12 January 2011 print
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The New Year rings in resolutions across Europe to forward actions in the field of rare diseases and orphan drugs

At the beginning of this New Year, a time of resolutions, there is every reason to feel optimistic that the commitment to initiatives for rare disease patients and their families will continue to expand in 2011. Despite the gloomy economic climate still gripping much of the world, more European Union Member States are expected to come forward this year with a distinct strategy for their rare disease patients, in accordance with the Council Recommendation on an action in the field of rare diseases (learn more).

So many reasons for hope ...
One particularly bright spot on the horizon is the newly-formed European Union Committee of Experts on Rare Diseases (EUCERD), which convened for the first time in December to discuss a variety of activities promoting the understanding and treatment of rare diseases. Led by a team of experienced professionals, with the dedicated support of government at both the EU and Member State levels and the valuable input of stakeholders from medicine, research, government, patient organisations, and the biopharmaceutical industry, it is sure that via EUCERD initiatives in the field of rare diseases will progress in 2011.

Other important activities brewing include the CAVOD project, which is exploring the creation of a mechanism to exchange knowledge of the Clinical Added Value of Orphan Drugs between the Member States and EU-level authorities, in a bid to harmonise and accelerate the process of getting drugs to market in the Member States. There is also a new call for rare disease research proposals from E-Rare 2 (supported by the European Commission under the Seventh Framework Programme ERA-Net scheme), and the ongoing success of the Orphan Drug Regulation (141/2000) that encourages the development of medicinal products for rare diseases. The European Medicines Agency anticipates that a dozen orphan products will be authorised for marketing in 2011.

Furthermore, the successful Rare Disease Day, held on the last day of February, serves to deepen awareness around the world for the many issues rare disease patients and their families face – including a lack of diagnostics, treatment, and services. This year’s theme calls attention to the inequalities that rare disease patients encounter (learn more).

Overseas, the commitment to furthering efforts for rare disease patients is equally strong. A particularly productive meeting took place between rare disease research stakeholders from the USA and the EU in late 2010. Not wishing to lose momentum, a second meeting is already being planned for Spring 2011 that will seek to create an international consortium on rare diseases to prioritise and organise research. It is possible that Japan will also join this endeavour. In an article appearing in Nature Drugs Discovery last month, the FDA declared its commitment to accelerating orphan drug development (learn more).

Such rich evidence leads to the inevitable conclusion that 2011 will see an expansion of efforts designed to make life less difficult for millions of rare disease patients across Europe and around the world, as well as their families and all others who care - both professionally and personally.

Happy New Year from OrphaNews Europe


EU Policy News

EMA anticipates a dozen new orphan drugs will be authorised in 2011
The European Medicines Agency (EMA) has endorsed its work programme for 2011 and predicts a “stable number of applications for marketing authorisations” in the coming year, including twelve new orphan medicinal products. A press release reveals that “the special orphan medicines fund given by the EU has been reduced from €8.2 million to €4.9 million” under the new work programme. The EMA’s Management Board also adopted the new Road Map to 2015 (see OrphaNews Europe 24 February 2010 ) that takes into account the public consultation held in the first half of 2010 that brought responses from “EU institutions, Member States, and organisations representing patients and consumers, healthcare professionals, pharmaceutical industry, academia and health technology assessment bodies”. Finally, the Management Board thanked Executive Director of the Agency Thomas Lönngren, whose mandate ended on 31 December 2010, for ten years of leadership during which “…the Agency become one of the most recognised regulatory authorities in the world”. The 2011 work programme and the Road Map to 2015 will be published later this month.
New register for small- and medium-sized enterprises launches
The European Medicines Agency has launched a public register for small-and medium-sized enterprises (SMEs) that “aims at facilitating and promoting interaction amongst SMEs” by furnishing data, including contact information, areas of activity and number of employees, for SMEs registered with the agency. A second phase of the registry, available from the end of March 2011, will provide further details, including pipelines and product profiles. The new registry is part of a larger initiative to enhance transparency. It also reflects an ongoing effort of the EMA to support SMEs. The agency’s SME Office, established in 2005, encourages smaller European companies developing innovative new medicines, which are particularly promising to the field of rare diseases, by providing incentives and assistance, such as regulatory assistance, aid with translations, fee reductions, exemptions, and deferrals. The SME Office was the recipient of a 2010 European Mediscience Award for "Most significant contribution to the mediscience sector". Visit the SME Register

National & International Policy Developments
FDA declares its commitment to accelerating orphan drug development
A comment by members of the US Food and Drug Administration’s Office of Orphan Products Development and Office of New Drugs, appearing in Nature Reviews Drug Discovery, highlights new policy initiatives that aim to enhance progress in the developmental process of medicinal products for rare diseases in the USA. Accelerating Orphan Drug Development details the achievements of the Orphan Drug Act (1983) in the USA: over 2,250 orphan drug designations, of which 361 have received marketing approval. Furthermore, “in 2009, orphan drugs constituted 38% of the 29 new therapies that the US Food and Drug Administration (FDA) approved for marketing”. Of particular interest are initiatives to speed up the process of bringing products to market for rare conditions, which include the recently founded Rare Diseases Program within the Office of New Drugs of the FDA’s Center for Drug Evaluation and Research; the recently published report by the Institute of Medicine on accelerating rare disease drug development (learn more); and the FDA's internal Rare Disease Review Committee (mandated by the Section 740 Amendment), which is “currently performing a comprehensive analysis of current and projected practices for rare disease review and regulation at the FDA. The report describing the findings and recommendations of the review group is due to be presented to the US Congress in March 2011”. The article sums up by stating that the “FDA is committed to accelerating orphan drug development through a regulatory system built on integrity, consistency and transparency; a system that has delivered benefits to people who desperately need them and promises to deliver much more”. Consult the PubMed abstract

Orphan drug discounts for children’s hospitals in the USA saved by Medicare and Medicaid Extenders Act
Discounts on orphan medicinal products for children’s hospitals were menaced by a provision of the sweeping federal health care legislation overhaul enacted in the USA earlier this year. The provision prohibited independent children’s hospitals from accessing discounts to orphan drugs. However, the Medicare and Medicaid Extenders Act 2010 signed in by President Barack Obama on 15 December removes children’s hospitals from the orphan drug exclusion found in section 340B(e) of the Public Health Service Act, rendering the discounts once again accessible.
Other European news
Workshop considers issues surrounding medical devices in Europe
The European Medical Devices Workshop took place in late November in La Ciotat, France. This biennial event considers ongoing issues relating to medical devices, defined as any “instrument, apparatus, appliance, material or other article, whether used alone or in combination, together with any accessories or software for its proper functioning, intended by the manufacturer to be used for human beings in the: diagnosis, prevention, monitoring, treatment or alleviation of disease or injury; - investigation, replacement or modification of the anatomy or of a physiological process; - control of conception; and which does not achieve its principal intended action by pharmacological, chemical, immunological or metabolic means, but which may be assisted in its function by such means”. Many such devices have been developed for rare conditions. The 2010 workshop agenda paid particular attention to medical devices containing cell or tissue engineered material which fall within the scope of the European Medicine Agency’s Committee for Advanced Therapies. A symposium during the Workshop discussed the implementation of post-marketing evaluation for medical devices – required under the EU Directive 2007/47. Participants debated the elements post-marketing follow-up should contain. Would a European registry be advantageous and feasible? The Workshop also provided an interesting session comparing the way in which Europe and the Unites States define, encourage and manage devices for rare conditions. European medical devices are currently awarded EC marking when they meet criteria of specific European Council Directives. In contrast, the USA has the Humanitarian Device Exemption to facilitate access for small patient populations. Other incentives exist for medical devices developed for rare diseases. One problem that was pointed out with this system is that many devices can be applicable to both rare and common disorders. The next Workshop will take place in 2012.
Eleventh EPPOSI workshop yields eight expert recommendations for encouraging coordinated rare disease care across Europe
The eleventh Workshop on Partnering for Rare Disease Therapy Development of the European Platform for Patients’ Organisations, Science and Industry (EPPOSI) took place in late November in Prague. This year’s theme "Working together to define Research, Regulation and Realities for the EU Rare Disease Community" comes as EU Member States put together strategies for their rare disease patients that include collaboration and coordination with other Member States and with EU-level experts. Stakeholders from over 20 countries gathered for the annual event, held this year under the auspices of the Czech Ministry of Health. A press release noted that “…holding the event in Prague was particularly apt as it is countries from Central & Eastern European countries which, it emerged, are leading the way in putting in place the integrated frameworks to make this happen”.

While it was agreed that EU-level regulation was functioning, participants evoked the bottlenecks that exist at the Member State (MS) level. A plea for each of the 27 EU MS to elaborate a plan for rare diseases that includes cooperation and coordination was made. Professor Milan Macek, head of a leading Centre of Expertise in the Czech Republic (Charles University Prague) and President of the Czech Medical Genetics Society, commented that, “It is only by working together in this field that we stand any chance of moving forward. No one has all the solutions alone and where patients are rare, knowledge is rare and resources are rare, we need to put it all together to be successful”.

Eight specific recommendations were elicited to achieve this goal. These include the need for national plans that “…focus on a small number of key actions, integrated both vertically in the country as well as horizontally across countries, to create a true network that will make the most of scarce information and resources”. Other recommendations include the role of patients in “bridging the gap between physicians and politicians”; the “responsible engagement” of the biopharmaceutical industry; improved dialogue and collaboration between players; earlier communication between Health Technology Assessment bodies, regulators and payers; a mechanism to facilitate early access to orphan drugs against “a commitment to gather in-life data, conditional pricing and reimbursement”; the sharing of best practices; and safeguarding the successful EU Orphan Regulation (141/2000).
Consult the EPPOSI eleventh workshop speaker presentations

Other International News
Back by popular demand – International Rare Disease Day!
It is hard to believe that a year has already passed since the third International Rare Disease Day swept across the world, bringing attention to the issues concerning patients, families, caregivers, researchers and all others involved in improving conditions for rare disease patients. The fourth International Rare Disease Day will again take place on the final day of February. Coordinated by European rare disease patient umbrella organisation Eurordis, this year’s event has the slogan “Rare but Equal”. Activities to raise awareness are being planned by patients, professionals, government representatives, members of the biopharmaceutical industry and others. Participants from over forty countries are expected to join this year’s festivities. As in previous years, participants are invited to send their rare disease photos, videos and - a new feature in line with this year’s theme - Stories of Inequality, to the Rare Disease Day website. Learn more


EU Project Follow-up
New EU-funded registry seeks to improve diagnostics, care, knowledge and treatment for rare diabetes syndromes
EURO-Rare Diabetes is a newly launched project that will create a rare diseases registry for rare diabetes syndromes including Wolfram, Alstrom and Bardet Biedl. Funded by DG Sanco for 36 months, the project is being led by Prof Timothy Barrett (University of Birmingham, UK). Funded partner countries include Estonia, France, Italy, Poland, and Spain. Other collaborating partners are located in Denmark, Germany, Japan, Romania, and the USA.

Wolfram, Alstrom and Bardet Biedl (BBS) (WABB) syndromes (0.57, <0.2 and 0.8 cases/100,000 respectively; Orphanet Report Series Nov 2009 No. 1) are chronically debilitating and highly complex rare genetic diseases with clinical overlap (they can all cause diabetes mellitus, blindness and deafness). Affected people are distributed throughout the EU but disproportionately affect ethnic minorities. The diseases may progress to death in early adulthood. There are to date no orphan drug treatments available, nor access to well characterised cohorts of patients. The diseases show insights into common conditions (e.g. Wolfram variants and type 2 diabetes; Alstrom/BBS and obesity), but research is scarce and scattered in different laboratories throughout the EU. The lack of specific health policies for these diseases and the scarcity of expertise, translate into delayed diagnosis and difficult access to care. There are almost no multidisciplinary teams of experts in these diseases. Genetic testing centres are concentrated in a few member states, and there is unequal patient access to testing across the EU, America and Japan. The idea for the EURO-Rare Diabetes project came from Nolwenn Jaffre, President of the French Wolfram Association, who gathered Wolfram syndrome researchers from around the world in Paris in October 2009. The final application included researchers in Alstrom syndrome, Bardet Biedl syndrome, and Alstrom Syndrome UK as partners. The general objective of this project is to support efficient diagnosis, treatment, and research for the overlapping rare genetic diseases Wolfram, Alstrom and Bardet Biedl syndromes and other even rarer diabetes syndromes in Europe. The project will achieve this by implementing an EU registry for Rare Diabetes Syndromes (RDS), containing anonymised clinical, genetic diagnostic and outcome data. The purpose of the registry is: a) to establish the natural history of RDS (their characteristics, management and outcomes); b) to assess clinical effectiveness of management and quality of care; c) to provide a cohort of families interested in research who can be approached through their local doctors for participation in treatment studies; d) to establish if the genetic mutations can predict the complications or response to treatments. The project aims include rapid, readily available genetic testing; and up to date, accurate patient information, FAQS, and education material for health professionals.

Project partners will ask local doctors to approach affected families for consent to include their anonymised clinical data record in the Registry. The local doctor will control access to the records that he/she adds to the registry. Researchers will then apply to an oversight committee for permission to view the data records. If there is a new clinical trial of a treatment, the researcher will have to go through the local doctor for permission to approach his or her patients.

The leaders hope that this project will lead to an increase in the volume and quality of clinical research in RDS diseases. RDS diseases will have increased visibility to the research and health provider communities through Orphanet and EURORDIS. The anonymised data records will also serve to develop international guidelines on management of these diseases, and the Registry data will be used to assess the clinical effectiveness and cost-effectiveness of standard care and new interventions in a real-world setting. This will hopefully lead to improvements in quality of care. The Registry will also identify disparities between health care outcomes and provide evidence for health service providers for improvements.

Any health professionals inside or outside of the European Union caring for patients with one of these syndromes, as well as affected patients or family members, are urged to contact the project leader directly by email or via the project website. Regular news updates on how the project is progressing and how to get involved will be sent via email to register participants.


Orphanet News
New Texts
New Orphanet Journal of Rare Diseases publications
Acro-cardio-facial syndrome
The Schnitzler syndrome


New Syndromes

Infantile cerebral and cerebellar atrophy associated with a mutation in the MED17 gene
Primary microcephaly of postnatal onset is a feature of many neurological disorders, mostly associated with intellectual deficit, seizures, and spasticity, and typically carries a grave prognosis. Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation. Head circumference percentiles declined, and brain MRI disclosed marked cereberal and cerebellar atrophy with severe myelination defect. A missense mutation in the gene MED17 segregated with the disease state in the families and was carried by four of 79 anonymous Caucasus Jews. Screening of MED17 in additional patients with similar clinical and radiologic findings revealed four more patients, all originating from Caucasus Jewish families.
Read the PubMed abstract

Am J Hum Genet ; 667-670 ; 12 November 2010
Two phenotypically distinct 17p13.1 microdeletion syndromes with a common molecular mechanism
The authors report the association of a 17p13.1 copy-number variation, childhood-onset developmental delay (DD), and cancer. Through a screen of over 4000 patients with diverse diagnoses, they identified eight probands harbouring microdeletions at TP53 (17p13.1). Four patients were found to have a common phenotype including DD, hypotonia, and hand and foot abnormalities, constituting a unique syndrome. Notably, these patients were not affected with cancer. Moreover, none of the TP53-deletion patients affected with cancer (n = 4) had neurocognitive impairments. DD patients have larger deletions, which encompass but do not disrupt TP53, whereas cancer-affected patients harbor CNVs with at least one breakpoint within TP53. The authors conclude that, although they overlap, 17p13.1 CNVs are associated with distinct phenotypes depending on the position of the breakpoint with respect to TP53.
Read the PubMed abstract

Am J Hum Genet ; 631-642 ; 12 November 2010

New Genes

Carnevale, Malpuech, Michels and Oculo-Skeletal-Abdominal syndromes all have MASP1 mutations
Read the PubMed abstract
To read more about "Malpuech syndrome"
To read more about "Ptosis - strabismus - rectus abdominis diastasis"
To read more about "Michels syndrome"

Am J Hum Genet ; 679-686 ; 12 November 2010
Amyotrophic lateral sclerosis: exome sequencing reveals VCP mutations as a cause of familial form
Read the PubMed abstract
To read more about "Amyotrophic lateral sclerosis"

Neuron ; 857-864 ; 9 December 2010

Research in Action

Fundamental Research
Noonan syndrome: activation of multiple signalling pathways causes developmental defects in mice with a Sos1 mutation
Read the PubMed abstract
J Clin Invest ; 4353-4365 ; 1 December 2010
Dysferlinopathies: genetic ablation of complement C3 attenuates muscle pathology in dysferlin-deficient mice
Read the PubMed abstract
To read more about "Qualitative or quantitative defects of dysferlin"

J Clin Invest ; 4366-4374 ; 1 December 2010
Clinical Research
Addison disease in women is a risk factor for adverse pregnancy outcome
Read the PubMed abstract
J Clin Endocrinol Metab ; 5249-5257 ; December 2010
Juvenile idiopathic arthritis: do patients have an elevated risk of cancer?
Read the PubMed abstract
To read more about "Juvenile idiopathic arthritis"

Arthritis Rheum ; 3776-3782 ; December 2010
Muckle-Wells syndrome: patients at risk for severe form can be identified at time of diagnosis
Read the PubMed abstract
To read more about "Muckle-Wells syndrome"

Arthritis Rheum ; 3783-3791 ; December 2010
Gene Therapy
Amyotrophic lateral sclerosis: AAV4-mediated expression of IGF-1 and VEGF within cellular components of the ventricular system
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by motor neuron cell death in the cortex, brainstem, and spinal cord. Extensive efforts have been made to develop trophic factor-based therapies to enhance motor neuron survival; however, achievement of adequate therapeutic delivery to all regions of the corticospinal tract has remained a significant challenge. Here, the authors show that adeno-associated virus serotype 4 (AAV4)-mediated expression of insulin-like growth factor-1 (IGF-1) or vascular endothelial growth factor (VEGF)-165 in the cellular components of the ventricular system including the ependymal cell layer, choroid plexus [the primary cerebrospinal fluid (CSF)-producing cells of the central nervous system (CNS)] and spinal cord central canal leads to trophic factor delivery throughout the CNS, delayed motor decline and a significant extension of survival in SOD1(G93A) transgenic mice.
Read the PubMed abstract

To read more about "Amyotrophic lateral sclerosis"

Mol Ther ; 2075-2084 ; December 2010
Achromatopsia: restoration of cone vision in the CNGA3-/- mouse model
Congenital absence of cone photoreceptor function is associated with strongly impaired daylight vision and loss of color discrimination in human achromatopsia. Here, the authors introduced viral gene replacement therapy as a potential treatment in the CNGA3(-/-) mouse model. They show that such therapy can restore cone-specific visual processing in the central nervous system even if cone photoreceptors had been nonfunctional from birth. The restoration of cone vision was assessed at different stages along the visual pathway. Treated CNGA3(-/-) mice were able to generate cone photoreceptor responses and to transfer these signals to bipolar cells.
Read the PubMed abstract

To read more about "Achromatopsia"

Mol Ther ; 2057-2063 ; December 2010
Haemophilia B: high-efficiency transduction and correction using AAV2 vectors devoid of multiple surface-exposed tyrosines
Elimination of specific surface-exposed single tyrosine (Y) residues substantially improves hepatic gene transfer with adeno-associated virus type 2 (AAV2) vectors. Here, combinations of mutations in the seven potentially relevant Y residues were evaluated for further augmentation of transduction efficiency. These mutant capsids packaged viral genomes to similar titers and retained infectivity. A triple-mutant (Y444+500+730F) vector consistently had the highest level of in vivo gene transfer to murine hepatocytes, approximately threefold more efficient than the best single-mutants, and ~30-80-fold higher compared with the wild-type (WT) AAV2 capsids. Furthermore, Y730F and triple-mutant vectors provided a long-term therapeutic and tolerogenic expression of human factor IX in haemophilia B mice after administration of a vector dose that only results in subtherapeutic and transient expression with WT AAV2 encapsidated vectors.
Read the PubMed abstract

To read more about "Hemophilia B"

Mol Ther ; 2048-2056 ; December 2010
Therapeutic Approaches
Duchenne muscular dystrophy: laminin-111 is a potential therapeutic agent
Duchenne muscular dystrophy is caused by the complete loss of dystrophin from muscles. The lack of link between the contracting apparatus and the extracellular matrix leads to frequent damage to the sarcolemma, triggering muscle fiber necrosis. Laminins are major proteins in the extracellular matrix. Laminin-111 is normally present in skeletal and cardiac muscles in mice and humans but only during embryonic development. In this study, the authors show that intramuscular injection of laminin-111 increased muscle strength and resistance in mdx mice.
Read the PubMed abstract

To read more about "Duchenne and Becker muscular dystrophy"

Mol Ther ; 2155-2163 ; December 2010

Patient Management and Therapy

Cystic fibrosis: phenotype improvement via CFTR potentialisation by VX-770
The authors randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days (in part 2 of the study). The results showed that VX-770 was associated with within-subject improvements in CFTR and lung function.
Read the PubMed abstract

To read more about "Cystic fibrosis"

N Engl J Med ; 1991-2003 ; 18 November 2010
Gaucher disease: 2-year results of phase 2 study show improvement in haematological, visceral, and skeletal manifestations
Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy. Eliglustat tartrate improved clinical manifestations in patients who received 50 or 100 mg twice daily for 1 year during an open-label phase 2 study (Blood. 2010;116(6):893-899). After 2 years of treatment in 20 patients with baseline splenomegaly and thrombocytopenia and/or anemia, improvements from baseline occurred in platelet count, haemoglobin level, spleen volume, and liver volume. Lumbar spine bone mineral density increased, with major gains in osteoporotic and osteopenic patients. Magnetic resonance imaging assessment showed that bone marrow infiltration by Gaucher cells was decreased or stable. No safety-related trends emerged during 2 years of treatment.
Read the PubMed abstract

To read more about "Gaucher disease"

Blood ; 4095-4098 ; 18 November 2010
Congenital toxoplasmosis: prenatal treatment statistics for serious neurological sequelae
Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. The authors evaluated determinants of postnatal death or serious neurological sequelae defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment. Twenty-three of 293 (8%) foetuses developed serious neurological sequelae of which nine were pregnancy terminations. Prenatal treatment reduced the risk of serious neurological sequelae. The number of infected foetuses needed to be treated to prevent one case of serious neurological sequelae was three after maternal seroconversion at 10 weeks, and 18 at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce serious neurological sequelae compared with spiramycin alone. The proportion of live-born infants with intracranial lesions detected postnatally who developed serious neurological sequelae was 31.0%. The finding that prenatal treatment reduced the risk of serious neurological sequelae in infected foetuses should be interpreted with caution because of the low number of serious neurological sequelae cases and uncertainty about the timing of maternal seroconversion.
Read the PubMed abstract

To read more about "Congenital toxoplasmosis"

PLoS Med ; e1000351 ; 12 October 2010
European Society of Cardiology guidelines on the management of adult congenital heart disease
This article by the guidelines task force chairman of the European Society of Cardiology presents patient management and treatment recommendations for adult congenital heart disease. The recommendations are also available in Spanish language.
Read the PubMed abstract

Eur Heart J ; 2825-2833 ; December 2010
Pseudohypoparathyroidism type IA: recombinant human GH replacement therapy in children is better started early
Since the identification of GH deficiency due to resistance to GHRH in patients with pseudohypoparathyroidism type Ia (PHP-Ia), no study investigated the effects of recombinant human GH (rhGH) therapy on height velocity (HV) in these patients. The authors report the first study on the efficacy of rhGH replacement therapy in prepubertal children with PHP-Ia and provide indication that treatment of GH deficiency should be started soon due to the rather limited time window for a potentially effective therapy.
Read the PubMed abstract

To read more about "Pseudohypoparathyroidism"

J Clin Endocrinol Metab ; 5011-5017 ; November 2010

Orphan Drugs
Inside the “Orphanage” at the FDA
A concisely-written, open-access article published in the Journal of Cardiovascular Translational Research entitled the Orphanage at the FDA, outlines the role and responsibilities of the FDA’s Office of Orphan Product Development (OOPD), established in 1982. The OOPD does not determine which products should receive marketing authorisation, rather, it promotes “the development of products that demonstrate promise for the diagnosis, prevention, and/or treatment of rare diseases or conditions”. The author, from the OOPD’s Humanitarian Use Devices Designation Program, also details the designation criteria and potential incentives for developing medical devices for rare diseases via the Humanitarian Device Exemption. Some 50 products have been marketed through this route. The article also describes the Orphan Products Grants Program available for clinical trials involving drugs, biologics, devices and medical foods for rare conditions, and through which, “since 1983 more than 500 funded studies have yielded data that have brought 45 products to market”. A Pediatric Device Consortia Grant Program was also established in 2007, which funds “nonprofit consortia that create new pediatric medical devices linking innovators and manufacturers”. Currently, four such consortia receive funding.
Consult the open-access article

J of Cardiovasc Trans Res ; Epub ahead of print ; 16 November 2010
Committee for Orphan Medicinal Products ends 2010 with six new orphan designations
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 6 positive opinions issued at the December 2010 COMP meeting for the treatment of:

- renal cell carcinoma
- calciphylaxis
- prevention of arteriovenous access failure in haemodialysis patients
- epidermolysis bullosa
- oesophagus carcinoma
- haemophilia A

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


Partnersearch, Job Opportunities
Doctoral/Postdoctoral positions in human genetics
The groups of Dr Sébastien Jacquemont, Pr Jacques Beckmann and Pr Alexandre Reymond are working jointly on a large translational project covering genetics, genomics, neuroimaging, as well as clinical aspects aiming at the characterisation of the 16p11.2 rearrangements. Talented individuals with strong genetics skills and a background in molecular biology, bioinformatics, genomics or translational science/clinical research are encouraged to apply. Positions are available at the Department of Medical Genetics (DMG) and at the Center for Integrative Genomics (CIG) of the University of Lausanne, Switzerland. Both departments offer a stimulating, young and international environment with state-of-the-art facilities. For further details visit (DGM) and/or (CIG).
Interested persons can contact Sébastien Jacquemont

Research Fellow/Associate vacancies at EUROCAT Central Registry, University of Ulster, Belfast, UK
Three exciting opportunities have become available for researchers with a background in epidemiology and interest in maternal and foetal health. EUROCAT (European Surveillance of Congenital Anomalies) is a network of congenital anomaly registers in 20 European countries, funded by the European Commission Public Health Programme with a co-ordinating centre at the University of Ulster. EUROCAT surveillance and research concerns prevalence, causes and primary prevention, and prenatal screening. EUROCAT Central Registry is also a WHO Collaborating Centre for the Epidemiologic Surveillance of Congenital Anomalies. The EUROCAT co-ordinating centre is part of the Centre for Maternal, Fetal and Infant Research within the Institute for Nursing Research at the University of Ulster. EUROmediCAT (Safety of medication use in pregnancy in relation to risk of congenital anomaly) is a project under the umbrella of EUROCAT, funded by EU Seventh Framework Programme, a partnership of 9 institutions in Europe involved with pharmacovigilance, working with 13 congenital anomaly registries. The project will develop and test an efficient pharmaco-vigilance system for safety of medication use in pregnancy in relation to teratogenicity, and will focus on four medication groups of concern: antiepileptics, antidiabetics, antiasthmatics and antidepressants.
Project Manager, EUROCAT: fixed term Jan 2011 to Dec 2013, funded by EU DGSanco. The postholder will be responsible for the co-ordination and evaluation workpackages of the EUROCAT Joint Action programme and will be involved in a wide range of research and dissemination activities. A PhD or equivalent in public health or related area which includes a substantial epidemiology component is essential. Ref: 1171962
Research Fellow, EUROCAT: fixed term Jan 2011 to Dec 2013, funded by Northern Ireland Public Health Agency Research and Development Office. The postholder will develop a programme of research on the causes and prevention of congenital anomalies in Northern Ireland and Europe, as part of the EUROCAT Joint Action. A PhD or equivalent in public health or related area which includes a substantial epidemiology component is essential. Ref: 1171961
Research Associate, EUROmediCAT : fixed term March 2011 to Dec 2013, funded by EU Framework 7. The postholder will conduct research on the EUROmediCAT project to develop and test an efficient pharmacovigilance system for safety of medication use in pregnancy. He/she will in particular be responsible for work relating to risk of antidepressant use in early pregnancy. Ref: 1171956
Closing date for applications is 4 Feb 2011.
For further information, contact Professor Helen Dolk


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.
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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.
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EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
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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 market. This commercial event will be 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. OrphaNews Europe readers are being offered a discount of €100 from the €480 registration fee. To obtain this discount, enter "Orpha.net" in the "Discount Code" field of the online application.
For further details

EUROPLAN Final conference
Date: 25 February 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.
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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.
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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: 8-9 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.
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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. Deadline for abstract submissions: 24 January 2011
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 2010
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.
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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

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

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


Press & Publications
When the student is ready, the teacher appears:
new edition of clinical genetics text updates and expands material


New Clinical Genetics 2nd Edition updates the successful first edition of this text (published in 2006) which has proved essential reading for anyone interested in learning more and/or staying abreast of clinical genetics. The authors incorporate the latest advances in the rapidly evolving field and expand certain sections while retaining the original reader-friendly format of the text. Presented in a highly accessible format, New Clinical Genetics 2nd Edition provides a comprehensive overview of key elements using a series of clearly presented case studies to illustrate the main ideas of each chapter, which are cleverly woven throughout the text. Chapters focus on family history, the mechanics of the genes and DNA, the role of mutations, epigentics, rare versus common conditions, the impact of genes on the immune system, cancer, screening for conditions, and services available for genetic disorders. Each chapter outlines specific learning points, and includes self-assessment questions, a list of references, and handy “science toolkits” that explain the methods and concepts necessary to understanding the material. This text is a must-read for anyone wishing to stay current with the fast-paced field of clinical genetics.

Title: New Clinical Genetics 2nd Edition
Authors: A. Read and D. Donnai
Publisher: Scion Publishing, October 2010
ISBN: 9781904842804


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
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