19 June 2015 print
Editorial
EU Policy News
Nat Pol News
ELS News
New Syndromes
New Genes
Research in Action
Patient Man & Therapy
Orphan Drugs
Grants
Partnersearch, Job Opps
Courses & Education
What's on?
Subscribe / Unsubscribe
Search the Orphanews archives :
Loading

Archives


 
Editorial
 
The launch of Rare Diseases International
 

The launch of Rare Disease International – a global voice for rare disease patients - was announced on 24 May, 2015 in Madrid, Spain. More than 60 patient representatives from 30 countries were present for the inauguration of Rare Diseases International (RDI) and to adopt a joint declaration to advocate for rare diseases as an international public health priority. RDI aims to represent rare disease patients and families from all over the world to provide a voice as well as visibility to rare diseases in the global health agenda.


RDI is a EURORDIS initiative, created in partnership with national alliances. The preliminary phase of the initiative is steered by EURORDIS and national rare disease alliances from the US (NORD), Canada (CORD), Japan (JPA), China (CORD), India (I-ORD), the Ibero-American pan-regional alliance (ALIBER) and the International Federation for Epidermolysis Bullosa (DEBRA International).

The main objectives of RDI are:
"-To promote rare diseases as an international public health and research priority by raising public awareness and influencing policy-making;
-To represent members and people living with a rare disease in international institutions such as the World Health Organisation and the United Nations Economic and Social Council; and
-To enhance the capacities of members to improve the lives of those living with or affected by a rare disease through information exchange, networking, mutual support and joint actions."


Along with advocating for rare diseases in international forums and multilateral institutions, they will also coordinate and participate in the International Rare Disease Research Consortium (IRDiRC). RDI will enhance partnerships and liase closely with Orphanet, International Alliance of Patients' Organizations (IAPO), International Conference on Rare Diseases & Orphan Drugs (ICORD), International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), International Federation of Human Genetics Societies (IFHGS).

“RDI creates a united global patient voice for all people living with a rare disease around the world, including those who don’t have a voice today, and works to turn ignorance, isolation and exclusion into knowledge, solidarity and hope,” says Yann Le Cam, Chief Executive Officer of EURORDIS, the European Organisation for Rare Diseases.
For further information
Photo courtesy: EURORDIS
 


 
EU Policy News
 
EGI InSPIRE efforts in marking the digital landscape in European Research Area
 
The EGI InSPIRE (Integrated Sustainable Pan-European Infrastructure for Researchers in Europe) project aimed to establish a sustainable European Grid Infrastructure (EGI) by bringing together National Grid Initiatives (NGIs) and other organisations across the EU. The project ran from May 2010 to December 2014, after which it was evaluated with the highest mark, by the European Commission (EC) review in February 2015. Originally, EGI InSPIRE dealt with the heavy computational requirements of big data users at CERN, the European Organisation for Nuclear Research, where physicists adopted the paradigm of distributed computing worldwide to solve their big data problems. But after its initial success, the model was considered to effectively serve "any pan European research community facing the problem of scalable access to large datasets." Through EGI InSPIRE, EGI offers users high throughput distributed data analysis by federating the computing, storage and data management capacity of 350 affiliated data centres and 21 cloud service providers worldwide. Currently the model has been widely replicated enough to be, in terms of geographic footprint, largest distributed computing infrastructure in the world.

The work of EGI InSPIRE will continue through EGI Engage, a project set up to accelerate the implementation of the Open Science Commons by expanding the capabilities of a European backbone of federated services for computing, storage, data, communication, knowledge and expertise, complementing community-specific capabilities.
For further information

 
Public Health Programme - Work Programme for 2015 European Commission
 
The European Commission has submitted the Work Programme for 2015 last week, which “sets out the priorities and actions to be undertaken, including the allocation of resources, to implement the third Programme of the Union’s action in the field of health (2014-2020) established under Regulation (EU) No 282/2014 (hereinafter referred to as ‘the Programme Regulation’) for the year 2015.”. A few projects towards helping rare disease patients have been included in this work programme.

The work programme has allocated €1,500,000 to establish methodologies for consensus guidelines on multi-disciplinary treatment on a selected pilot list of rare cancers which are complementary to the work developed by the FP7 RAREBESTPRACTICES project as well as with the European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment (ExPO-r-NeT). The funds will help towards formulating recommendations to introduce rare cancers into the National Cancer Plans and the National Rare Diseases Plans.

Additionally, €12,000,000 has been earmarked to support voluntary cooperation at scientific and technical level between Health Technology Assessment Bodies to validate the model for joint work to be continued after EU funding under the Health Programme. The work programme will also forward the agreement with the International Health Terminology Standards Development Organisation, which owns and administers the rights of SNOMED CT, to allow the use of this specific terminology within a cross-border context, and in specified EU projects, such as on rare diseases.

Ample assistance will also be provided to the development of a clinical trials database. The work programme will also support communication, promotion and dissemination of information on EU health policies and the results of the Health programmes.
Read the Work Programme

 
EMA
 
Public consultation on guidelines to aid developers of gene therapy through the regulatory process
 
Gene therapy holds great potential for the cure of many diseases, particularly in rare diseases and is an exiting and innovative field. However, bringing gene therapy to the market can be challenging as most of its developers are very small companies or come from academia, and are not familiar with the regulatory environment. The European Medicines Agency (EMA) has released a draft guideline on quality, nonclinical and clinical aspects of gene therapies for a three month public consultation. The draft guideline provides detailed guidance on both the scientific and development aspects of this type of medicines, and on the regulatory requirements that companies need to fulfill, including good manufacturing practice requirements.

According to the EMA "the draft guideline takes stock of the experience gained with gene therapies in recent years through scientific advice, the classification of advanced therapies and marketing authorisation applications, and addresses issues observed during these procedures."

Stakeholders can send their comments on this draft guideline to advancedtherapies@ema.europa.eu by 31 August 2015 using the form provided.
Read the Draft guidelines by the EMA

 


 
National & International Policy Developments
 
Other European news
 
Work of Telethon Research Institutes TIGEM and TIGET in Italy
 
An article published in Human Gene Therapy reviews the two telethon research institutes in Italy: Telethon Institute of Genetics and Medicine (TIGEM) and the San Raffaele Telethon Institute for Gene Therapy (TIGET). The article describes TIGEM as a "multidisciplinary research institute devoted to the study of the genetic defects and the mechanisms of genetic diseases, and to the development of safe and effective therapies." Research at TIGEM is focused on three strategic programs: Cell Biology of Genetic Diseases, Systems Biology and Functional Genomics, and Molecular Therapy. The review describes their many achievements in vivo vector-mediated gene delivery, one of them being the first clinical trials of gene therapy for a genetic form of blindness. They also describe important alliances with pharmaceutical companies such as Shire PLC established in 2012 to further translational research in rare diseases.

The authors describe TIGET as a "joint venture between the Telethon Foundation and the San Raffaele Scientific Institute in Milan, with the mission to perform cutting edge research on gene transfer and cell and gene therapy, and to promote its translation into therapeutic advances for genetic diseases." The article reviews TIGETs’ pioneering work in the gene therapy of a severe form of primary immunodeficiency (ADA-SCID), developing a hematopoietic stem cell (HSC) – based gene therapy employing gamma-retroviral vectors. Also reported in the article is TIGETs' strategic alliance with GlaxoSmithKline (GSK) for the clinical development of HSC-based gene therapy for some rare diseases that, according to the authors, are committed to develop ADA-SCID gene therapy toward registration and marketing.
Access the article

 
The French national minimum data set for rare diseases registries
 
The second French National Plan for Rare Diseases highlighted the necessity for better care coordination and epidemiology to find necessary expertise for the diagnosis and care as well as for determining the patient numbers needed for rare disease research. The plan proposed standardisation of clinical data in order to normalise and facilitate exchange of rare disease patient data which led to building the French national minimum set (F-MDS-RD).

An article published in the Journal of the American Medical Informatics Association describes the development of F-MDS-RD common to 131 expert rare disease centres. After identifying 4 national expert group and extensive literature review, the authors created the 1st versions of F-MDS-RD, which was then validated by the French rare disease centres and the National Plan strategic committee. Its current composition includes 58 data elements and it is HL7 compatible to use with various ontologies and it is aligned with other common data elements initiatives. According to the authors F-MDS-RD “can foster better care coordination and facilitate determining rare disease patients’ eligibility for research studies, trials, or cohorts. Since other countries will need to develop their own standards for rare disease data collection, they might benefit from the methods presented here.”
Read the PubMed abstract

 
Report on the first year of implementation of the crossborder healthcare initiative
 

As part of the deliverables for Directive 2011/24/EU on the application of patients’ rights in cross-border healthcare, a report analysing the functioning of the Directive was published. The analysis was conducted by means of a number of evaluative questions addressing reimbursement, quality and safety of cross border healthcare and undue delay. The questions were addressed to stakeholders in 12 countries with a certain level of existing cross-border activity. The study also included a pseudo patient investigation exercise to understand the operational functioning of the Directive as well as the critical role of National contact points.

According to the report, although cross-border Healthcare is moving at a fast pace, there is still a lag in its usage as the number of patients utilising its benefits is still very low. While the report considered its findings limited in scope - there are no specifics provided in terms of rare disease patients – the Commission contends that it is because the Directive is still in its early stages of implementation. However, the report recommends “more targeted and regular publicity and communication activities” so as to inform on citizens rights as well as the specific steps required to avails the services provided by the cross-border initiatives.
Read the report

 
Phenylketonuria screening and management in southeastern Europe – survey results from 11 countries
 
An article published in Orphanet Journal of Rare Diseases assessed the current state of Phenylketonuria (PKU) screening and management in the region of southeastern Europe. The authors surveyed professionals responsible for the PKU management in the 11 countries from the southeastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The authors found that while National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry and patient’s PKU society existed in 7 of 11 countries, PKU screening was not yet introduced in 4 of 11 countries and routine genetic diagnostics was reported only in 4 of 11 countries. Furthermore, the most commonly used laboratory method to assess phenylalanine levels was fluorometric and tetrahydrobiopterine was used in only 2 of 11 countries. They also reported that paediatricians cared for these patients while a dietician was a member of PKU team in only 4 of 11 countries. The authors concluded that the management of PKU in southeastern Europe is falling behind internationally established standards-of care in many aspects and as an immediate measure neonatal screening should be introduced throughout the region.
Read the open access article

 
Other International News
 
Australian state Victoria plans a genomic sequencing programme in its budget
 
The 2015-16 Victorian Budget in Victoria, Australia has earmarked AUD 25 million to develop a state-wide genomic sequencing programme. The funding has been allocated to the Melbourne Genomics Health Alliance which comprises of the Royal Melbourne Hospital, Royal Children’s Hospital, University of Melbourne, Walter and Eliza Hall Institute, Murdoch Children’s Research Institute, CSIRO and Australian Genome Research Facility. The Alliance will ensure that up to 2500 children and adults receive early diagnoses of their conditions. Stakeholders of the rare disease community believe that this will speed up the diagnosis and treatment of rare conditions and inherited diseases in Victoria, Australia. It will also mean Victorians with hereditary diseases will have greater understanding about how their genetic condition might impact them and their families in the future and the knowledge gained from this exercise will be applied across the health system.
Read the press release by the Premier of Victoria, Australia

 
Heartbreaking story of family in India compelled to ask euthanasia for children with rare disease
 
An Indian father has shared a poignant story of his struggle to provide for his 6 children who are suffering from a rare genetic disorder – Canavan disease. This degenerative condition gradually paralyses the body, leading to seizures as well as vision and hearing loss, and has resulted in 6 of his children in need of constant medical attention. The family lives below the poverty line and is unable to provide the required care to their children, which has led the father Mohd Nazir to plead the President of India to allow 6 of his children to be euthanized. Mr Nazir’s request for mercy killing does not fall under the Indian Supreme Court's guidelines for regulated passive euthanasia which allows withdrawal of life-prolonging medical treatment for the terminally ill patients. However, the parents see euthanasia as their only option as they lack the means to look after the children and are heartbroken to watch their children suffer as their condition deteriorate.

Although, in this case the President has promised funds to help the family, possibly due to the media attention, this is the heartrending story of many families in India with rare disease patients.
For further information

 
Maple syrup urine disease in Brazil characterised by late diagnosis and lack of treatment
 
An article published in Jornal de Pediatria (in Portuguese) has characterised a sample of Brazilian patients with maple syrup urine disease (MSUD) diagnosed between 1992 and 2011. The patients were identified through a national reference laboratory for the diagnosis of MSUD and through contact with other medical genetics services across Brazil. The authors found that early diagnosis is associated with the presence of positive family history and decreased prevalence of clinical manifestations at the time of diagnosis, but not with a better outcome. The authors conclude that patients with MSUD in Brazil are usually diagnosed late and exhibit neurological involvement, poor survival despite obtaining early diagnosis. The authors suggest development of better public policies for diagnosis and treatment of MSUD.
Article in Portuguese
Read the PubMed abstract

 
Guidance Documents and Recommendations
 
Eosinophilic granulomatosis with polyangiitis: consensus task force recommendations for evaluation and management
 
Read the Pubmed abstract
 
To read more about "Eosinophilic granulomatosis with polyangiitis"

 
Eur J Intern Med. ; [Epub ahead of print] ; May 2015
 
Bioinformatics, Registries and Data Management
 
A framework to integrate heterogeneous clinical data into a central registry
 
An article published in e-Health – For Continuity of Care describes a framework to integrate heterogeneous clinical data into a central repository which has been noted as necessary for clinical research. The authors state that it is especially crucial for rare disease research as it is often necessary to “aggregate study data from several sites in order to achieve a statistically significant cohort size.” The authors describe a best practice framework that consists of three sequential steps which involves “(1) creating a harmonisation table, (2) setting up an ETL process and finally (3) putting the resulting data structure into a central repository that enables custom queries.” To decrease the work load and improve the understanding of the complexity behind data integration, they provide spreadsheets and ETL templates to support an individual implementation. Integrating heterogeneous clinical data into a central data repository is considered a necessary step for clinical research.
Read the open access article

 
Protein-protein interaction disturbances by missense genetic variants is a very good predictor of disease severity
 
A study published in Cell uses high-throughput functional assays for an extensive characterisation of the effects of disease-associated missense genetic variants, which result in amino acid substitutions in the encoded proteins. They categorised the mutations according to the extent to which they abolished protein–protein interactions (PPIs). They were classified as ‘quasi-null’ when they terminated all interactions, ‘edgetic’ when a subset of specific interactions were abolished, and ‘quasi-wild-type’ when none of interactions were apparently affected. They found that most of the disease-associated mutations that had functional consequences on PPIs and were either edgetic or quasi-null in contrast to the normal human variation, which were largely quasi-wild-type. Thus the authors believe that “this interaction profiling could be a useful tool to distinguish benign from disease-causal variants.”

The authors stated that "this functional analyses performed favourably compared with purely computational predictors of variant deleteriousness, and the number of PPIs disrupted by the mutations correlated positively with disease severity." Overall, the authors believe that their study offers a worthwhile strategy to investigate the functional consequences of disease-associated genetic variants.
Read the PubMed abstract

 
Factors influencing success of clinical genome sequencing across a broad spectrum of disorders
 
An article published in Nature Genetics assessed factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis. The authors sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. They quantified the number of candidate variants identified using different strategies for "variant calling, filtering, annotation and prioritisation and found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy." Overall, the authors identified “disease-causing variants in 21% of cases, with the proportion increasing to 34% for mendelian disorders and 57% in family trios. They also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable.”
Read the PubMed abstract

 
ClinGen — The clinical genome resource of the National Institute of Health in the United States
 
A detailed review of ClinGen is presented in New England Journal of Medicine, which was launched in 2013 and supported by the National Institutes of Health, to be an "authoritative central resource that defines the clinical relevance of genomic variants for use in precision medicine and research." The review addresses the goals of the Clinical Genome Resource (ClinGen) and discusses how the ClinVar database - the cornerstone of ClinGen - operates. The article describes ClinVar as the public portal for the deposition and retrieval of variants and the interpretation of their clinical significance. It currently contains 172,055 variant submissions across 22,864 genes out of which more than 118,000 of the unique variants in ClinVar have clinical interpretations. The authors maintain that ClinVar ensures that all variants are recorded according to standardised nomenclature and works with members of the sequence and structural variant communities to develop new standards for interpreting genetic variants.

Additionally, the authors also illustrate the work of the ClinGen Gene Curation Working Group towards developing standards for assigning the level of evidence supporting a gene–disease relationship and a new database called ClinGenKB, which allows for a flexible working environment for curation. Finally, the authors highlight the activities of ClinGen Actionability Working Group and GenomeConnect.
Access the article

 
Screening and Testing
 
FDA role in genomic tests: postmarketing surveillance trumps premarket review
 
The Food and Drug Administration (FDA) recently advanced two draft guidances proposing a regulatory framework for laboratory-developed tests, which includes many genomic tests. This has kindled debate on whether the FDA can regulate genomic testing well. The authors of an opinion piece published in the New England Journal of Medicine have stated their support for postmarketing surveillance rather than a premarket review. The authors believe that FDA does not have the structural capacity to avail pre-existing data resources for genetic tests due the large amount of data that is available. They also state that FDA premarket approval process for genomic tests cannot ensure consumer safety because the clinical trials are "too small, brief, and unrepresentative of real patient contexts." Additionally, they believe that premarket review cannot ensure clinical validity for every variant as the full range of variants becomes clear only after the test is widely used. They believe that the consequent costs and delays caused by premarket reviews would deter many laboratories in the United States.

The authors emphasise that establishing the clinical validity of genomic tests is largely a postmarketing pursuit as it requires the accrual and review of evidence throughout the entire commercial life of a test and from other tests involving similar regions of the human genome. Finally the authors believe that “statutory reforms should focus on granting the FDA a correct package of legal powers, seed funding, and legal pathways to encourage public–private partnerships to develop and sustain data resources for the right regulation of genomic testing.”
Access the article

 


 
Ethical, Legal & Social Issues
 
Recommendations to communicate the promise of ocular gene therapy
 
An article published in American Journal of Ophthalmology has identified challenges and recommends solutions for communicating details on ocular gene therapy between patients and clinicians as clinical research progresses. The authors performed a literature review of science communication best practices to inform recommendations for patient-clinician discussions about ocular gene therapy. The authors stress that although ocular gene therapy clinical trials are raising the hopes of many patients, the work is still in its nascent stage and currently the clinical trials are still experimental involving some risks.

They recommend that clinicians should assist patients by providing "realistic estimates for lengthy clinical development timelines and positioning current research within models of clinical translation." which will help them understand their therapeutics alternatives. The authors contend that “clinicians should be prepared to counter overly-optimistic messaging, especially that found in news media and the Internet, with optimism tempered by evidence and that such communications will become increasingly important as novel gene and cell therapies advance through clinical development and will support the ethical translation of these fields.”
Read the PubMed abstract

 
Rare Genomics Institute announces initiative to study benefits of crowdfunding to help patients access DNA sequencing
 
The Rare Genomics Institute, an international non-profit organisation has announced the Amplify Hope Initiative, a new study aimed at determining how crowdfunding can promote scientific research to help rare disease patients. Supported by a grant from the Templeton Foundation, the project aims to measure the effectiveness of different crowdfunding strategies to understand the scientific impact and community engagement in such strategies.

Rare Genomics Institute is inviting patients in need of genetic sequencing to join the Amplify Hope Initiative. Approximately 50 families will be randomly assigned to a crowdfunding strategy and platform to raise money for their DNA sequencing. The organisation will assist patients in implementing different crowdfunding strategies and methods, and track the overall reach and scientific impact of such strategies and methods.

Participants and donors of these crowdfunding efforts will be asked to complete surveys to enable the Institute to create additional resources, support, and education tailored to rare disease patients and caregivers. Study participants have started recruiting since May this year. To participate, complete the application form. Participants will be assigned to a crowdfunding strategy and platform to raise money for their sequencing.

For further information

 
Crowdsourcing project to speed research on rare genetic disorder
 
An article published in Science Magazine describes the launch of a crowdsourcing curation campaign, dubbed Mark2Cure by harnessing the efforts of lay volunteers who will scan papers for key terms to help create a powerful searchable database. A team of scientists at Scripps Research Institute in San Diego, California aims to engage lay people for a curation project for diseases. The researchers have pointed to a study conducted in the Scripps which found that "although the average novice doesn’t curate as well as a person with a doctorate, groups of novices actually perform on par, or even slightly better, than a professional." The project aims to build a knowledge base that requires humans to teach computers key concepts from curated articles. According to the researchers "anyone with modest online training, anyone who reads English can scan research papers for key terms—names of genes, proteins, diseases, and drugs—and use online marking tools to document relationships between them." It is first reaching out to the community of people affected by NGLY1 deficiency, a newly discovered genetic disorder, caused by defects in NGLY1, an enzyme that removes sugar molecules from proteins to ensure proper degradation. They will then ask other volunteers to perform these tasks on their own time at home.
 
A study on attitudes towards returning raw sequence data to patients
 
An article published in Journal of Medical Genetics illustrates the ethics and responsibility of researchers on returning raw genome sequencing data to patients. The authors state that health-related results discovered while conducting research on the genome should only be returned to the research participant "after being clinically validated and then delivered and followed up within a health service." However, they also understand that returning such results may be difficult for researchers limited by resources or access to appropriate clinicians but are able to return raw sequence data. The authors explore attitudes of over 7000 members of the public, genomic researchers, genetic health professionals and non-genetic health professionals and ask participants to suggest what they would do with a raw sequence, if offered. They found that 62% participants were interested in using it to seek out their own clinical interpretation and theredore suggest that returning this data should be made feasible in the future. The authors do not conclude that “sharing raw genomic data from sequencing research is necessarily the correct way forward at this point, particularly given the current interpretive uncertainties.” However, the authors believe that there needs to be a thorough scientific and ethical debate in order to create a moral framework that will guide policy towards returning raw sequence data.
Read the PubMed abstract

 


 
New Syndromes
 

 
A novel form of autosomal dominant spastic paraplegia associated with a mutation in CPT1C
 
The authors identified a novel form of autosomal dominant spastic paraplegia that they termed ‘hereditary spastic paraplegia type 73’. Whole-exome sequencing was performed, and a mutation was found in CPT1C.
Consult the Pubmed abstract

 
JAMA Neurol. ; 72(5):561-70 ; May 2015
 
Hereditary autoimmune-mediated lung disease and arthritis caused by COPA mutations in five families
 
The authors performed whole-exome sequencing and targeted sequencing in five families with an apparent undescribed mendelian syndrome of autoimmunity characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease. They identified four unique deleterious variants in the COPA gene.
Consult the Pubmed abstract

 
Nat Genet. ; 47(6):654-60 ; June 2015
 
Eye-intellectual disability syndrome due to homozygous MED25 mutation in four unrelated families
 
The authors performed exome sequencing in seven patients from four unrelated families, all originating from the same village, with a syndrome characterized by eye, brain, cardiac and palatal abnormalities as well as growth retardation, microcephaly and severe intellectual disability. They identified a homozygous mutation in the MED25 gene.
Consult the Pubmed abstract

 
Hum Genet. ; 134(6):577-87 ; June 2015
 
Thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia associated with germline mutations in ETV6
 
The authors identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume and two occurrences of B cell-precursor acute lymphoblastic leukemia. Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations.
Consult the Pubmed abstract

 
Nat Genet. ; 47(5):535-8 ; May 2015
 


 
New Genes
 

 
Zimmermann-Laband syndrome caused by mutations in KCNH1 and ATP6V1B2
 
Consult the Pubmed abstract
 
To read more about "Zimmermann-Laband syndrome"

 
Nat Genet. ; 47(6):661-7 ; June 2015
 
Autosomal-recessive Huntington-like disorder due to RNF216 mutations in two Belgian families
 
Consult the Pubmed abstract
 
Neurology ; 84(17):1760-6 ; April 2015
 
Pontocerebellar hypoplasia type 3 associated with a homozygous nonsense PCLO mutation in two affected individuals
 
Consult the Pubmed abstract
 
To read more about "Pontocerebellar hypoplasia type 3"

 
Neurology ; 84(17):1745-50 ; April 2015
 
Familial amyotrophic lateral sclerosis and fronto-temporal dementia caused by haploinsufficiency of TBK1
 
Consult the Pubmed abstract
 
To read more about "Frontotemporal dementia with motor neuron disease"

 
Nat Neurosci. ; 18(5):631-6 ; May 2015
 
Primary familial brain calcification due to mutations in XPR1
 
Consult the Pubmed abstract
 
To read more about "Bilateral striopallidodentate calcinosis"

 
Nat Genet. ; 47(6):579-81 ; June 2015
 
Chronic mucocutaneous candidosis linked to IL-17RC deficiency in three patients
 
Consult the Pubmed abstract
 
To read more about "Chronic mucocutaneous candidosis"

 
J Exp Med. ; 212(5):619-31 ; May 2015
 
Autoinflammation, immunodeficiency, amylopectinosis and lymphangiectasia associated with HOIP deficiency in one patient
 
Consult the Pubmed abstract
 
To read more about "Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis"

 
J Exp Med. ; 212(6):939-51 ; June 2015
 
Brachydactyly - arterial hypertension caused by PDE3A missense mutations in six unrelated families
 
Consult the Pubmed abstract
 
To read more about "Brachydactyly - arterial hypertension"

 
Nat Genet. ; 47(6):647-53 ; June 2015
 
West syndrome: NR2F1 as a causative gene, and CACNA2D1 and BRWD3 as candidate genes
 
Consult the Pubmed abstract
 
To read more about "West syndrome"

 
Hum Genet. ; 134(6):649-58 ; June 2015
 
Myasthenia gravis: CTLA4, HLA-DQA1 and TNFRSF11A as susceptibility genes
 
Consult the Pubmed abstract
 
To read more about "Myasthenia gravis"

 
JAMA Neurol. ; 72(4):396-404 ; April 2015
 
A homozygous loss-of-function germline mutation in the NTHL1 gene predisposes to adenomatous polyposis and colorectal cancer
 
Consult the Pubmed abstract
 
To read more about "Familial adenomatous polyposis"

 
Nat Genet. ; 47(6):668-71 ; June 2015
 


 
Research in Action
 

 
Clinical Research
 
POEMS syndrome: autologous stem cell transplantation improves neuropathy, however, fatal complications can occur
 
Consult the Pubmed abstract
 
To read more about "POEMS syndrome"

 
Neurology ; 84(19):1981-7 ; May 2015
 
Gaucher disease type 1: lowering imiglucerase dose has less impact on the patients’ outcomes than interrupting treatment
 
Consult the Pubmed abstract
 
To read more about "Gaucher disease type 1"

 
Orphanet J Rare Dis. ; 10:62 ; May 2015
 
Niemann-Pick disease type C: stable or improved neurological manifestations during miglustat therapy
 
Consult the Pubmed abstract
 
To read more about "Niemann-Pick disease type C"

 
Orphanet J Rare Dis. ; 10(1):65 ; May 2015
 
Duchenne muscular dystrophy: idebenone reduces the loss of respiratory function and represents a new treatment option
 
Consult the Pubmed abstract
Consult this study on Orphanet
Consult this study on Orphanet
Consult this study on Orphanet

 
To read more about "Duchenne muscular dystrophy"

 
Lancet ; 385(9979):1748-57 ; May 2015
 
Normal pressure hydrocephalus: lumboperitoneal shunt surgery might be beneficial and could be a first-line treatment option
 
Consult the Pubmed abstract
 
Lancet Neurol. ; 14(6):585-94 ; June 2015
 
Homozygous familial hypercholesterolemia: infusions of CER-001, a recombinant human apolipoprotein, result in reduction in carotid mean vessel wall area
 
Consult the Pubmed abstract
 
To read more about "Homozygous familial hypercholesterolemia"

 
Am Heart J. ; 169(5):736-742 ; May 2015
 
Von Hippel-Lindau disease: sunitinib may achieve a good disease control in patients with renal cell carcinoma
 
Consult the Pubmed abstract
 
To read more about "Von Hippel-Lindau disease"

 
Fam Cancer. ; 14(2):309-16 ; June 2015
 
Glioblastoma: temozolomide monotherapy may have greater benefit than radiotherapy in elderly patients with MGMT promoter methylation
 
Consult the Pubmed abstract
 
To read more about "Glioblastoma"

 
JAMA Neurol. ; 72(5):589-96 ; May 2015
 
Chronic lymphocytic leukemia: ibrutinib controls disease manifestations and is well tolerated for an extended period
 
Consult the Pubmed abstract
 
To read more about "B-cell chronic lymphocytic leukemia"

 
Blood ; 125(16):2497-506 ; April 2015
 
Chronic lymphocytic leukemia: addition of ofatumumab to chlorambucil leads to clinically important improvements with a manageable side-effect profile
 
Consult the Pubmed abstract
Consult this study on Orphanet
Consult this study on Orphanet
Consult this study on Orphanet

 
To read more about "B-cell chronic lymphocytic leukemia"

 
Lancet ; 385(9980):1873-83 ; May 2015
 
Diffuse large B-cell lymphoma: weekly rituximab consolidation following four cycles of R-CHOP21 results in an acceptable response with high tolerability
 
Consult the Pubmed abstract
 
To read more about "Diffuse large B-cell lymphoma"

 
Eur J Haematol. ; 94(6):504-10 ; June 2015
 
Hodgkin lymphoma: brentuximab vedotin after autologous stem cell transplantation improves progression-free survival
 
Consult the Pubmed abstract
Consult this study on Orphanet

 
To read more about "Hodgkin lymphoma"

 
Lancet ; 385(9980):1853-62 ; May 2015
 
Treatment with pazopanib is associated with tumour response for patients with pancreatic neuroendocrine tumours but not for patients with carcinoid tumours
 
Consult the Pubmed abstract
 
To read more about "Endocrine tumor"
To read more about "Pancreatic endocrine tumor"

 
Lancet Oncol. ; [Epub ahead of print] ; May 2015
 
Gastrointestinal stromal tumor: nilotinib cannot be recommended for broad use as a first-line treatment
 
Consult the Pubmed abstract
Consult this study on Orphanet

 
To read more about "Gastrointestinal stromal tumor"

 
Advanced soft-tissue sarcoma: mitigated results with the combination of ombrabulin and cisplatin
 
Consult the Pubmed abstract
 
Lancet Oncol. ; 16(5):531-40 ; May 2015
 
Chronic graft versus host disease: National Institutes of Health consensus development project on criteria for clinical trials
 
Consult the Pubmed abstract
 
To read more about "Chronic graft versus host disease"

 
Biol Blood Marrow Transplant. ; [Epub ahead of print] ; May 2015
 
Therapeutic Approaches
 

 
Hemophilia: ALN-AT3, an RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in mice and nonhuman primates
 
Consult the Pubmed abstract
 
To read more about "Hemophilia"

 
Nat Med. ; 21(5):492-7 ; May 2015
 
Gaucher disease type 1: lentiviral gene therapy using cellular promoters cures the disease in mice
 
Consult the Pubmed abstract
 
To read more about "Gaucher disease type 1"

 
Mol Ther. ; 23(5):835-44 ; May 2015
 
X-linked adrenoleukodystrophy: adeno-associated virus serotype 9-mediated gene therapy reduces very long-chain fatty acids in mouse brain and spinal cord
 
Consult the Pubmed abstract
 
To read more about "X-linked adrenoleukodystrophy"

 
Mol Ther. ; 23(5):824-34 ; May 2015
 
Recessive dystrophic epidermolysis bullosa: rescue of the mucocutaneous manifestations by human cord blood derived non-hematopoietic stem cells in a mouse model
 
Consult the Pubmed abstract
 
Stem Cells ; 33(6):1807-17 ; June 2015
 
Diagnostic Approaches
 

 
Treatable intellectual developmental disabilities: retrospective analysis supports algorithm as efficient diagnostic approach
 
Consult the Pubmed abstract
 
Mol Genet Metab. ; 115(1):1-9 ; May 2015
 
Von Willebrand disease: laboratory diagnosis
 
Consult the Pubmed abstract
 
To read more about "Von Willebrand disease"

 
Int J Lab Hematol. ; 37 Suppl 1:11-7 ; May 2015
 
The clinical and laboratory evaluation of the patient with erythrocytosis
 
Consult the Pubmed abstract
 
To read more about "Polycythemia vera"

 
Eur J Intern Med. ; 26(5):297-302 ; June 2015
 
Rhabdomyolysis: diagnostic evaluation and genetic perspective
 
Consult the Pubmed abstracts
 
Muscle Nerve ; 51(6):793-810 ; June 2015
Orphanet J Rare Dis. ; 10(1):51 ; May 2015

 
Neuroferritinopathy: description of a distinct imaging pattern of cortical iron deposition on susceptibility-weighted MRI as a diagnostic clue
 
Consult the Pubmed abstract
 
To read more about "Neuroferritinopathy"

 
Neurology ; 84(17):1816-8 ; April 2015
 
Inclusion body myositis: myositis with endomysial cell invasion as a diagnostic clue, even if other criteria are not fulfilled
 
Consult the Pubmed abstract
 
To read more about "Inclusion body myositis"

 
Neuromuscul Disord. ; 25(6):451-6 ; June 2015
 
Inflammatory nerve disorders: diagnostic utility of auto antibodies
 
Consult the abstract
 
Journal of Neuromuscular Diseases ; 2(2):107-112 ; 2015
 
Near-infrared spectroscopy differentiates samples of dermatomyositis and inclusion-body myositis from controls, but cannot distinguish polymyositis samples from controls
 
Consult the Pubmed abstract
 
To read more about "Polymyositis"
To read more about "Dermatomyositis"
To read more about "Inclusion body myositis"

 
Muscle Nerve ; 51(6):830-7 ; June 2015
 


 
Patient Management and Therapy
 
Long-chain fatty acid oxidation disorders: review on orphan drugs in development
 
Consult the abstract
 
Orphan Drugs: Research and Reviews ; Volume 5:33-41;2015 ; 2015
 
Sickle cell anemia: review on prevention and management of the infection
 
Consult the Pubmed abstract
 
To read more about "Sickle cell anemia"

 
Br J Haematol. ; [Epub ahead of print] ; May 2015
 
Sickle cell anemia: Cochrane review on phytomedicines
 
Consult the Pubmed abstract
 
To read more about "Sickle cell anemia"

 
Cochrane Database Syst Rev. ; 4:CD004448 ; April 2015
 
Cystic fibrosis: Cochrane review on enteral tube feeding
 
Consult the Pubmed abstract
 
To read more about "Cystic fibrosis"

 
Cochrane Database Syst Rev. ; 4:CD001198 ; April 2015
 
Cystic fibrosis: Cochrane review on recombinant growth hormone therapy
 
Consult the Pubmed abstract
 
To read more about "Cystic fibrosis"

 
Cochrane Database Syst Rev. ; 5:CD008901 ; May 2015
 
Fragile X syndrome: Cochrane review on L-acetylcarnitine for the treatment
 
Consult the Pubmed abstract
 
To read more about "Fragile X syndrome"

 
Cochrane Database Syst Rev. ; 5:CD010012 ; May 2015
 
Mastocytosis: review on current treatment options
 
Read the Pubmed abstract
 
Eur J Haematol. ; 94(6):474-90 ; June 2015
 
Epidermolysis bullosa: review on novel gene and cell therapies
 
Read the Pubmed abstract
 
Mol Ther. ; 23(6):987-992 ; June 2015
 
Anti-neutrophil cytoplasmic antibody-associated vasculitis: three reviews on therapies
 
Consult the Pubmed abstracts
 
To read more about "Anti-neutrophil cytoplasmic antibody-associated vasculitis"

 
Presse Med. ; 22, 25, 29, ; May 2015
 
Hereditary spherocytosis: pediatrician practical guide on diagnosis and treatment
 
Consult the Pubmed abstract
 
To read more about "Hereditary spherocytosis"

 
Pediatrics ; [Epub ahead of print] ; May 2015
 
Membranous nephropathy: review on pathophysiological advances
 
Consult the abstract
 
The Lancet ; Volume 385(9981):1983–1992 ; May 2015
 
Primary familial brain calcification: a review
 
Consult the Pubmed abstract
 
To read more about "Bilateral striopallidodentate calcinosis"

 
JAMA Neurol. ; 72(4):460-7 ; April 2015
 
Hereditary spastic paraplegia: a review
 
Consult the Pubmed abstract
 
To read more about "Hereditary spastic paraplegia"

 
Hum Genet. ; 134(6):511-38 ; June 2015
 
Chylomicronaemia: review on diagnosis and therapies
 
Consult the Pubmed abstract
 
Nat Rev Endocrinol. ; 11(6):352-362 ; June 2015
 
Rett syndrome: a review
 
Consult the Pubmed abstract
 
To read more about "Rett syndrome"

 
Nat Rev Genet. ; 16(5):261-75 ; May 2015
 
Erdheim-Chester disease: a review
 
Consult the Pubmed abstract
 
To read more about "Erdheim-Chester disease"

 
Eur J Intern Med. ; 26(4):223-229 ; May 2015
 
Cryopyrin-associated periodic syndrome: a review
 
Consult the Pubmed abstract
 
To read more about "Cryopyrin-associated periodic syndrome"

 
Semin Immunopathol. ; [Epub ahead of print] ; May 2015
 
Paroxysmal nocturnal hemoglobinuria: a review
 
Consult the Pubmed abstract
 
To read more about "Paroxysmal nocturnal hemoglobinuria"

 
Eur J Haematol. ; 94(6):464-73 ; June 2015
 
Achalasia: a review
 
Consult the Pubmed abstract
 
To read more about "Idiopathic achalasia"

 
JAMA ; 313(18):1841-52 ; May 2015
 
Autoimmune congenital heart block: a review
 
Consult the Pubmed abstract
 
Nat Rev Rheumatol. ; 11(5):301-312 ; May 2015
 
Hepatoportal sclerosis: a review
 
Consult the Pubmed abstract
 
To read more about "Hepatoportal sclerosis"

 
Orphanet J Rare Dis. ; 10(1):67 ; May 2015
 
Pulmonary Langerhans cell histiocytosis: a review
 
Consult the Pubmed abstract
 
To read more about "Adult pulmonary Langerhans cell histiocytosis"

 
Eur J Intern Med. ; 26(5):351-6 ; June 2015
 
Multicentric reticulohistiocytosis: a critical review
 
Consult the Pubmed abstract
 
To read more about "Multicentric reticulohistiocytosis"

 
Curr Rheumatol Rep. ; 17(6):511 ; June 2015
 
Paediatric rheumatic diseases: review on advances in biomarkers
 
Consult the Pubmed abstract
 
Nat Rev Rheumatol. ; 11(5):265-275 ; May 2015
 
Juvenile idiopathic arthritis: review on the management
 
Consult the Pubmed abstract
 
To read more about "Juvenile idiopathic arthritis"

 
Nat Rev Rheumatol. ; 11(5):290-300 ; May 2015
 
Uveitis associated with juvenile idiopathic arthritis: a review
 
Consult the Pubmed abstract
 
To read more about "Juvenile idiopathic arthritis"

 
Nat Rev Rheumatol. ; 11(6):338-348 ; June 2015
 
Vernal keratoconjunctivitis: review with emphasis on proteomics
 
Consult the Pubmed abstract
 
To read more about "Vernal keratoconjunctivitis"

 
Life Sci. ; 128:47-54 ; May 2015
 
Childhood brain tumours: review on genetic and targeted therapies
 
Consult the abstract
 
The Lancet Oncology ; 16(6):e293-e302 ; June 2015
 
Advanced lung neuroendocrine tumour: review on management
 
Consult the Pubmed abstract
 
To read more about "Bronchial endocrine tumor"

 
J Thorac Dis. ; 7(Suppl 2):S163-71 ; April 2015
 
Primary hepatic angiosarcoma: a review
 
Consult the Pubmed abstract
 
To read more about "Angiosarcoma"

 
Eur J Surg Oncol. ; [Epub ahead of print] ; May 2015
 
Oncogenic osteomalacia: a review
 
Consult the Pubmed abstract
 
To read more about "Oncogenic osteomalacia"

 
Curr Rheumatol Rep. ; 17(6):512 ; June 2015
 
Desmoid tumour: a review
 
Consult the Pubmed abstract
 
To read more about "Desmoid tumor"

 
Fam Cancer. ; 14(2):211-9 ; June 2015
 
Multiple myeloma: a review
 
Consult the Pubmed abstract
 
To read more about "Multiple myeloma"

 
Lancet ; [Epub ahead of print] ; December 2014
 
Acute lymphoblastic leukemia: review on genomics
 
Consult the Pubmed abstract
 
To read more about "Acute lymphoblastic leukemia"

 
Nat Rev Clin Oncol. ; 12(6):344-357 ; June 2015
 
Special issue of ‘Clinical Genetics’ on Lynch syndrome
 
Consult the special issue
 
To read more about "Hereditary nonpolyposis colon cancer"

 
Clinical Genetics ; Volume 87, Issue 6, Pages 503-603 ; June 2015
 
Special issue of ‘Infectious Disease Clinics of North America’ on Lyme disease and babesiosis
 
Consult the special issue
 
To read more about "Lyme disease"
To read more about "Babesiosis"

 
Infectious Disease Clinics of North America ; Volume 29, Issue 2, Pages 187-390 ; June 2015
 
Six updated GeneReviews published
 
GeneReviews are expert-authored, peer-reviewed disease descriptions ("chapters") presented in a standardized format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions. Six updated GeneReviews have been published for:
Angelman syndrome
Beta-thalassemia
Familial hemiplegic migraine
Noonan syndrome with multiple lentigines
Kleefstra syndrome
Non-syndromic 46, XX testicular disorders of sex development

 


 
Orphan Drugs
 
Regulatory News
 

 
Unituxin recommended by EMA for the treatment of neuroblastoma in children
 
The European Medicines Agency (EMA) has recommended granting a marketing authorisation for Unituxin (dinutuximab) for the treatment of high-risk neuroblastoma, a rare cancer forming from immature nerve cells that most often found in young children. Unituxin is to be used in children who have responded to an induction treatment with chemotherapy, followed by myeloablative therapy and autologous stem cell transplantation. It is a monoclonal antibody that recognises and attaches itself to disialoganglioside - present in high amounts on the surface of neuroblastoma cells, but in lower amounts in normal cells – marking them out for destruction by the immune system.
For further information

 
The EMA approves Repatha to lower cholesterol in patients with homozygous familial hypercholesterolaemia
 
The European Medicines Agency (EMA) has recommended the authorisation of Repatha (evolocumab) to lower high levels of cholesterol in the blood of people who are unable to control their cholesterol despite taking optimal doses of statins or who cannot take statins. It is also indicated to treat people with homozygous familial hypercholesterolaemia, a rare inherited disorder in which levels of LDL cholesterol are higher than normal from birth. In addition to a healthy diet EMA recommends that other lipid lowering therapies (statins and others) should also be used, if tolerated, with Repatha. Repatha blocks the production of a protein PCSK9 protein, which would otherwise lower the number of LDL receptors in the liver and through this, thus diminishing its ability to remove LDL cholesterol from the blood.
For further information

 
EMA recommends Imbruvica for the treatment of Waldenstrӧm’s macroglobulinaemia
 
The European Medicines Agency (EMA) has recommended marketing authorisation for Imbruvica (ibrutinib) to treat patients with Waldenstrӧm’s macroglobulinaemia, a rare blood cell cancer. Waldenstrӧm’s macroglobulinaemia, a type of non Hodgkin lymphoma, is characterised by an excess of abnormal white blood cells, called B lymphocytes and plasma cells, in the bone marrow and sometimes in other organs. Imbruvica, the first medicine recommended for this disease, works by blocking an enzyme called Bruton’s tyrosine kinase, which aids in the survival of B lymphocytes and their migration to the organs where these cells normally divide, thereby delaying the progression of the cancer.
For further information

 


 
FDA approves Rapamune for the treatment of LAM a rare, progressive lung disease
 
The U.S. Food and Drug Administration (FDA) approved Rapamune (sirolimus), the first drug to treat lymphangioleiomyomatosis (LAM), a rare, progressive lung disease that primarily affects women of childbearing age. LAM is a very rare disease characterised by an abnormal growth of smooth muscle cells that invade lung tissues, including the airways, and blood/lymph vessels that cause destruction of the lung, resulting in airflow obstruction, and limiting the delivery of oxygen to the body. Rapamune, was originally approved in 1999 as an immunosuppressive agent to help prevent organ rejection in patients receiving kidney transplants. Recently it received breakthrough therapy designation and a priority review, due to the demonstration of its promise in other conditions.
For further information

 
Positive opinions recommending orphan designation at the April and May 2015 COMP meeting
 
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted thirteen positive opinions issued at the April 2015 COMP meeting for:

- treatment of ovarian cancer
- 2 treatments of Huntington’s disease
- treatment of mucopolysaccharidosis IIIC (Sanfilippo C syndrome)
- treatment of myasthenia gravis
- treatment of plasma cell myeloma
- treatment of non-infectious uveitis
- treatment of cystic fibrosis
- treatment of thromboangiitis obliterans (Buerger's disease)
- treatment of perinatal asphyxia
- treatment of diffuse large B-cell lymphoma
- treatment of oculopharyngeal muscular dystrophy
- treatment of glucose transporter type-1 deficiency syndrome

The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted thirteen positive opinions issued at the May 2015 COMP meeting for:

- treatment of non-infectious uveitis
- prevention of bronchopulmonary dysplasia
- prevention of scarring post glaucoma filtration surgery
- treatment of marginal zone lymphoma
- treatment of follicular lymphoma
- treatment of hepatitis delta virus infection
- treatment of haemophilia B
- treatment of spinal muscular atrophy
- treatment of amyotrophic lateral sclerosis
- treatment of spinocerebellar ataxia
- treatment of very long-chain acyl-CoA dehydrogenase deficiency

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

 
Political and Scientific News
 
Exploring the qualifying criteria for Breakthrough therapy designation by FDA
 
Breakthrough Therapy Designation (BTD), established by the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012, is one of several programs available to the U.S. Food and Drug Administration (FDA) to expedite the development and review of drugs and biologics for serious diseases and conditions. In order to qualify for a breakthrough therapy designation, "a candidate therapy must be intended to treat a serious or life-threatening illness, and preliminary clinical evidence must indicate that the therapy may demonstrate a substantial improvement over existing therapies on at least one clinically significant endpoint."

On April 24, under a cooperative agreement with FDA, the Center for Health Policy convened a public meeting to discuss the qualifying criteria for this special designation. To aid the workshop Brookings Institute published a discussion paper and a slidedeck with examples of drugs that were granted Breakthrough Designation. Using actual and hypothetical cases, the paper provides a detailed analysis of the qualifying criteria for BTD, as well as clarify the Agency’s application of the qualifying criteria to varying clinical development programs.
Access the paper and slidedeck

 
Regulatory approval and reimbursement for oncology drugs lacking Phase III data in Australia
 
A study published in Value in Health Regional Issues compares under what circumstances oncologics can obtain both regulatory and reimbursement approval in Australia when Phase III trial data are not favourable but the condition has no other therapeutic option and early-stage data are compelling. The authors extracted data from the "Therapeutic Goods Administration (TGA) Australian Public Assessment Reports, the European Medicines Agency, Food and Drug Administration, and Pharmaceutical Benefits Advisory Committee (PBAC) Public Summary Documents for any oncologic indication appraised in Australia on a pivotal trial package lacking phase III data, excluding paediatric indications and new formulations."

The results of the study, the authors concluded that “oncologic submissions that lack supportive phase III comparative data can attain TGA regulatory approval in Australia if they meet the following requirements 1. Evidence for efficacy is convincing and either the 2. Condition is rare or 3. The condition is a life-threatening one for which no other therapy is available.

The article also reported that public reimbursement through PBAC was possible if the medication can "demonstrate satisfactory cost-effectiveness using acceptable cost-benefit metrics and it contains more rigorous, substantial clinical data indicating dramatic benefits over the relevant comparators than was necessary for regulatory approval.”
Read the Open Access article

 


 
Grants
 

 
AFM Telethon: Call for proposals
 
Several call for proposals are being made available by AFM Telethon. They have published a call for proposals for Spinal Muscular Atrophy and Collagen VI Call for Projects.
For further information

 
Care-for-rare science award 2015
 
The Care-for-Rare Foundation awards two prizes a year, in order to encourage young researchers to continue their research into rare diseases. The Dr. Holger Müller Prize, endowed with €5000, is awarded to individual researchers or research groups who have published an outstanding contribution to the study of rare diseases in the previous year.
For further information

 
Neuronal Ceroid Lipofuscinosis Research Award
 
For the sixth time the Foundation announces and donates the NCL Research Award. They invite medical and basic science researchers worldwide to submit innovative project proposals that are either clinically oriented or cover translational aspects of CLN3 biology which can contribute to finding a cure for juvenile NCL. We particularly encourage also submissions from scientists working in related biomedical areas such as other lysosomal storage diseases, endolysosomal cell biology and neurodegenerative disorders. Together with the existing NCL research community our goal is to move promising therapeutic avenues forward to help JNCL patients. The grant (50,000 euros) serves as seed money supporting a one year postdoctoral fellowship to help young scientists progressing CLN3 research in academia or industry. Deadline: October 31, 2015
For further information

 
Call 4 Proposals (2015): Research Osteogenesis Imperfecta (OI)
 
The aim of this call is to (co) fund projects that will generate better treatment of Osteogenesis Imperfecta. Researchers responding to this call can come from any country. A wide range of treatment or research strategies will be considered. No area will be excluded as long as the quality of life of people with OI can be improved in a tangible and sustainable manner. All disciplines that contribute to the wellbeing of people with OI are invited to join. Creation of alliances and partnerships across national boundaries and medical institutions are explicitly welcomed, especially if they inclue collaboration with a partner form The Netherlands. Application deadline: 15 July 2015.
For further information

 
The Histiocytosis Association Call for proposals
 
The Histiocytosis Association is pleased to announce that our 2015 Research Program is now accepting proposals focusing on the causes, mechanisms, and improved means of treatment for histiocytic disorders. Proposals must be received online by July 1, 2015. Grant awards will be up to $50,000 USD each.
For further information

 
Fondation Jerome Lejeune grant application
 
Scientific Advisory Board of the Jérôme Lejeune Foundation invites submission from research projects aiming at deciphering the pathophysiology of the cognitive deficits of patients, especially those with trisomy 21 (Down syndrome) and other rare abnormalities such as fragile X, cri du chat, Rett, Williams-Beuren, Prader-Willi, Angelman, and other syndromes, excluding autism. - See more http://www.fondationlejeune.org/en/our-missions-and-actions/research/apply-for-a-grant-obtain-funding#sthash.vKIIZgmo.dpuf
 


 
Partnersearch, Job Opportunities
 
PhD fellowships from Kindness for Kids foundation
 
In collaboration with EuroBioBank and RD-Connect this PhD fund a PhD project that uses an in vitro experiment to help develop a new treatment in the area of rare paediatric diseases. For the project to be eligible, patient biomaterials from EuroBioBank and/or RD-Connect should be used in the study. The PhD project should develop or test a new treatment, identify therapeutic targets or employ a screening platform in the area of rare paediatric diseases using in vitro experiments. The experimentations of the PhD project must be to a major extent based on samples from a biobank associated with EuroBioBank and/or RD-Connect. Further collaborations with these two initiatives are strongly encouraged. The application has to be emailed in English as pdf attachments by June 15th 2015 to Dr. Julia Barske.
 
ECRIN ERIC job vacancies
 
ECRIN‐Eric is currently in the process of recruiting for its office based in Paris (France) a Capacity Project Manager, an Operations Project Manager and a Secretary. This is a unique opportunity for a motivated individual who wishes to further develop his/her career in biomedical research and his/her experience of multinational research projects. The ECRIN Capacity Project Manager will be in charge of the project management for the structuring projects with ECRIN involvement.
For further information

 


 
Courses & Educational Initiatives
 

 
2015 Genodermatoses Network Training Session
 
Date: 19 June 2015
Venue: Lasi, Romania

This training session is aimed at Health care providers including physicians -such as dermatologists, pediatricians, neonatologists- researchers, students, residents and others who can work together in the field of genodermatology. Topics will include discussions around ectodermal dysplasia, epidermolyisis bullosa, ichtyosis, neurofibromatosis, netherthon syndrome, nevus comedonicus, porphyria, tuberous sclerosis.
Visit the Genodermatoses website for more information.

 
Genetics of intellectual disability: an update
 
Date: 25 – 27 June 2015
Venue: Braga, Portugal

The aim of this course is to provide an update on the genetic basis of intellectual disability (ID). ID is a prominent feature in a large and heterogeneous set of hereditary conditions. This course is planned for a target audience of Pediatricians, Pediatric Neurologists, Pediatric Psychiatrists, Medical Geneticists, Psychologists, Family doctors, and graduate students in the fields of Neurosciences and Genetics. Other health professionals are also welcome. The course idiom will be English.
For more information.

 
3rd radiz Rare Diseases Summer School
 
Date: 1-3 July, 2015
Venue: Zurich, Switzerland

The 3rd radiz Rare Diseases Summer School will focus on a wide variety of subjects in the arena of rare diseases, from disease mechanisms and animal models, to improving diagnoses, to novel therapeutics. There will be lectures and workshops on drug development, model organisms, how to choose clinical endpoints, clinical trials, regulatory aspects, patient registries, patient initiated research, ethical considerations, as well as what rare diseases may tell us about common diseases. The summer school will contain lectures by national and international rare disease experts, workshops, and poster presentations by participants.
For more information.

 
Workshop on haemophilia registries
 
Date: 1 -2 July 2015
Venue: London, United Kingdom

The aim of this workshop will be to identify strengths and weaknesses of registries from the perspective of providing safety and efficacy data on products, and to consider approaches/initiatives to strengthen this.
For more information.

 
The 2nd Biennial Australian Rare Lung Disease Short Course
 
Date: 16-17 October, 2015
Venue: Sydney, Australia

The joint venture between Lung Foundation Australia and the Thoracic Society of Australia and New Zealand (TSANZ) will provide updates on the latest in research, diagnosis, therapy and care for Interstitial Lung Disease. The program boasts an exceptional selection of Australian specialists as well as keynote presentations from international speaker, Professor Kevin Flaherty (USA).
For further information or to register please visit: www.lungfoundation.com.au.

 
3rd International Summer School on Rare Disease and Orphan Drug Registries
 
Date: 21-23 September, 2015
Venue: Rome, Italy

The School will train participants on the methodologies and resources available for the establishment of a clinical research registry and on the implementation of successful strategies to ensure long time sustainability of the registry, including data sharing and dissemination activities.
For more information.

 
RD-Connect Workshop Data linkage and ontologies
 
Date: 24-25 September, 2015
Venue: Rome, Italy

The RD-Connect (http://rd-connect.eu) workshop will allow attendants to learn new concepts and tools for applying ontologies to their data and make them interoperable with other data coming from different sources.
For more information.

 
Courses offered by Recordati Rare Diseases Foundation
 
The Recordati Rare Diseases Foundation is offering five courses planned for next year. For further information, please contact Cecilia Kellquist, Coordinator and member of the board, ckellquist@rrd-foundation.org/www.rrd-foundation.org.
Classification and diagnostic approach of IMD affecting the synthesis and remodelling of complex lipids
Date: 24-26 June 2015
Venue: Paris, France

in partnership with the Pitié-Salpêtrière Hospital Pierre et Marie Curie University Paris VI; the Academic Medical Center, University of Amsterdam and the University Children’s Hospital of Zurich.
Registration deadline: 13th May

Genetic congenital heart diseases
Date: 7-9 October 2015
Venue: Rome, Italy

in partnership with Bambino Gesù Children’s Hospital, Rome
Registration deadline: 27th August

Neurotransmitter focus course
Date: 9-10 November 2015
Venue: Venice, Italy

in partnership with University Hospital for Child and Adolescent Medicine of Heidelberg and University Hospital of Padua. Registration deadline: 26th September

 
European Cytogenetesists Association
 
Date: February/March of each year
Venue: Nimes, France

This course 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-organized by E.C.A. 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. An application for CME points will also be made for 2016.
For more information.

 


 
What's on Where?
 

 
The European Human Genetics Conference 2015
 
Date: 6-9 June, 2015
Venue: Scotland, United Kingdom

The European Human Genetics Conference is a forum for all workers in human and medical genetics to review advances and develop research collaborations.
For further information

 
34th Annual European Malignant Hyperthermia Group (EMHG) Meeting
 
Date: 11-13 June, 2015
Venue: Lille, France

The topics will cover all the fields of interest in malignant hyperthermia, such as invitrocontracturetesting, genetics, clinical and experimental issues, updates and forthcoming projects. The scientific program of the European Malignant Hyperthermia Group (EMHG) will be on state-of-the-art presentations in our field as well as new insights into basic science, clinical research and therapeutic interventions.
For further information

 
22nd International Meeting of the Pediatric Colorectal Club 2015
 
Date: 13-15 June, 2015
Venue: Milan, Italy

This meeting aims to provide up to date clinical and scientific information on all aspects of paediatric colorectal disease to practicing paediatric surgeons, nurses and parents’ Associations.
For further information

 
International Myotonic Dystrophy Consortium Meeting (IDMC)
 
Date: 8-12 June, 2015
Venue: Paris, France

This consortium will bring together not only scientists and clinicians but also family associations and patients.
For further information

 
3rd ELA Scientific Congress
 
Date: 24-26 June, 2015
Venue: Paris, France

Speakers with expertise in leukodystrophies, myelin biology, neuroimaging, stem cell research and gene therapy will participate to the congress to share and discuss recent advances and cutting-edge science in these fields with the ultimate goal to fight and eventually find a cure for the disabling leukodystrophies and myelin diseases.
For further information

 
Tourette Syndrome Congress 2015
 
Date: 24-26 June, 2015
Venue: London, UK

The 1st World Congress on Tourette Syndrome and Tic Disorders is designed for linicians, researchers , post-doctoral fellows, medical residents and allied healthcare professionslas with an interest in current research, diagnosis and treatment of these and related conditions.
For further information

 
7th International Conference on Children’s Bone Health
 
Date: 27-30 June, 2015
Venue: Salzburg, Austria

The International Conference on Children’s Bone Health (ICCBH) meetings provide an international forum for the presentation and discussion of current basic and clinical science in the field of bone metabolism and bone mass in children, adolescents and young adults.
The call for abstracts opens in September 2014.
Abstract deadline: 6 February 2015.
For further information

 
Orphan Drugs & Rare Diseases Global Congress
 
Date: 29 June- 1 July, 2015
Venue: London, United Kingdom

This conference provides a unique platform for an intimate & interactive knowledge sharing and convergence of top tier government, pharmaceuticals, biopharmaceuticals, hospitals, non-profit organisations, orphan drugs developers as well as regional and local manufacturers to discuss the driving macroeconomic factors, policies and issues that will steer the development of orphan drugs globally.
For further information

 
The First Russian Congenital Aniridia Conference
 
Date: 3-4 July, 2015
Venue: Moscow, Russia

The conference will aim at sharing knowledge and experience about Congenital Aniridia by increasing the dialogue between patients and doctors about the problems of congenital aniridia.
For further information

 
10th European Cytogenetics Conference
 
Date: 4-7 July, 2015
Venue: Strasbourg, France

The 10th European Cytogenetics Conference allows all cytogeneticists from Europe and further afield to come together to hear about and discuss the most exciting developments ranging from applications in prenatal or cancer diagnosis to chromosome biology in epigenetics and evolution.
For further information

 
4th Congress on Mitochondrial Medicine
 
Date: 9-10 July, 2015
Venue: Salzburg, Austria

The meeting addresses the importance of mitochondrial pathology in neurology, pediatrics and beyond. An overview on the newest research developments and important clinical aspects will be provided. Deadline for the submission of scientific abstracts is May 15th and for early registration is June 1st.
For further information

 
10th International Conference: One Carbon Metabolism, vitamins B and Homocysteine
 
Date: 7-11 July, 2015
Venue: Nancy, France

The conference will deal with a very interdisciplinary program joining leading scientists from biochemical, experimental and clinical medical area. It will cover the most advanced research on One Carbon Metabolism, Homocysteine and related coenzymes and vitamins, including folate, vitamin B12 (cobalamins), vitamin B6 (pyridoxine) and choline in the fields of biochemistry, metabolism, nutrition, epidemiology and experimental and clinical medicine.
For further information

 
Genetic Alliance UK Annual Conference 2015
 
Date: 14 July, 2015
Venue: London, United Kingdom

The day will be a celebration of what they, as an alliance of member organisations, have collectively achieved over the past 25 years to make a difference to all those affected by genetic conditions.
For further information

 
4th International RASopathies Symposium
 
Date: 17-19 July, 2015
Venue: Washington, US

This conference will bring together caregivers, clinicians, patients, researchers and pharmas with an aim to expedite treatments and cures for the RASopathies.
For further information

 
Glycoproteinoses: Fourth International Conference on Advances in Pathogenesis and Therapy
 
Date: 23-26 July, 2015
Venue: Missouri, US

The Fourth International Conference on the Glycoproteinoses will bring together leading investigators from around the world to discuss the latest advances in understanding the pathophysiology of these rare disorders and the status of the development of new therapies.
For further information

 
International VHL Symposium for young adults
 
Date: 30 July – 3 August, 2015
Venue: Utrecht, The Netherlands

The aim of the event is to create the opportunity to network and share global experiences with VHL. Another important part of the programme is designed to increase age-specific VHL-related knowledge.
For further information

 
SSIEM Official Satellite Symposia Second World Conference on Congenital Disorders of Glycosylation
 
Date: 28-30 July, 2015
Venue: Lyon, France

This conference aims to raise awareness about Congenital Disorders of Glycosylation (CDG) around the world and to foster an exceptional collaborative model involving patients, family members, researchers and physicians.
For further information

 
SSIEM Annual symposium
 
Date: 1-4 September, 2015
Venue: Lyon, France

For further information

 
26th European Dysmorphology Meeting
 
Date: 9-10 September, 2015
Venue: Le Bischenberg, France

The principal aim of this meeting has been to bring young clinical geneticists and trained dysmorphologists together to share their professional experiences and present their clinical challenges. EuroDysmorpho is open to any presentation in the field of human development.
For further information

 
DEBRA International Conference & EBCLINET
 
Date: 24-26 September, 2015
Venue: London, United Kingdom

The 3rd conference of EB-CLINET is open to all network partners as well as other interested people who would like to gain a better understanding of the condition, the network and/or contribute to improving the medical care or the quality of life for those affected by EB.
For further information

 
Tyrosinemia 2015
 
Date: 24-26 September, 2015
Venue: Quebec, Canada

The Quebec parent association (GAETQ) is organizing an international conference on Tyrosinemia. The objective is to share and update our knowledge regarding this disease and its impacts on the medical world. Tyrosinemia was identified fifty years ago and used to greatly diminish the life expectancy of children affected. Now the disease is well controlled, thanks to NTBC.
For further information

 
The PANDAS 2015
 
Date: 26 September, 2015
Venue: Lake Como, Italy

Presentations of the latest scientific advances in the diagnosis and treament of PANS/PANDAS shall include topics touching immunology, rheumatology, neurology, child psychiatry, psychology and more.
For further information

 
8th International Congress of Familial Mediterranean Fever and Systemic Autoinflammatory Diseases
 
Date: 30 September – 3 October, 2015
Venue: Dresden, Germany

This meeting will offer numerous opportunities to convene with experts on FMF and other auto-inflammatory diseases. This meeting hopes to welcome more than 400 participants from all over the world to discuss the latest scientific and clinical developments, including new treatment options.
For further information

 
Annual joint DIA/EFGCP/EMA Better Medicines for Children Conference
 
Date: 1-2 October, 2015
Venue: London, UK

This year’s DIA/EFGCP/EMA annual paediatric conference will focus on ways to overcome challenges faced during drug development for the paediatric population, such as through collaboration, extrapolation, modelling & simulation and adaptive pathways.
For further information

 
2nd conference on European Reference Networks
 
Date: 8 – 9 October, 2015
Venue: Lisbon, Portugal

This conference will bring together highly specialised healthcare providers, experts, national authorities, decision–makers, and independent bodies with experience in the assessment and evaluation of healthcare providers.
For further information

 
47th Congress of the International Society of Paediatric Oncology
 
Date: 8 – 11 October, 2015
Venue: Cape Town, South Africa

This stimulating scientific programme will facilitate the exchange of ideas and information in paediatric oncology.
For further information

 
Xth Annual ICORD Meeting, part of the Global Rare Diseases Week, Mexico
 
Date: 15-16 October (ICORD), 12-16 October (Global Rare Disease Week, Mexico)
Venue: Mexico City, Mexico

ICORD 2015 will be held in México FD (México) 15-16 October in association with FEMEXER (the Mexican Federation of Rare Diseases) and GEISER Foundation (the Group of Linkage, Research and Support for Rare Diseases in Latin America). The event is part of the “Global Rare Diseases Week, Mexico 2015″ and back to back with the 4th Latin American meeting of Rare Diseases on October 12 and the Discoveries and Innovations in Orphan Drugs Congress, October 13-14.
For further information

 
The AANEM Annual Meeting
 
Date: 28 -31 October, 2015
Venue: Hawaii, United States

The AANEM Annual Meeting is the premier educational event for those involved in neuromuscular (NM) and electrodiagnostic (EDX) medicine. Earn over 30 continuing education credits through interactive workshops, lively discussions, and engaging sessions.
For further information

 
First European Congress on Hereditary ATTR amyloidosis ECATTR
 
Date: 2-3 November, 2015
Venue: Paris, France

The European Congress for HATTR will allow the meeting of the specialists of all European countries and the sharing of experience. The effort will be to further improve the early diagnosis of sporadic cases and genetic carriers, to review anti-amyloid treatments and clinical trials, to improve genetic counselling.
For further information

 
2nd International Primary Immunodeficiencies Congress (IPIC)
 
Date: 5-6 November, 2015
Venue: Budapest, Hungary

The International Patient Organisation for Primary Immunodeficiencies (IPOPI) announces the Second International Primary Immunodeficiencies Congress (IPIC). This event will build on the successful outcomes of the first IPIC, attended by 400 participants. The congress will consist of a two-day programme and is open to all stakeholders with an interest in clinical management of primary immunodeficiencies (PIDs).
For further information

 
16th International Conference on Human Genome Variation and Complex Genome Analysis
 
Date: 11-13 November, 2015
Venue: California, United States

HGV2015 will bring together approximately 180 delegates (selected on the basis of their abstract submission) in a workshop-style atmosphere, with 25 internationally recognized speakers
For further information

 
International Conference on Sanfilippo Syndrome and related Lysosmal Storage Diseases
 
Date: 26 – 28 November, 2015
Venue: Geneva, Switzerland

The aim of this second unique forum is to bring together some 200 participants from around the world, including scientists and clinicians, start-up leaders, and families of patients groups, to inform and strengthen exchange and cooperation.
For further information

 
MYOLOGY 2016 Fifth International Congress of Myology
 
Date: 14-18 March, 2015
Venue: Lyon, France

Held for the first time in 2000, MYOLOGY has become a unique opportunity for international experts in the field to exchange and confront the emerging therapeutic approaches, but also to share the first clinical results. The science and medicine of muscle have reached a new milestone. In Myology 2016, no doubt there will be new results, new breakthroughs to share all together.
For further information

 
13th International Congress of Human Genetics (ICHG) 2016
 
Date: 3-7 April, 2016
Venue: Kyoto, Japan

Hosted by the East-Asian Union of Human Genetic Societies (EAUHGS) and the Japan Society of Human Genetics, the 13th ICHG will focus on progress in genome analysis technologies and big data in order to explore disease mechanisms and treatment opportunities.
Registrations open in 2015.
For further information

 
ESID European Society for Immunodeficiencies: Biennial meeting
 
Date: 21-24 September, 2016
Venue: Barcelona, Spain

Sessions at this meeting will be devoted to understanding primary immunodeficiencies and their clinical aspects.
For further information

 

Commercial events

 
Orphan Drugs Summit 2015
 
Date: 17-18 September, 2015
Venue: Copenhagen, Denmark

This conference will bring together different groups of stakeholders on specifically selected topics to help them build relationships and reach their goals.

 


 
OrphaNews, The Newsletter of the Rare Diseases Community.
OrphaNews is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Divya Unni
Editors for Scientific Content: Sophie Höhn
Contact Us
Editorial Board: Ségolène Aymé, Paul Boom, Anna Bucsics, Kate Bushby, Lorenzo Dagna, Adam Heathfield, Lilian Lau, Yann Le Cam, Jordi Llinares-Garcia, Antonia Mills, Antoni Monserrat, Ana Rath, Charlotte Rodwell, Gerhard Steffes, Till Voigtländer, Jaroslaw Waligora

INTERNATIONAL CORRESPONDENTS
Orphanet Partner Country Representatives: Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Joerg Schmidtke (Germany), Helen Michelakakis (Greece), Eileen Treacy (Ireland), Annick Raas-Rothschild (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Vaidutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
Orphanet - All rights reserved
Photo credit : Serimedis http://www.serimedis.inserm.fr/ (unless otherwise stated)