy in dystrophic epidermolysis bullosa.
Read the PubMed abstract

To read more about "Dystrophic epidermolysis bullosa"

J Invest Dermatol ; 74-83 ; January 2011
Therapeutic Approaches
Fanconi anaemia: partial improvement of the hematopoietic defect in a mouse model via resveratrol
Fanconi anaemia leads to a progressive bone marrow failure, an important cause of mortality and morbidity in patients. In this study, the authors show that the Fancd2-/- mouse model is well suited for pharmacological substances screening. They tested the efficiency of resveratrol, an antioxidant polyphenol found in grapes and red wine, and found a beneficial effect on mice hematopoietic failure.
Read the PubMed abstract

To read more about "Fanconi anemia"

Blood ; 5140-5148 ; 9 December 2010
Huntington disease: neuroprotective effect of fisetine and resveratrol in several experimental models
Neurodegeneration process leading to Huntington disease follows diverse cellular pathways among which are the MAP kinases and the ERK cascade. In this article, the authors highlight the beneficial effect of fisetine and resveratrol, two polyphenols able to specifically activate the ERK pathway in three experimental models of the disease (cell culture, drosophila and mouse).
Read the PubMed abstract

To read more about "Huntington disease"

Hum Mol Genet ; 261-270 ; 15 January 2011
Mantle cell lymphoma: therapeutic cooperation between two chemotherapeutics and a reprogrammed virus
The authors challenge the efficacy of a therapeutic approach combining two chemotherapeutics (fludarabine and cyclophosphamide) and the measles virus reprogrammed to selectively infect CD20-expressing cells and containing an enzyme able to activate the fludarabine and thought to potentiate its oncolytic effect. Results obtained on a mouse xenograft model show that three 23-day courses of triple sequential treatment with CPA (immunosuppression), virus (cancer cells infection) and FLU (cytotoxic activity) leads to a complete regression of xenografts and improves survival from 22 to 77 days. Though serious side effects interfered with mice survival, the authors suggest that treatment efficiency justifies a phase I clinical trial to be carried out with patients for whom conventional therapies have failed.
Read the PubMed abstract

To read more about "Mantle cell lymphoma"

Gene Ther ; 1506-1516 ; December 2010

Patient Management and Therapy

Chronic myeloid leukemia: advantage of the imatinib – peginterferon alfa-2a combination
Only a minority of chronic myeloid leukaemia patients have a complete molecular remission with the classical imatinib treatment (400 mg daily). In a multicentric phase 3 trial, the investigators assessed the efficiency of the imatinib – peginterferon alfa-2a combination. For this trial, 636 patients were randomly assigned to receive imatinib alone (400 mg/d), imatinib plus cytarabine or pegylated interferon alfa-2a, or imatinib alone at 600 mg/d. The results show a clear advantage for the association of imatinib and interferon, with a significantly higher molecular response rate.
Read the PubMed abstract

To read more about "Chronic myeloid leukemia"

N Engl J Med ; 2511-2521 ; 23 December 2010
Acute lymphoblastic leukemia: effect of mitoxantrone on outcome of children with first relapse
The authors report the results of a randomised trial undertaken in 31 centres in Ireland, the United Kingdom, Australia and New Zealand comparing the effects of idarubicine and mitoxantrone in induction in 216 children with acute lymphoblastic leukaemia(aged 1 to 18 years) who relapsed after a first complete remission. Compared to idarubicine, mitoxantrone significantly improved the progression-free and overall survival rates.
Read the PubMed abstract

To read more about "Acute lymphoblastic leukemia"

Lancet ; 2009-2017 ; 11 December 2010
Systemic sclerosis: limited efficiency of bosentan to treat digital ulcers
Digital ulcers (DU) are a frequent feature in systemic sclerosis patients. Preliminary studies highlighted a potential effect of bosentan, endothelin, a type A and B receptor antagonist, on DU several patients. This upscaled double blind, placebo controlled study involving 188 patients with at least one DU shows that bosentan reduces the occurrence of new DU but has no effect on DU healing.
Read the PubMed abstract

To read more about "Systemic sclerosis"

Ann Rheum Dis ; 32-38 ; January 2011
Rett syndrome: diagnostic criteria and nomenclature revised
The last consensus on Rett syndrome diagnostic criteria was established in 2002. Many clinical and molecular data have been collected since. In order to revise and clarify these criteria, the members of RettSearch have undertaken an iterative process to come to a new consensus to define the different forms of Rett syndrome and updated diagnostic criteria. Guidelines developed underline the need to diagnose Rett syndrome according to clinical criteria independently of possible molecular findings.
Read the PubMed abstract

To read more about "Rett syndrome"

Ann Neurol ; 944-950 ; December 2010

Orphan Drugs
CHMP adopts positive opinions recommending marketing authorisation for three orphan medicinal products in December
The Committee for Medicinal Products for Human Use (CHMP) at its December meeting adopted a positive opinion recommending marketing authorisation for three orphan medicines: Esbriet (pirfenidone), from InterMune Europe Ltd, intended for the treatment of idiopathic pulmonary fibrosis; Orphacol (cholic acid), from Laboratoires CTRS, intended for the treatment of inborn errors in primary bile acid synthesis due to 3β-Hydroxy-Δ5-C27-steroid oxidoreductase deficiency or Δ4-3-Oxosteroid-5β-reductase deficiency; and Teysuno (tegafur/gimeracil/oteracil), from Taiho Pharma Europe Ltd, intended for the treatment of advanced gastric cancer in adults when given in combination with cisplatin. The CHMP also reviewed the data on liver toxicity for orphan medicine Thelin (Pfizer) indicated for pulmonary arterial hypertension. Learn more

FDA extends indications for two rare disease products via accelerated approval process
In the USA, the Food and Drug Administration has approved a new indication for Afinitor (everolimus) from Novartis to treat subependymal giant cell astrocytoma associated with tuberous sclerosis in patients who cannot be treated via surgery. The FDA also approved extending the indication for Sprycel (dasatinib) from Bristol-Myers Squibb to treat Philadelphia chromosome positive chronic phase chronic myeloid leukaemia when it is first diagnosed. Both Afinitor and Sprycel received priority reviews from the FDA – an accelerated approval process that allows the FDA to “approve a drug to treat a serious disease with an unmet medical need based on an endpoint thought to reasonably predict clinical benefit”. Long-term efficacy and safety data will continue to be collected for both products.


Partnersearch, Job Opportunities
Postdoctoral position in human genetics
A post-doctoral position is available in Pr. Nicolas Levy’s research lab: UMRS_910 “Medical genetics and functional genomics” (Faculté de Médecine la Timone, Marseille, France). The position, provided by an AFM grant, is available for 24 months starting 1 February, 2011. The group’s research focuses on Hutchinson-Gilford Progeria and related premature aging syndromes linked to Lamin A/C mutations. A clinical trial for children affected with Progeria is ongoing in the Medical Genetics Department directed by Pr. Lévy at La Timone Children’s Hospital. Talented scientists with a solid background in molecular genetics, cell biology, bioinformatics and research on mouse models are encouraged to apply. A highly stimulating and interactive scientific environment with state of the art facilities and an active programme of seminars is provided. Fluent spoken and written English is required. Interested persons should send a cover letter, a full CV with bibliography and details of at least two referees to nicolas.levy@univmed.fr and Annachiara.DESANDRE-GIOVANNOLI@univmed.fr

Courses & Educational Initiatives

Course on practical clinical, radiological and pathological diagnosis of skeletal tumours
Organised by the European network of excellence EuroBoNeT in collaboration with Leiden University Medical Center and taking place from 14-16 February 2011in Leiden, the Netherlands, this course will focus on the use of clinical and radiodiagnostic data, and the pathological differential diagnosis of bone tumours. Practical training in the form of computerised microscopy training and discussion of relevant molecular biology techniques will form the core of the course. Orthopaedic surgeons, (trainee) pathologists, radiologists, clinical oncologists and paediatricians will particularly find this course useful.
For further details

Rare Solid Cancers: An Introduction
Organised by the European School of Oncology in collaboration with the Rare Care project. This course, being held in Stresa, Italy from 31 March – 1 April 2011, will focus on all the main rare solid cancers of the adult. Rare cancers present particular challenges, such as organisation of care and methodology of clinical studies. Oncologists, epidemiologists and health administrators will particularly find this course useful.
For further details

European Advanced Postgraduate Course in Classical and Molecular Cytogenetics
This ten-day course held in February/March each year is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. The students will be trained to identify genetic abnormalities for diagnosis and prognosis, and for fundamental and applied research using both classical and molecular cytogenetic techniques. The course is co-organised by the European Cytogeneticists Association and two French Universities, either as a stand-alone course with only the theoretical part or as a University Diploma including both theoretical and practical training. For further details
ESH Enerca Training Course on Haemoglobin disorders: Laboratory diagnosis and Clinical Management
In association with the Thalassaemia International Federation, this course, being held from 1-2 April 2011 in Brussels, Belgium, will address: Thalassaemias - Clinical and Molecular Aspects; Laboratory Diagnosis in Thalassaemia Syndromes; Sickle Cell Disease: Clinical Aspects; Abnormal Haemoglobins; Epidemiology of Haemoglobin Disorders; and more.
For further details

Update in Neuromuscular Disorders
Being held from 13-16 June 2011, at the Clinical Neuroscience Lecture Theatre, National Hospital for Neurology and Neurosurgery, in London, this established paediatric and adult course is now in its fourth year. Topics to include: What’s new in Duchenne muscular dystrophy?; Cognitive and behavioural profile of Duchenne MD; Psychological effects of participation in clinical trials; Cardiac involvement in neuromuscular disease; Congenital muscular dystrophies; Mitochondrial disorders – classification and genetic basis; and much more.
For further details

Master of Science in Haemoglobinopathy
A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy – such as counsellors, clinical psychologists, nurse specialists and midwives.
For further details

Orphan Academy 2011 programme
The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
For further details

EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
For further details


What's on Where?

2nd Annual Commercialisation & Market Access Strategies for Orphan & Ultra-Orphan Drugs
Date: 17 February 2011
Venue: Barcelona, Spain

The commercial event will be focused on orphan therapies and will guarantee all participants access to today’s most relevant case studies and views which directly affect their future business plans and can assist them to maximise market and patient access.
For further details

3rd International Adrenal Cancer Symposium: From Molecular Pathogenesis to Clinical Outcome
Date: 17-19 February 2011
Venue: Wurzburg, Germany

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. As a rare disease its molecular pathogenesis is still incompletely understood. Patients often suffer from delayed diagnosis and from insufficient follow-up. Treatment options remain unsatisfactory. This event aims to better understand the molecular mechanisms underlying ACC and to further improve patient care.
For further details

Fourth Berlin Conference on IP in Life Sciences: Rare Diseases – Blockbusters in the Niche
Date: 18 February 2011
Venue: Berlin, Germany

Leading experts in the field will share their knowledge on how to successfully bring orphan drugs to the market. This commercial event is of particular interest to representatives from biotech and pharmaceutical companies, researchers, business developers, clinical trial- and marketing experts, as well as investors, advisers and patent lawyers.
For further details

EUROPLAN Final conference
Date: February 25, 2011
Venue: Rome, Italy

The Final EUROPLAN Conference will present the main results obtained in the framework of the EUROPLAN project and will discuss further steps in the sector of the strategic national planning for rare diseases. The EUROPLAN coordinator, partners and invited speakers will illustrate the EUROPLAN Recommendations (focused on seven intervention areas reflecting the EU Council Recommendations), EUROPLAN Indicators (selected to monitor the implementation of national plans and strategies), and main results and suggestions from the national conferences organised by EURORDIS and the National Alliances of 15 European Member States.
For further details

4th International Symposium on Pulmonary Rare diseases and Orphan Drugs
Date: 25-26 February 2011
Venue: Milan, Italy

This event will explore issues in rare lung diseases and the development of orphan medicinal products and other therapeutic options for these disorders.
For further details

Third International Symposium on Paediatric Movement Disorders
Date: 25-26 February 2011
Venue: Barcelona, Spain

This event aims to continue the collaborative activities between professionals interested in paediatric movement disorders, mainly neurologists and neuropaediatricians. As in the previous symposiums qualified experts in the different aspects involved in paediatric movement disorders will increase knowledge, and serve to establish interesting contacts and develop creative ideas. Some newly recognised and treatable inborn errors of metabolism that may present with movement disorders in childhood (i.e. Glut-1 Deficiency, Cerebral Folate Deficiency and Dopamine Transporter Defects) will be presented.
For further details

Genetic Diseases of Children…Advancing Research & Care
Date: 7-9 March 2011
Venue: NY, USA

The conference will bring together over 1000 researchers, clinicians, affected families, government and industry leaders for the purpose of advancing research to improve health outcomes for children with genetic diseases.
For further details

Second ASID Congress of the African Society for Immunodeficiencies
Date: 10-13 March 2011
Venue: Hammamet, Tunisia

This second congress will be an excellent opportunity to strengthen the capacity of colleagues all over the continent to better diagnose and manage patients with PIDs. The commitment and contribution of international experts, societies and associations to this process is highly appreciated.
For further details

Human Genome Meeting 2011: Genomics of Human Diversity and Heritable Disorders
Date: 14-17 March 2011
Venue: Dubai, United Arab Emirates

Including symposia on the Genetics of Heritable Disorders; Cancer Genomics; Inborn Errors of Metabolism and Therapy of Genetic Disorders; Computational Biology and Statistical Genetics for the Analysis of Human Disease; Genetics of Deafness & Neurologic Disorders; and Advances in Genetics of Heritable Disorders.
For further details

11th International Congress of the European Society of Magnetic Resonance in Neuropediatrics
Date: 24-26 March 2011
Venue: Amsterdam, Netherlands

Bringing together neuroscientists, paediatric neurologists, scientists interested in developmental paediatrics, neonatologists, neuroradiologists, neuropsychologists, neurophysiologists and physicists to discuss the newest developments in advanced neuroimaging and image guided therapeutic approaches in the fields of normal and abnormal brain development and brain functions, which will be presented by internationally recognised experts.
For further details

CliniGene Network of Excellence: Gene Transfer and Therapy: State of the Art and eCHiPS - European Conference on Human iPS
7-9 April 2011
Paris, France

In the first part of this event the latest clinical data will be presented and the CliniGene platform leaders will report on the outcome and integration of various technologies. The eCHiPS - European Conference on Human iPS, organised jointly with several EU-networks, aims to offer an open forum gathering specialists with expertise in various aspects, such as reprogramming techniques, iPS markers, quality controls, industrial production, GMP constraints, clinical perspectives, predictive toxicology and high throughput screening, standardisation and regulation among others. The goal of this pivotal meeting is to promote a broader European collective action on iPS cells.
For further details

World Orphan Drug Congress USA 2011
Date: 13-15 April 2011
Venue: Washington DC, USA

This commercial event will bring together industry leaders, government, and research organisations to address the opportunities and challenges for the commercialisation of drugs to treat rare diseases.
For further details

Fourth International Congress of Myology
Date: 9-13 May 2011
Venue: Lille, France

Close to 1,000 participants coming from the five continents are expected to attend this conference to obtain an update on the scientific and medical advances made in muscle science and its related disorders. Two days will focus on fundamental science and two days on clinical research. The event will provide an opportunity to learn more about the numerous therapeutic avenues being explored and by the emerging clinical trials.
For further details

12th International Conference on Thalassaemia and the Haemoglobinopathies
Date: 11-14 May 2011
Venue: Antalya, Turkey

The main topics will include epidemiology and prevention; heart and vascular abnormalities; reproduction and pregnancy; quality care for quality of life; other haemoglobin disorders; haemopoietic stem cell transplantation; gene regulation and therapy; and much more. Deadline for abstract submission: 15 February 2011.
For further details

Ninth European Paediatric Neurology Society Congress
Date: 11-14 May 2011
Venue: Cavtat (Dubrovnik), Croatia

The programme includes basic neuroscience and neurobiology, new treatment approaches in muscular disorders, neuro-othology and neuro-opthalmology, advanced critical care and ethics in paediatric neurology as well as practical clinical knowledge in the skills of electroencephalography and electromyography via comprehensive workshops.
For further details

First International Symposium on Childhood, Adolescent and Young Adult Hodgkin Lymphoma
Date: 12-14 May 2011
Venue: Arlington, Virginia USA

This event seeks to: provide a platform for global collaboration; establish networks of multidisciplinary caregivers; identify leaders for specific projects; promulgate tools for communication and collaboration; and develop standards of care for children with HL.
For further details

Fifth Meeting on the Molecular Mechanisms of Neurodegeneration
Date: 13-15 May 2011
Venue: Milan, Italy

This International Congress is the Fifth Meeting of the series dedicated to the Molecular Mechanisms of Neurodegeneration in hereditary diseases. As in the previous edition, the Meeting is aimed at stimulating new and productive interactions among basic and clinical research groups involved in this exciting area of human genetics.
For further details

3rd Symposium on Disorders of Sex Development
Date: 20-22 May 2011
Venue: Lubeck, Germany

Disorders of Sexual Development (DSD) constitute a group of rare, mostly heritable disorders affecting the genito-urinary tract and in most instances also the endocrine-reproductive system. This symposium “From Gene to Gender” looks at what has been learnt and what is still needed. Sessions will focus on genetics, hormones and actions, phenotype modulation, clinical aspects and more.
For further details

Ninth Hereditary Hemorrhagic Telangiectasia International Scientific Conference
20-24 May 2011
Antalya, Turkey

This biennial conference, held since 1996, is attended by a multi-disciplinary, international group of clinicians, researchers and patient association representatives with the goal of advancing research and discoveries through multi-disciplinary "cross-fertilization" and international collaboration. An attendance of approximately 300 is expected.
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

VI Cornelia de Lange Syndrome World Conference
Date: 27-31 July 2011
Venue: Copenhagen, Denmark

Offering a professional symposium during which the latest developments in research, care and treatment will be discussed, as well as a family conference.
For further details

European Conference on Post Polio Syndrome
Date: 31 August – 02 September 2011
Venue: Copenhagen, Denmark

This international conference is being held by the European Polio Union, and The Danish Society of Polio and Accident Victims.
For further details

3rd International Symposium on Pheochromocytoma and Paraganglioma
Date: 14-17 September 2011
Venue: Paris, France

An opportunity to learn the state-of-the-art in pheochromocytoma and paraganglioma, to meet the leading experts in the field (coming from Europe, United States of America, Asia and Australia), to exchange and discuss the most recent research data as well as to develop international collaborative studies between clinical and/or academic research teams. This symposium takes place during a unique moment when key pathophysiological mechanisms and new therapeutic targets have been discovered and translated from bench to bedside. Deadline for abstract submission: 28 May 2011
For further details

5th International Conference on Birth Defects and Disabilities in the Developing World
Date: 24-27 September 2011
Venue: Lodz, Poland

The primary theme of the conference will be economics of healthcare and methods for establishing sustainable financial resources to implement programs of value to health and assure access to care. Other topics include integration of services into national primary health programs for care of neonates and children with birth defects and disabilities; monitoring risk factors for major defects globally; preconception care; and development of networks and partnerships for most efficient utilization of the limited resources.
For further details

Treat-NMD Global Conference
Date: 8-11 November 2011
Venue: Geneva, Switzerland

The conference will comprise a range of sessions addressing the challenges in the neuromuscular field, including: Delivery of future therapies; Biomarkers; Care considerations; Neuromuscular diseases and society; and Regulatory issues, orphan drugs and the rare disease field.
For further details


Orphanews Europe, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews Europe is supported by the European Commission's DG SANCO
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, 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)
For more information on the European Union Committee of Experts on Rare Diseases
Orphanet - All rights reserved