WISHING ALL OUR READERS A VERY HAPPY NEW YEAR
Horizon 2020 call for proposals in the field of rare disease research
Horizon 2020 is the financial instrument implementing the Innovation Union, a Europe 2020 flagship initiative aimed at securing Europe's global competitiveness. It is the biggest EU Research and Innovation programme with nearly €80 billion of funding available over 7 years (2014 to 2020) – in addition to the private investment that this money will attract. It promises more breakthroughs, discoveries and world-firsts by taking great ideas from the lab to the market. Horizon 2020 is open to everyone, with a simple structure that reduces red tape and time so participants can focus on what is really important. This approach makes sure new projects get off the ground quickly – and achieve results faster.
Horizon 2020 has announced funding for many rare disease initiatives. The recently announced calls that is aimed to enhance research and development and build a knowledge structure in various areas of research including rare diseases research. The topics that include a budget for rare disease research are
-ERA NET rare disease research implementing IRDiRC objectives– aimed towards proposals that will coordinate national and regional programmes for research including rare disease research by preparing and implementing a transnational call with EU co-funding, resulting in grants to third parties, with a view to implement IRDiRC objectives and identified priorities. Successful grants will merit €40,000,000 and are expected to impact on national and transnational programmes and IRDiRC objectives as well as the leverage effect on European research and competitiveness, and should plan the development of key indicators for supporting this.
-New therapies for rare diseases- €€330,000,000 will be awarded to successful proposals that address one or more of the following: development of new or improved therapeutic approaches, for repurposing of existing therapies, as well as for preclinical research, animal model development and good manufacturing practice (GMP) production. Proposed treatments to be developed may range from small molecule to gene or cell therapy. Selected proposals should contribute to the objectives of, and follow the guidelines and policies of the International Rare Diseases Research Consortium, IRDiRC.
- Support for European Reference Networks: efficient network modelling and validation - proposals will provide coordinated support to the activities of the European Reference Network under the framework of Article 12 of Directive 2011/24/EU concerning implementation of a validated system methodology for the optimal organisation, governance, maintenance and continuous monitoring and evaluation of ERN and their centres. A budget of €29,000,000 has been made available for successful proposals in this area, some of which can be availed for research in rare diseases.
Additionally, to bring together, integrate on European scale, and open up key national and regional research infrastructures to all European researchers, from both academia and industry, ensuring their optimal use and joint development, Horizon 2020 will award grants towards research activities that will help towards -Integrating and opening existing national and regional research infrastructures of European interest. Out of several research areas, building research infrastructures to support rare diseases research is one of areas that will be supported under this topic. This initiative will be recognised as a “starting community” which invites proposals requesting a contribution from the EU of up to EUR 5 million would allow this topic to be addressed appropriately.
Genzyme sends letter of intent to join IRDiRC
Genzyme Corporation has presented the International Rare Disease Research Consortium (IRDiRC) steering committee with a letter of intent to support the IRDiRC objectives by being a part of the consortium. Genzyme, a Sanofi company, is willing to join the IRDiRC collaborative effort and supports the objectives of financing research for the treatment of rare diseases with an anticipated budget aligned with the IRDiRC scientific objectives, funding level, policies and governance structure. Genzyme has nominated Dr Carlo Incerti, SVP, Head of Global Medical Affairs to represent Genzyme on the IRDiRC Executive Committee and Seng Cheng, PhD Group Vice President, Genetic Diseases Science, to be a member of the International Scientific Steering Committee.
Go to the IRDiRC website
EMA
EMA offers further fee reductions for orphan drugs
EMA has announced greater fee reductions for large companies planning to market orphan drugs for rare diseases in the EU, thus further incentivising development of orphan medicinal products. The changes that will take effect in 2014, will offer reduced regulatory fees for larger companies and not just ones that are micro, small or medium-sized enterprises (SMEs). From next year, non-SME companies submitting a marketing application for an orphan drug will be eligible for a 75 per cent fee reduction for non-paediatric-related initial and follow-up protocol assistance. Previously this reduction was only 40 per cent for larger firms. The EMA will also introduce a 10 per cent fee reduction for initial marketing-authorisation applications, where currently there is no reduction. There will also be a 100 per cent reduction for pre-authorisation inspections, updating the current situation where no fee reduction is offered. These incentives are intended to encourage more pharma companies to enter the growing rare disease market, which has tended to be off-putting for drug makers due to the limited customer base. In addition to the fee reductions for larger companies, the EMA also confirmed the current financial assistance for SMEs. This includes free-of-charge services for all initial and follow-up protocol assistance, initial marketing-authorisation inspections and pre-authorisation inspections. Other incentives for orphan drug developers in the EU include ten years of market exclusivity and the chance to make a single marketing authorisation application the EMA.
Consult the fee reductions on the EMA website
EMA drug data will address HTA needs: a 3 year joint work plan is established
The European Medicines Agency (EMA) has agreed a three-year joint work plan with EUnetHTA, which represents health technology assessment (HTA) bodies across Europe in an effort to harness its relationship with national bodies such as UK's National Institute of Health and Care Excellence (NICE) that assess cost-effectiveness of drugs.
In this plan enhancement in collaboration was key, so that the work done by the EMA can assess the benefits and risks of a medicine for approval in the EU while at the same time addressing the needs of HTA organisations, which in turn assess the suitability of approved medicines for national reimbursement. However, the need for extended scientific advice and early dialogue between the EMA, HTA bodies and pharma companies was also commented in the plan. Also included in the plan is the exchange of ideas on the development of scientific and methodological guidelines to facilitate clinical-trial design that can generate data relevant to both parties. Additionally, collection of post-authorisation data once the drug is on the market and specific ways to share information on orphan drugs for rare diseases are also part of the plan.
This publication is part of a collaborative effort between the EMA and EUnetHTA initiated in 2010 to address the recommendations made by the Pharmaceutical Forum – a group comprising members from Member States, EU institutions, industry, healthcare professionals and patients.
Read the press release
Other European news
ECRIN awarded a European Research Infrastructure Consortium
On 29th November 2013, European Clinical Research Infrastructure Network (ECRIN) was officially awarded the Community legal framework for a European Research Infrastructure Consortium (ERIC). This specific legal form is designed to facilitate the joint establishment and operation of research infrastructures of European interest. ECRIN-ERIC will provide services to multinational clinical research, in any medical field and for any category of clinical research, observing high scientific, ethical and quality standards, in order to strengthen the capacity of the European Union to explore the determinants of diseases and to optimise the use of diagnostics, prevention and treatment strategies. National clinical research networks participating in ECRIN-ERIC currently cover 14 European countries representing about 400 million citizens. ECRIN-ERIC progressively expands throughout Europe with the support of a capacity building program facilitating the structuring of national networks and hubs. France, Germany, Italy, Portugal and Spain are members of ECRIN-ERIC that will be located in Paris. The official inauguration of ECRIN-ERIC will be on 30th January 2014, hosted by the French Permanent Representation in Brussels.
Visit the ECRIN website
Presenting the Dutch National Plan for Rare Diseases
On October 10, 2013, a delegation of The Netherlands Organization for Health Research and Development (ZonMw) presented the National Plan for Rare Diseases (in Dutch: Nationaal Plan Zeldzame Ziekten, NPZZ) to Minister Schippers of Health, Welfare and Sport (VWS). The National Plan for Rare Diseases is a further elaboration on and complement to the strategy the Minister sent to the parliament in February 2012. The Dutch National Plan identifies bottlenecks and recommendations, and it encourages field parties to feel responsible. The key bottlenecks for the plan include lack of knowledge about rare diseases, insufficient medical research on causes and course of rare diseases as well as inability of patient organisations to work well together. NPZZ recommends emphasising knowledge about rare disease through training and establishment of expert centers, make the information widely accessible to diverse audiences; make financial resources available for research and development of treatment as well as maintaining consistent policy for claims and reimbursement of orphan drugs. Finally NPZZ aims to appoint a director or coordinator to promote all recommendations, and avoid fragmentation and unnecessary duplication within the rare disease field.
Visit the Dutch Orphanet website
Other International News
Changes required for the gene therapy review panel in the United States: a panel report
After 4 decades of vetting clinical trials of gene therapy for novel risks, it’s time to relax a bit, says a report issued by an expert panel. But key government officials are greeting the recommendation with caution. The long-term hazards of gene therapy may not be clear yet, but the general risks seem no greater than in other areas of experimental medicine, the report says, so it’s time to phase out the U.S. outfit created in 1974 that’s dedicated to reviewing gene therapy, the Recombinant DNA Advisory Committee, or RAC. The report finds that “public perception has largely transitioned from negative to positive” thanks to gene therapy’s success in treating disorders such as inherited blindness and hemophilia. The panel urges the National Institutes of Health (NIH), which houses RAC and uses its advice, to stop having RAC examine individual gene therapy protocols. However, the report also recommends that while the old RAC should go out of business, another RAC-like body should take its place, and with a broader mandate—to examine all forms of risky clinical research that other agencies may not be able to vet adequately. This report is a result of last years, gene therapists main professional society’s public appeal to end RAC’s duplicate review, that is additional to NIH and FDA, is painful to many gene therapists. This appeal lead to NIH asking Institute of Medicine (IOM) to look into this matter, and the report issued today is the outcome of NIH’s request. NIH Director Francis Collins, after being briefed on the IOM report, issued a noncommittal statement today thanking the panel for its work but did not promise anything on the future of RAC.
Consult the article on Science
Rare voices Australia goes on the road to promote a National Rare Disease Plan for Australia
The number one priority for Rare Voices Australia (RVA) is to promote the adoption of a National Rare Diseases Plan for Australia. In 2011 the Australian Health Ministers Advisory Council (AHMAC) requested a Scoping paper on rare diseases. After two years of dedicated discussions with national coordinating committees, international meetings, engagement with those from across the rare disease sector as well as detailed reviews of literature and information gathering, a Scoping paper was released in 2013. AHMAC, however, did not collectively support the recommendation of the Scoping paper that Australia develop a National Rare Diseases Plan. Although Western Australia and Northern Territory confirmed their written support for a National Plan for Rare Diseases other states and territory chose not to espouse the plan. AHMAC requested more information on the status of genetic testing, disease coding and clinical pathways.
Despite this setback, RVA has not lost hope, as in 2014 they have planned a roadshow with the goal to increase engagement with the jurisdictions of states in order to gain further understanding on what is needed in order to get full support for a National Rare Diseases Plan in Australia. In each of the 5 states, RVA has planned a half day seminar conducted by an independent facilitator giving opportunity for Patient Organisation leaders to provide their valued feedback while the other half day seminar will be designed and facilitated for a specific group being the Executive leaders, policy makers and advisors in health who will be individually invited to give their valued feedback on the need for a National Plan for Rare Diseases. The timetable of Roadshow Dates (Patient Organisation Leaders) is available on their website.
Guidance Documents and Recommendations
Recommendations for screening and detection of connective tissue disease–associated pulmonary arterial hypertension
Arthritis Rheum. ; 65(12):3194-201 ; December 2013
General Terms for Congenital Anomalies that will aid our understanding of human development
In an article published in American Journal of Medical Genetics, the authors define and illustrate the general terms that describe congenital anomalies as related to human conditions. An international group of clinicians working in the field of dysmorphology has established a process for the standardization of terms used to describe human morphology. The goals are to standardize these terms and develop consensus regarding their definitions. According to the authors, this project will increase the usefulness and precision of descriptions of the human phenotype and facilitate reliable comparisons of phenotypic findings among clinicians and researchers in medicine, developmental biology, and genetics. They have presented a series of definitions is part of an iterative process following on several earlier definitions of these general terms. From this project the authors concluded that updating the terms was necessary due to recent advances in our understanding of molecular genetics and human development. They anticipate that additional future insights will lead to further evolution of the definitions.
Consult the PubMed abstract
Screening and Testing
DNA Sequencing-Based Non- Invasive Prenatal Testing (NIPT) for Fetal Aneuploidy is regarded positively by women in Hong Kong
A qualitative study published in PLOS One aims to explore women’s motivations for using, and perceptions of, DNA-NIPT in Hong Kong. In-depth interviews were conducted with 45 women who had undertaken DNA-NIPT recruited by purposive sampling based on socio-demographic and clinical characteristics. The sample included 31 women identified as high-risk from serum and ultrasound based Down syndrome screening (SU-DSS). Thematic narrative analysis examined informed-decision making of the test and identified the benefits and needs. The authors reported the number of reasons described by women for accessing DNA-NIPT which included reducing the uncertainty associated with risk probability based results from SU-DSS, undertaking DNA-NIPT as a comprehensive measure to counteract risk from childbearing especially at advanced age, perceived predictive accuracy and absence of risk of harm to fetus. According to the authors accounts of women deemed high-risk or not high-risk are distinctive in a number of respects. High-risk women accessed DNA-NIPT to get a clearer idea of their risk and they perceived SU-DSS as an unnecessary and confusing procedure because of its varying, protocol-dependent detection rates. The authors also reported that those women not deemed high-risk, in contrast, undertook DNA-NIPT for psychological assurance and to reduce anxiety even after receiving the negative result from SU-DSS. In conclusion the authors believe that DNA-NIPT was regarded positively by women who chose this method of screening over the routine, less expensive testing options. The authors recommend further development of guidelines and quality assurance will be needed to provide a service suited to patients’ needs.
Consult the PubMed abstract
An expert opinion document to start debate on newborn screening policies and an article in Science debating the pitfalls of newborn screening
An expert opinion document has been published in European Journal of Human Genetics on policies that will augment newborn screening methods and practices across Europe. This article is based on what has been already delineated in the European Commission’s tender on newborn screening to report on current practices of laboratory testing, form a network of experts and provide guidance on how to further implement NBS screening in a responsible way.
Consult the PubMed abstract
Another article published in Science describe certain serious drawbacks of newborn screening. Apart from a lack of evidence about screening for most disorders, the author also illustrates how rarity of a disease makes assessing benefit difficult. The author points that far more cases are detected by screening than are detected clinically among patients presenting for medical attention with symptoms. Thus groups of screened and unscreened patients are not comparable: Screened groups may include those with milder cases, possibly never destined to become symptomatic; unscreened groups may include never-diagnosed deceased patients. The author warns that comparisons must be between whole populations, not simply between screened and unscreened affected subjects, which greatly reduces statistical power. Another important drawback reiterated by the author involves the significance or probable age of onset of symptoms in some cases is unknown. The harms likely from newborn screening largely relate to the worry caused by false positive results or, worse, results of uncertain significance—which leave parents in limbo, uncertain whether or not their child is affected—and to over medicalication in cases where treatment is not needed, with attendant anxiety and costs of unnecessary clinical care. The author alerts that these are not trivial issues and are sure to increase if, in the near future, newborns are screened by whole-genome, exome, or more targeted genetic sequencing. Additionally the author describes the pitfall of one test detecting many disorders where benefit may seem clear-cut for one disorder, but for others, detected in the same test for almost no added cost, there may be more harm than benefit. The author also delineates the difficulties in newborn screening distinguishing severe early-onset phenotypes from adult-onset or benign ones. Thus although newborn screening may be beneficial in some cases, the author advises to err on the side of caution.
Access the article
Orphanet report series update
Orphanet has published List of Research Infrastructures useful to Rare Diseases in Europe. This useful list is arranged by country and provides an exhaustive list of facilities that are extremely vital for rare disease research.
Orphanet performs a systematic survey of the literature to provide an estimate of the prevalence of rare diseases in Europe. You can find a recently updated list on Prevalence of rare diseases: Bibliographic data on the Orphanet website. This update contains new epidemiological data and modifications to existing data for which new information has been made available.
New Research Projects open for Recruitment
DECIPHER invites membership from interested parties who wish to benefit from data sharing
Interpreting rare or novel genomic variants is a major challenge that is increasing as clinical teams change their focus from individual genes, to gene panels and/or whole exome/genome sequencing. Sharing data on phenotype, genotype and inheritance is crucially important to develop the evidence base required for accurate interpretation of rare variants and to facilitate new gene discovery. In many cases, the data needed to interpret a variant will not be found within a single clinical centre, and so sharing data between clinical centres is critical for delivering diagnoses. To enable this data sharing, the Wellcome Trust funded DECIPHER web portal (http://decipher.sanger.ac.uk/
Contact requested from patients with Hajdu-Cheney Syndrome
Hajdu-Cheney syndrome (HJCS:OMIM 102500) is a rare genetic disorder characterised by generalised (osteoporosis) and focal (acro-osteolysis) bone loss, variable congenital abnormalities, faltering growth and dysmorphic features. Autosomal dominantly transmitted mutations in the gene encoding Notch2 cause HJCS.Current medical management is through the use of the bone anti-resorptive agents, bisphosphonates, such as disodium pamidronate, to maintain bone mass. The treatment may not always be effective, nor does it prevent or improve the acro-osteolysis, which necessitates the development of new treatment options. Dr Melita Irving and her team at Guy's Hospital and King's College, London, UK are seeking to determine the incidence of Hajdu Cheney Syndrome worldwide to help inform a drug development programme. They are keen to hear about any known patients and affected relatives to help gauge the number of individuals with the condition. Contact Dr. Melita Irving for more information
δPI3K- gene mutation predisposes to a new syndrome of primary immunodeficiency characterized by respiratory infection and airway damage
The authors described a new syndrome of primary immunodeficiency due to PIK3CD gene mutation which was associated with recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, and reduced immunoglobulin G2 levels in serum and impaired vaccine responses.
Consult the Pubmed abstract
Science ; 342(6160):866-71 ; November 2013
A novel prion disease associated with diarrhea and autonomic neuropathy
The authors identified a PRNP Y163X truncation mutation and described a novel prion disease associated with a distinct and consistent phenotype of chronic diarrhea with autonomic failure and a length-dependent axonal, predominantly sensory, peripheral polyneuropathy with an onset in early adulthood. Cognitive decline and seizures occurred when the patients were in their 40s or 50s.
Consult the Pubmed abstract
N Engl J Med. ; 369(20):1904-14 ; November 2013
A novel syndrome of macrocephaly, neurodevelopmental delay, and seizures due to mutations in KPTN
The authors reported on families from the Amish community of Ohio with mutations in KPTN causing a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures.
Consult the Pubmed abstract
Am J Hum Genet. ; [Epub ahead of print] ; November 2013
Autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation in two individuals of a consanguineous Turkish family
The authors presented a consanguineous Turkish family with two affected individuals presenting with short stature, distinct facial features, alterations of fat distribution, and moderate intellectual disability, associated to a homozygous missense mutation in XYLT1.
Consult the Pubmed abstract
Hum Genet. ; [Epub ahead of print] ; August 2013
Novel muscle–eye–brain disease-like phenotype with multicystic leucodystrophy linked to a homozygous DAG1 mutation
The authors identified a homozygous novel DAG1 missense mutation in two Libyan siblings. The affected girls presented a novel clinical phenotype with a severe muscle–eye–brain disease-like phenotype with distinct additional findings of macrocephaly and extended bilateral multicystic white matter disease, overlapping with the cerebral findings in patients with megalencephalic leucoencephalopathy with subcortical cysts.
Consult the Pubmed abstract
Neurogenetics ; 14(3-4):205-13 ; November 2013
Predisposition to severe early-onset obesity could be due to KSR2 and CEP19 mutations
Cell ; 155(4):765-777 ; October 2013
Am J Hum Genet. ; 93(6):1061-71 ; December 2013
Am J Hum Genet. ; 93(6):1061-71 ; December 2013
Warburg micro syndrome is associated with TBC1D20 loss-of-function mutations
Am J Hum Genet. ; 93(6):1001-14 ; December 2013
Myopathy and hereditary sclerosing poikiloderma with tendon and pulmonary involvement due to missense mutations in FAM111B
Am J Hum Genet. ; 93(6):1100-7 ; December 2013
Recessive auriculo-condylar syndrome and dominant isolated question-mark ears caused by mutations in EDN1
Am J Hum Genet. ; 93(6):1118-25 ; December 2013
Myofibrillar disruption in Nemaline myopathy linked to small deletions and missense changes in KLHL41
Am J Hum Genet. ; 93(6):1108-17 ; December 2013
Foveal hypoplasia and optic nerve misrouting without albinism caused by recessive mutations in SLC38A8
Am J Hum Genet. ; 93(6):1143-50 ; December 2013
Short stature, auditory-canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS syndrome) results from GSC mutations
Am J Hum Genet. ; 93(6):1135-42 ; December 2013
Familial idiopathic hyperprolactinemia, a condition associated with oligomenorrhea and infertility, is due to a heterozygous mutation in PRLR
N Engl J Med. ; 369(21):2012-20 ; November 2013
ACTH-independent macronodular adrenal hyperplasia with Cushing’s syndrome linked to ARMC5 mutations
N Engl J Med. ; 369(22):2105-14 ; November 2013
Autosomal recessive primary microcephaly associated with a homozygous single nucleotide substitution in CDK6 in a large Pakistani family
Hum Mol Genet. ; 22(25):5199-214 ; December 2013
Congenital myopathy: identification of a homozygous non-sense mutation in HACD1 in affected individuals in a consanguineous family
Hum Mol Genet. ; 22(25):5229-36 ; December 2013
A new congenital disorder of glycosylation characterised by microcephaly, intellectual disability, gastroesophageal reflux, and seizure disorder caused by SSR4 mutation
Hum Mol Genet. ; [Epub ahead of print] ; November 2013
Autosomal dominant nuclear cataract associated to WFS1 mutation
Eur J Hum Genet. ; 21(12):1356-60 ; December 2013
Autosomal recessive aplastic anemia: exome sequencing revealed a novel homozygous mutation in THPO in a Micronesian family
Blood ; 122(20):3440-9 ; November 2013
Isolated truncus arteriosus linked to a homozygous mutation in PLXND1
Am J Med Genet A. ; 161(12):3115-20 ; December 2013
Familial Ebstein malformation, left ventricular hypertrabeculation, and ventricular septal defect associated with a MYH7 mutation
Am J Med Genet A. ; 161(12):3187-90 ; December 2013
Early-onset encephalopathy, lactic acidosis, and severe reduction of mitochondrial complex III activity due to a homozygous mutation in LYRM7/MZM1L
Hum Mutat. ; 34(12):1619-22 ; December 2013
Hypertrichotic osteochondrodysplasia: identification of a mutation in KCNJ8 in a patient with unique vascular abnormalities
Eur J Med Genet. ; 56(12):678-82 ; December 2013
West-syndrome evolving to Lennox-Gastaut syndrome: whole-exome sequencing identified a heteroplasmic variant in MTND1
Hum Mutat. ; 34(12):1623-7 ; December 2013
Mild autosomal dominant non-syndromic intellectual deficit in a girl with a de novo deletion of FMN2
Eur J Med Genet. ; 56(12):686-8 ; December 2013
Acute lymphoblastic leukemia: inherited GATA3 variants and PIP4K2A variants as risk factors
Nat Genet. ; 45(12):1494-8 ; December 2013
Blood ; 122(19):3298-307 ; November 2013
Blood ; 122(19):3385-7 ; November 2013
Blood ; 122(19):3298-307 ; November 2013
Blood ; 122(19):3385-7 ; November 2013
Behçet disease: a high copy number of C4A confers risk for the disease in the Chinese population
Arthritis Rheum. ; 65(11):2963-70 ; November 2013
Systemic sclerosis: a regulatory variant in CCR6 is associated with susceptibility to the disease
Arthritis Rheum. ; 65(12):3202-8 ; December 2013
Susceptibility to non-syndromic oral cleft malformations linked to fetal polymorphisms at the ABCB1 gene
Eur J Hum Genet. ; 21(12):1436-41 ; December 2013
Clinical Research
Waldenström macroglobulinemia: bortezomib, dexamethasone, and rituximab combination in previously untreated symptomatic patients is rapidly acting and well tolerated
Blood ; 122(19):3276-82 ; November 2013
Polymyositis and dermatomyositis: improvement in health and possible reduction in disease activity using endurance exercise
Arthritis Care Res. (Hoboken) ; 65(12):1959-68 ; December 2013
Ehlers-Danlos syndrome, hypermobility type: phase 1 study combining physical and cognitive-behavioral therapy increases muscle strength and endurance in 12 women
Am J Med Genet A. ; 161(12):3005-11 ; December 2013
Burkitt lymphoma: low-intensity EPOCH-R–based treatment (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, rituximab) was highly effective in adults
N Engl J Med. ; 369(20):1915-25 ; November 2013
Glioblastoma: improved tumor oxygenation and survival in patients who showed increased blood perfusion after cediranib and chemoradiation
Proc Natl Acad Sci U S A. ; 110(47):19059-64 ; November 2013
Small cell lung cancer: evaluation of amrubicin
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 1041-1047 ; December 2013
Autosomal recessive early-onset inflammatory bowel disease: a Mendelian predisposition caused by interleukin-10 receptor deficiency
Blood ; 122(23):3713-22 ; November 2013
Indolent T-cell lymphoproliferative disease of the gastrointestinal tract not to be mistaken with aggressive T-cell lymphoma
Blood ; 122(22):3599-606 ; November 2013
Glaucoma: a review on pediatric terminology
Am J Med Genet A. ; 161(12):3205-15 ; December 2013
Gene Therapy
Duchenne muscular dystrophy: micro-dystrophin and follistatin co-delivery restores muscle function in aged mouse models
Hum Mol Genet. ; 22(24):4929-37 ; December 2013
Hemophilia A: Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A
Nat Commun. ; 19;4:2773 ; November 2013
Hemophilia B: systemic adeno-associated virus vector delivery of zinc finger nucleases and corrective donor to adult mouse liver results in stable human factor IX levels
Blood ; 122(19):3283-7 ; November 2013
Fragile X syndrome: acute depletion of CPEB1 in the hippocampus of adult Fmr1-/y mice rescued working memory deficits
Nat Med. ; 19(11):1473-7 ; November 2013
Therapeutic Approaches
Myelofibrosis with myeloid metaplasia: retinoid antagonist normalized thrombopoietin production, restored bone integrity and reduced fibrosis in a mice model
Proc Natl Acad Sci U S A. ; 110(47):18820-5 ; November 2013
Osteoporosis – pseudoglioma: sclerostin inhibition reversed skeletal fragility in an Lrp5-deficient mouse model
Sci Transl Med. ; 5(211):211ra158 ; November 2013
Duchenne muscular dystrophy: reducing CTGF/CCN2 slows down mdx muscle dystrophy and improves cell therapy in mdx mouse model
Hum Mol Genet. ; 22(24):4938-51 ; December 2013
αCongenital muscular dystrophy type 1A: recovery of laminin-2 chain and slightly prolonged life with PMO-mediated exon skipping in mouse model
Hum Mol Genet. ; 22(24):4914-28 ; December 2013
αInflammatory myopathy: the inhibition of the ubiquitin proteasome pathway with bortezomib improved muscle function and reduced tumor necrosis factor in a mouse model
Arthritis Rheum. ; 65(12):3248-58 ; December 2013
Diagnostic Approaches
Clinical and laboratory features distinguishing juvenile polymyositis and muscular dystrophy
Arthritis Care Res. (Hoboken). ; 65(12):1969-75 ; December 2013
Special issue on rare bleeding disorders: genetic, laboratory, clinical and molecular aspects
Seminars in Thrombosis and Hemostasis ; 6(39) ; September 2013
Congenital myasthenic syndromes: an update
Curr Opin Neurol. ; 26(5):561-8 ; October 2013
Kienbock disease: a review
Orthop Clin North Am. ; 45(1):141-52 ; January 2014
Neuronal ceroid lipofuscinosis: review on the advances in the treatment
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 951-975 ; December 2013
Polycythemia vera: review on the state-of-the-art treatment
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 977-985 ; December 2013
Narcolepsy: review on the treatment options
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 987-999 ; December 2013
Mantle cell lymphoma: a review
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 1001-1018 ; December 2013
Primary effusion lymphoma: review on new approaches to treatment
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 1019-1029 ; December 2013
Cystinosis: review on main clinical features and on current and experimental treatments
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 1031-1039 ; December 2013
Essential thrombocythemia: evaluation of anagrelide hydrochloride
Expert Opinion on Orphan Drugs ; Vol. 1, No. 12 , Pages 1049-1062 ; December 2013
Cerebellar ataxia: consensus paper on the management of degenerative cerebellar disorders
Cerebellum ; [Epub ahead of print] ; November 2013
Von Willebrand disease: review on advances in pathogenetic understanding, diagnosis, and therapy
Blood ; 122(23):3735-40 ; November 2013
Idiopathic aplastic anemia: review on the treatment options
Blood ; 122(22):3561-7 ; November 2013
Glycogen storage disease: all patients with infantile-onset should undergo polysomnography as a routine part of their care
Am J Med Genet A. ; 161(12):3196-200 ; December 2013
One new Clinical Utility Gene Card published in the European Journal of Human Genetics
EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases.
The European Journal of Human Genetics has published one new Clinical Utility Gene Card for:
Hyperlipoproteinemia type 2
Political and Scientific News
Study describes the use of Multicriteria Decision Analysis for Valuing Orphan Medicines
An article published in Orphanet Journal of Rare Diseases studied the use of multicriteria decision analysis (MCDA) to establish and apply a framework of weighted attributes to value orphan medicinal products. The study involved literature searches on the natural history and burden of 40 rare diseases and of how payers assess treatment value and three workshops with, respectively, GlaxoSmithKline managers working on orphan medicinal products, European Union clinical and health economics experts, and representatives of rare diseases patient groups in the European Union. The authors identified 8 non-monetary attributes and weights agreed on four concerns for the disease being treated and four for the treatment itself. About half of the weight went to attributes of the disease treated and half to attributes of the treatment. Patient group representatives gave greater weight than did the experts to patients’ and carers’ quality of daily life. According to the authors, the multicriteria decision analysis approach could be developed for use by payers and health technology assessment bodies. The authors have stated that "given the intrinsically complex nature of the rare diseases and OMPs environment, an MCDA approach for rare disease treatment value assessment has the merit of ensuring shared understanding of the elements of value as well as a clear articulation of trade-offs between those elements". The authors have piloted such an approach with patient group representatives and clinical and health economics experts who advise HTA bodies and payers. They believe that the MCDA approach offers a possible construct for more comprehensive guidance to HTA and P&R decision making.
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An analysis of drug development for exceptionally rare metabolic diseases
In an article published in Orphanet Journal of Rare Diseases, the authors studied the extent to which the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). To study this, the authors collected all metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population from the ’Orphanet database of Rare diseases’. The outcome of interest was the application for an orphan designation at FDA or EMA. The authors described the level of publicly available knowledge of the disease and drug candidate before an orphan designation application, as whether "the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans". The authors also included other determinants in the study such as metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. The authors identified, 166 rare metabolic genetic diseases, which were included in the analysis. The authors report that their analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation. The authors have stated that "this study shows that for low prevalence rare metabolic diseases preclinical proof of concept of drug candidates and disease prevalence play an important role in the translation of disease knowledge into an orphan drug development program".
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A cost-based yardstick approach for pricing orphan drugs to reduce the burden on patients
An article published in Orphanet Journal of Rare Diseases explores the use of a cost-based price control mechanism for orphan drugs, adapted from the standard models applied in utilities regulation. Manufacturers justify the high prices for orphan drugs on the basis that the associated R&D costs must be spread over few patients. The proliferation of these drugs in the last three decades, combined with high prices commonly in excess of $100,000 per patient per year are placing a substantial strain on the budgets of drug plans in many countries. The authors in this article suggest a cost-based regulatory mechanism where a rate-of-return style model, employing yardsticked cost allocations and a modified two-stage rate of return calculation could be effective in setting a new standard for orphan drugs pricing. According to the authors, this type of cost-based pricing would limit the costs faced by insurers as well as patients while continuing to provide an efficient incentive for new drug development.
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The 6th Joint Call for European research projects on rare diseases (E-Rare)
E-Rare has announced its 6th Joint Transnational Call for Research Projects on Rare Diseases (JTC 2014). 16 countries will participate in this call: Austria, Belgium (Flanders), Canada (including Québec), France, Germany, Hungary, Israel, Italy, Latvia, Poland, Portugal, Romania, Spain, Switzerland, The Netherlands and Turkey. This year the call is specifically dedicated to the development of innovative therapeutic approaches for rare diseases. The aim of the call is to enable scientists in different countries to build an effective collaboration on a common interdisciplinary research project based on complementarities and sharing of expertise, with a clear translational research approach. Projects shall involve a group of rare diseases or a single rare disease following the European definition (a seriously debilitating and/or life-threatening disease affecting not more than 5 in 10.000 people). The research projects must focus on the pre-clinical development of therapeutic approaches in suitable existing animal or cell models. Therapeutic approaches can include (but are not limited to): cell based therapy; gene therapy and pharmacological therapy.
Rare infectious diseases, rare cancers and rare adverse drug events in treatment of common diseases are excluded from the scope of the call.
The deadline for pre-proposal submission is 30 January 2014.
For further information
SMA Europe announces its 6th international Call for SMA Research Projects
This new Call for SMA Projects will be open to any research project aimed at finding a therapy for Spinal Muscular Atrophy (SMA) or at elucidating the basic pathophysiological processes of the disease. The overall goal of SMA Europe is to help the dedicated international scientific and medical community in its search for therapies for SMA. Time being critical for people with SMA, preferences will be given to projects that have the greatest potential to overcome barriers to translation of advances in basic science and to accelerate the identification of effective treatments. For more information please visit the SMA Europe web site
Myotubular Trust - Sixth call for projects (open to international applications)
The Myotubular Trust is holding a sixth call for research projects. The trust is looking to fund further projects that will help find a cure and / or a treatment for any of the three types of myotubular myopathy (congenital X-linked recessive; congenital autosomal recessive; autosomal dominant), focusing on research that would not generally be funded by public or industrial funding sources. This call will be open to research bodies internationally.
The Myotubular Trust will be looking for the following types of application:
1. A project grant applied for by a Principal Investigator to fund a project for 2-3 years duration to be carried out by a Post Doctoral researcher, or PHD student.
2. A Myotubular Trust fellowship – basic science (3-4 years duration), where the scientist has identified a group that he or she wants to work with. Award is made to a named individual.
In particular the trust would like to encourage the application of new technologies to research into myotubular myopathy, which may involve collaboration between different medical disciplines and / or different research institutions. The trust is also willing to consider applications which involve joint funding with other organisations. Click here for more information or email research@myotubulartrust.org
Application deadline: Friday 17th January 2014.
Group leader positions in the Imagine Institute of Genetic Diseases
The new Imagine Institute of Genetic Diseases, affiliated with the Necker Enfants maladies Hospital campus Paris, is inviting applications for group leader positions. Imagine is an interdisciplinary research center with excellent core facilities for genomics, cell imaging, flow cytometry, bioinformatics, pathophysiology and animal housing for transgenic mice and zebra fish. The new tailor-made building (to be opened in early January 2014) will offer cutting-edge research facilities. The Institute focuses on rare diseases, their genetic architecture and life-long outcomes. Imagine intends to address unmet basic and clinical research questions related to rare diseases, in order to increase knowledge in a major medical field that is currently insufficiently covered. This will result in the development of new biological concepts, diagnostic tools and innovative therapeutics. Applications can focus on any field directly linked or related to the basis, pathophysiology and treatment of genetic diseases, with special emphasis on:
1- Development, stem cells and neuroscience.
2- Computational biology and/or bioinformatics.
Applications in these two areas will be separately evaluated. Appointments will be made at a junior or senior level, depending on experience. Applications should be submitted to Professor Alain Fischer before May 15 2014 Further information can be found at http://www.institutimagine.org/ OR email
Research Fellow in Gene Therapy for Lysosomal Diseases
Dr. Brian Bigger’s research group seeks a highly skilled, experienced and enthusiastic postdoctoral scientist joining. The applicant will drive a project to develop a novel gene therapy approach for Sanfilippo disease type B, using the labs international expertise in the development of therapies for lysosomal diseases. The applicant must have a strong background in either animal models of lysosomal storage disorders, glycobiology or gene therapy. Candidates with strong publication records and communication skills will be preferred. The applicant must be self-directed and thrive in an atmosphere that promotes independence and research leadership within a cohesive research group. The post offers the opportunity to work on an exciting project in a group with an established international reputation in stem cell and gene therapies. The position is funded by Action Medical Research. Informal enquiries can be made to Brian Bigger, Principal Investigator Email: brian.bigger@manchester.ac.uk. For further information visit the website. Closing date : 06/01/2014
1st Asia Pacific Inborn Errors of Metabolism course
Date: 09-11 January 2014
Venue: Tokyo, Japan
The 1st Asia Pacific Inborn Errors of Metabolism course is aimed at clinicians with a basic knowledge of inborn errors of metabolism who are training or working in this field. Both adult and childhood disease will be covered so it is suitable for practitioners in both areas. This course is intended to be interactive; it brings together a vast array of know-how, experts and resources to improve participants understanding of IEM in order to promote best practice in hospitals and healthcare systems For more information and to register (before November 20th), please visit www.orphan-europe-academy.com
European Cytogeneticists Association Courses
The European Advanced Postgraduate Course in Classical and Molecular Cytogenetics is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. Information for the 2014 course is now available. For Further details
5th ESO-SIOP Europe Masterclass in paediatric oncology
Date: 17-22 May 2014
Venue: Ljubljana, Slovenia
ESO and SIOP-Europe are pleased to announce the fifth Masterclass in Paediatric Oncology. This clinically-oriented educational programme has been designed for young paediatric oncologists who wish to improve their skills in clinical management of common childhood tumours. It is designed to offer a unique learning experience, providing practice-oriented training and the teaching sessions will focus on the application of the most recent research findings to clinical practice. Application deadline: 3rd February 2014. Information, detailed programme and application form available at www.eso.net
EUROPLAN National Conferences France
Date: 13 January 2014
Venue: Paris, France
Organised by Alliance Maladies Rares
For further details go to www.alliance-maladies-rares.org
EFGCP Annual Conference 2014 Benefits and Risks of Research:How Do We Redress the Current Imbalance?
Date: 28-29 January 2014
Venue: Brussels, Belgium
This conference will explore the consequences of research, both harm and benefit and look how we might achieve a fair balance that promotes improvements in health care, new medicines without diminishing protection of the research participant. It will also explore the current proposal for an EU Clinical Trial Regulation and its consequences. For Further information email or visit
EUROPLAN National Conferences Spain
Date: 24 January 2014
Venue: Burgos, Spain
Organised by FEDER; the Spanish Alliance for Rare Diseases
For further details go to www.enfermedades-raras.org
EUROPLAN National Conferences Ireland
Date: February 2014
Venue: Dublin, Ireland
Organised by GRDO, Genetic and Rare Disorders Organisation
For further details go to www.grdo.ie
EUROPLAN National Conferences Belgium
Date: 28 February 2014
Venue: Brussels, Belgium
Organised by Belgian National Alliance for Rare Diseases
For further details go to radiorg.be
RE(ACT) Congress: 2nd International congress on research of rare and orphan diseases
Date: 5-8March 2014
Venue: Basel, Switzerland
The conference sessions will explore issues and cutting-edge technologies that affect many adult and paediatric conditions. The following topics are to be discussed include Stem cell and cell therapy approaches, mapping diseases and genome instability, pathophysiology and diagnostics, bringing treatments to the clinic, degenerative disorders and research and patients.
For further information
The 9th International Congress on Autoimmunity
Date: 26-30 March 2014
Venue: Nice, France
This is a prominent conference with experts in immunology, rheumatology and related fields participating. The congress will address the genetic, etiology, diagnostic, clinical aspects and novel therapies of 80 autoimmune diseases.
For further details
2014 Lymphangioleiomyomatosis International Research Conference
Date: 28-30 March 2014
Venue: Chicago, USA
The LAM Foundation will be holding its 17 Annual International Lymphangioleiomyomatosis Research Conference and Patient & Family Educational Symposium on March 28 - 30 in Chicago, IL, USA. Save the date for this informative conference
For further details
7th European Conference on Rare Diseases & Orphan Products (ECRD 2014)
Date: 8-10 May 2014
Venue: Berlin, Germany
The European Conference on Rare Diseases & Orphan Products (ECRD) promises to be an enlightening forum for rare disease stakeholders across various disciplines across in European countries. It aims to cover research, development of new treatments, healthcare, social care, information, public health and support. For further details
13th International Congress on Neuromuscular Diseases - ICNMD 2014
Date: 5-11 July 2014
Venue: Marseille, France
The XIII ICNMD is a unique opportunity, where on a 4 years basis, experts come together to share knowledge and experiences in the field of neuromuscular diseases. Physicians and scientists, involved in the diagnosis and care to the most updated research in basic mechanisms and therapeutic approaches in the theme will greatly benefit. For further details
3rd International Conference on Immune Tolerance 2014
Date: 28th - 30th September 2014
Venue: Amsterdam, The Netherlands
The Third International Conference on Immune Tolerance will bring together international delegates to share their latest research and insights into the mechanisms and treatment of many conditions, most notably in transplantation, autoimmune diseases, inflammation and cancer.
For Further Information
14th International Congress on Neuronal Ceroid Lipofuscinoses (Batten Disease)
Date: 22-25 October 2014
Venue: Córdoba, Argentina
Batten disease is a common name for a group of rare, neurodegenerative genetic disorder affecting approximately 1 in 30,000 individuals. There is presently no known cure for Batten disease
Commercial events
2nd Orphan Drugs Research & Commercialization Conference
Date: 20-21 February 2014
Venue: San Diego, US
This meeting provides a forum for all stakeholders, from researchers, industry leaders, patient advocacy organizations, and regulatory experts to gather and share different perspectives on how to best guide the field forward. The program will include presentations on the latest scientific research, such as RNAi therapeutics and gene therapy; pricing and reimbursement challenges; clinical endpoints; and much more.
For Further Information
The World Orphan Drug Congress Asia 2014
Date: 10-11 June 2014
Venue: Singapore
The World Orphan Drug Congress Asia 2014 focuses on fostering partnerships and relationships between industry, governments, payers, investors and patients as well as to expedite orphan drug development and articulating its value, from discovery to clinical development, to license, to manufacturing, to launch and to sustainability of supply, so that manufacturers are guaranteed full and speedy reimbursement.
For Further Information