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A week of ERN-related events in Brussels

The week commencing 26th September saw a host of activity in Brussels, around the hot topic of European Reference Networks (ERNs), culminating in a major RD-ACTION workshop addressing key issues pertaining to virtual care provision. Earlier in the week, the Board of Members States of ERNs – the executive body overseeing the implementation and evaluation of the Networks- met to discuss key issues in this important stage of the road to ERNs (the 24 proposals submitted to the European Commission earlier this year are currently being assessed by Independent Assessment Bodies). This was followed by the final workshop of the PricewaterhouseCoopers Services Tender developing a catalogue of services and a costing model for ERNs, which identified many factors and complexities associated with costing such an innovative means of healthcare organisation.

The 28 and 29th of September were devoted to a meeting and workshop organised by the Joint Action for Rare Diseases, RD-ACTION, continuing to cement the role of rare disease Joint Actions over the last four years in helping to bring the ERN concept to fruition.

Meeting between the Board of Member States and the Applicant Network Coordinators
On the morning of Wednesday 28th, RD-ACTION invited a representative from each of the proposed ERNs to join members of the Board of MS in a ‘pre-workshop’ meeting. This was the first occasion for these two essential stakeholder groups to come together in this way and discuss their most pressing issues relating to the implementation and evolution of the Networks. The meeting was attended by 14 representatives from 12 Member States and 19 Applicant Networks Coordinators (ANCs). The meeting focused discussions around two main topics:

1. Geographical membership coverage of the ERNs and means of ‘affiliation’ to the Networks. The discussions clarified the rules for future membership of the Networks, and the participants agreed the importance of gaining greater clarity of the timelines and process by which MS will designate centres as ‘affiliated’ partners to participate in an ERN, thus ensuring that countries (especially the smaller countries) which do not have -and are perhaps unlikely to have in the future- a member in a given ERN nonetheless have a ‘hub’/‘gateway’ to access and contribute to the expertise of that particular ERN.
2. Integration of ERNs with national health systems. The participants emphasised the potential for ERNs to, in time, bring about major innovation in health systems, functioning as true game changers in terms of equity of access across Europe to high quality care for patients whose conditions require a particular concentration of expertise. The challenges and opportunities on the sides of the ANCs and the Board members were shared in lively debate.

RD-ACTION Workshop
After a successful first meeting between these key stakeholders, the venue became the stage for the RD-ACTION Workshop on ‘Sharing data for virtual care within the framework of ERNs’. This topic was selected because at the heart of the ERN concept is the opportunity to provide healthcare through virtual means, enabling expertise to travel as opposed to patients or physicians, where possible and appropriate. The workshop was very well attended, with over 55 participants across the two days: 21 Applicant Networks; 10 European Commission DG SANTE experts leading various aspects of the ERN work, including Mr Andrzej Rys and Enrique Terol; 10 European Patient Advocacy Groups (ePAGs); experts from RD-ACTION and several other projects with experience and expertise in the standardisation of data in the RD field; and a legal expert with many years of experience in addressing the legal challenges facing the field of eHealth, Petra Wilson.

The workshop focused on several aspects relating to the organisation and execution of ‘virtual consultations’ for complex patient presentations requiring access to the pooled expertise of the ERN:

- The form such encounters might take were explored (for example a real-time gathering of experts through virtual systems, the ability to review uploaded case information in the professional’s own time through a secure platform, etc.)
- The legal issues around data protection -especially in view of the new General Data Protection Regulation- and the legal, ethical and social issues relating to consent for the sharing of data in the ERN framework
- Practical advice on the organisation and execution of efficient and effective virtual consultations, from colleagues engaged in this work at present
- Perspectives on how patients will enter/ be ‘referred’ to the expertise of the ERN for virtual care
- Experiences and recommendations on the standardisation of data in the RD field, in terms of disease coding and ontologies for phenotypic (clinical) information, to explore the good practices which should be embedded in the ERNs and identify additional standards of importance to the ANCs.

The workshop ended with a switch in focus towards future RD-ACTION workshops geared towards the ERN community, with particular discussion on research opportunities (inspired by a stimulating presentation from Iiro Eerola of DG Research and Innovation) and rare disease registration. The presentations and report of the workshop will be accessible through the RD-ACTION website very soon, and work is now underway to generate specific, practical outputs relating to several of the topics above, to function as guidance for the Networks (by the Networks). The workshop achieved its policy-oriented goals, thanks to the active and enthusiastic contribution of all participants; in addition, however, the political value of these meetings was significant. Throughout the week, it was heartening to see the commitment to this cause from such key figures as Commissioner Vytenis Andriukaitis, Dr Andrzej Rys (Director of the Health systems and medical products and innovation Directorate at DG SANTE) and, as always, Enrique Terol (whose role in making the ERN concept a reality cannot be underestimated). There is a clear commitment to making this concept a success, from all stakeholder groups, and RD-ACTION will continue to deliver workshops and support the generation of guidance over the coming months.

National & International Policy Developments
Other International News
Report: United Nations Secretary-general’s High-level panel on Access to medicines
Last year, the United Nations Secretary-General Ban Ki-moon commissioned a High-Level Panel on Innovation and Access to Health Technologies. The panel "review(ed) and assess(ed) proposals and recommended solutions for remedying the policy incoherence between the justifiable rights of inventors, international human rights law, trade rules and public health in the context of health technologies." The report of their recommendations in published on the United Nations website.

Of interest to the rare disease community is the recommendation to initiate negotiations for a binding Research & Development Convention that delinks the costs of research and development from end prices to promote access to good health for all. This is to combat the rising prices of medications, which is commonly encountered by rare disease patients as orphan medicines can be expensive and unaffordable to many. Also of significance is their recommendation to governments requiring that the unidentified data on all completed and discontinued clinical trials be made publicly available in a format that is is internationally recognisable.

Cystic fibrosis foundation opens drug discovery lab with royalty from orphan drugs developed by them
A few years ago, the Cystic Fibrosis foundation hired a biotech company to develop more effective treatments which paid off in two new drugs and monetarily. Although a game changer for Cystic fibrosis patients, these drugs - Orkambi and Kalydeco - do not cure the disease and are extremely expensive. The royalties from these drugs were sold to Royalty Pharma by the foundation for USD 3.3 billion. This move invited some criticism as it seemed that the patient foundation had profited on the backs of the patients, who had to pay for the expensive drug (read in OrphaNews). But the foundation countered it by expressing its desire to route this money to further research. According to an article published in Science Magazine, the foundation is now funding a new drug discovery lab which will speed drug development, named the CFF Therapeutics Lab. This lab was developed to advance therapeutics for CF by engaging in original research as well as “generate and share tools, assays, and lead compounds, boosting its partners’ chances of finding treatments.”

According to the article “the lab devotes about 70% of its activity to original research with the remainder centered on developing resources for the rest of the scientific community.” The labs will also explore possible treatments utilising stem cells and gene-editing tools.
Access the article

Guidance Documents and Recommendations
Foetal alcohol syndrome: guidelines for diagnosis
Consult the Pubmed abstract
To read more about "Fetal alcohol syndrome"

Pediatrics ; 138(2) ; August 2016
Health risks for ataxia-telangiectasia mutated heterozygotes: recommendations
Consult the Pubmed abstract
To read more about "Ataxia-telangiectasia"

Clin Genet. ; 90(2):105-17 ; August 2016
Myasthenia gravis: recommendations for the management
Consult the Pubmed abstract
To read more about "Myasthenia gravis"

Neurology ; 87(4):419-25 ; July 2016
Bioinformatics, Registries and Data Management
Development and establishment of Kawasaki disease database in South Korea
An article published in Database describes the development of Kawasaki Disease Database in South Korea. This database contains clinical and genomic data of patients collected from hospitals participating in the Korean Kawasaki Disease Genetics Consortium. They also collected genome-wide association and whole exome sequencing data. According to the authors, this is the first public database which is able to significantly facilitate research on Kawasaki Disease.
Read the Open Access article

An example of the national sarcomas database in France
Sarcomas are rare and heterogeneous tumours that require sharing of data and biological materials to improve the care of patients. An article published in Cancer Bulletin details the creation and organisation of the French national database on sarcomas, which brings together about 60,000 patients in a data warehouse containing clinical, pathological, molecular, evolutionary and therapeutic as well as data on the available samples and medical practice.

The first national database on these tumours was established in 1989. In 2010, as part of the implementation by the National Cancer Institute (INCA) national networks for the management of rare cancers of the adult sarcoma three reference networks have been set up. But it was not until 2016 that the various databases have been compiled in a data warehouse (clinical and biological basis or sarcoma BCB), which currently includes the clinical and biological information about 60 000 patients. This pooling within structured national networks constitutes a major tool for the French Sarcoma Group to improve the knowledge and practice in this area and build an organisation of information in cancer model.
Access the article

Screening and Testing
The experience of the UK Huntington’s Prediction Consortium
According to an article in European Journal of Human Genetics, the UK Huntington’s Prediction Consortium has collected anonymised data on predictive tests offered in the United Kingdom, from participants who were on an average 37 years of age. According to the article, the primary motivation for testing for these participants was to reduce uncertainty, planning for the future and to decide on reproductive options. The authors calculated the cumulative uptake of testing and found that a large number of patients did not undergo predictive testing. The authors warn that "there are a number of active clinical trials; if even one of these identifies an agent that provides a neuroprotective effect in HD, then it is likely that the number of individuals requesting testing will increase and services will need to change."
Read the Pubmed abstract


Ethical, Legal & Social Issues
Ethical issues in the evaluation of adults with suspected genetic neuromuscular disorders
Results of genetic testing, which is rapidly becoming commonplace, can have potentially enormous consequences for the individual tested and for family members. In the context of adults undergoing testing for neuromuscular disorders, an article published in Ethics in Neuromuscular Genetics discusses the ethical considerations that physicians have to deliberate when performing genetic testing. The authors discuss the importance of informed consent as well as counseling as the key aspect of ongoing and subsequent interactions. The authors also draw emphasis on patient autonomy with regards to their right to know and not-to-know. According to the authors “the pace of discovery in the field of medical genetics necessitates continual self-education on the part of physicians who care for patients with neuromuscular disorders.”
Read the Pubmed abstract

The economics of producing treatments for rare cancers
In the Journal of Cancer Policy, the authors discuss the challenges and opportunities that affect the development of drugs for rare cancers. According to the authors, rare diseases present an extraordinary financial and organisational challenge for health care payers and describe the challenges in this regard. They also explore the predicaments encountered while setting prices for orphan drugs - balancing research and development costs of the drug with the ability of the patients to pay for it. The authors believe that "new concepts for defining the prices for drugs for rare diseases in general and rare cancers in particular have to be developed." They believe that "these criteria have to be transparent and the prices must be fair and fit with the overall remuneration schedules for health services and goods." They authors recommend that to "develop(ing) these pricing schemes, science has to develop better concepts to measure patient preferences and benefit."
Read the Pubmed abstract

The expectations of rare disease patients on large-scale data sharing for genomics research
An article published in European Journal of Human Genetics reports on the views of rare disease patients participating in genomics research. Here the authors document RD patients’ attitudes to participation in genomics research, particularly around large-scale, international data and biosample sharing. The authors "explore the views of people with a range of rare disorders from many different countries." The authors found that "expressions of trust and attitudes to risk are often affected by the nature of the rare disease as well as regulatory and cultural practices in their home country." Participants are concerned about data security and misuse. The authors also demonstrate that these patients recognise "the vulnerability inherent in having a rare disease and the possibility that open knowledge of this could lead to discrimination."
Read the Pubmed abstract

The myth of anonymity
An article in Nature explains the inherent difficulty of keeping health data of patients registered in genomic research anonymous. According to the article the Personal Genome Project as well as the Precision Medicine project promise to remove identifiable information of participants but do not promise complete anonymity. Several approaches have been discussed in the past to protect the identity, but many of these approaches results in depriving the researchers of data that may help them find a cure for their disease. Many Americans fear that courts may decide that when participants volunteer information to researchers, they give away their right to doctor–patient confidentiality and may lead to discrimination. According to the article, it is necessary to be clear on consent and there is an urgent requirement to “rethink how privacy and consent are handled, and to treat the people who hand over their DNA with respect and honesty.”
Read the article

The ethics of uncertainty in genomic medicine
In BMC Medical Genomics, the authors drafted a conceptual and ethical response to the question of how to conceive of and respond to uncertainty in genomic medicine. The authors suggest that genomic testing should not be offered merely as a means to reduce uncertainty; nor should uncertainty necessarily be framed negatively or as something that should always be eradicated. Instead, they recommend that the process of genomic testing should include an explicit consideration of uncertainty, both before and after testing. This should not involve mere education to reduce uncertainty, but encompass a richer engagement involving appraisal, adaptation and complex communication. They also suggest "several ethical concepts that can guide how uncertainty is handled: resilience, welfare, autonomy and solidarity." Overall, the authors state that the role of clinicians and counselors is to facilitate those receiving genomic information to come to terms with the certainties and uncertainties that arise during and after the testing process.
Read the Open Access article

EURORDIS survey on living with rare diseases
EURORDIS has recently launched a new survey on the impact of rare diseases on daily life, available in 23 languages.The survey is the first to be conducted via the Rare Barometer Voices survey panel.
Take part in the survey here Patients, parents and other family members can participate in this study. To ensure that results reflect the diversity of the rare disease community, it is crucial that as many people living with a rare disease as possible take part. The results will help EURORDIS and EURORDIS member organisations to advocate for better care and support for people living with a rare disease in Europe.

EURORDIS wants to hear how living with a rare disease has impacted the autonomy and daily life of people living with a rare disease and to learn more about the level of support they receive, how care is organised and the costs of care.

The results will be available for participants to use, per country (48 European countries), per disease when possible and in 23 languages. All participants will receive the results by email.

This survey is carried out in the scope of the INNOVCare project. This EU-funded project addresses the social challenges faced by people living with rare complex conditions and the gaps in the coordination between health, social and support services in European Union Member States.

For now, participants in Rare Barometer Voices must live in one of the 48 European continent countries. EURORDIS hopes to develop the programme to other continents in the future. Please contact Sandra Courbier, EURORDIS Surveys and Social studies Manager, with any questions: sandra.courbier@eurordis.org

Nominations for the EURORDIS Awards 2017 now open!

EURORDIS is now accepting nominations for the 6th Annual EURORDIS Awards! You can nominate the individual, rare disease patient organisation or company that you feel is making a difference to the rare disease community. It recognises and honours the exceptional contributions made by the patients, leaders, policy makers, scientists and companies who work relentlessly to reduce the impact that rare diseases have on millions of people.

Submit a nomination for any or all of the following categories:
European Rare Disease Leadership Award
Policy Maker Award
EURORDIS Volunteer Award
Scientific Award
Patient Organisation Award
Company Award
Media Award
Lifetime Achievement Award
Read the nomination criteria and fill out the nomination form (deadline 31 October 2016). The winners will be announced at the EURORDIS Awards Ceremony on 21 February 2017 in Brussels, held in celebration of Rare Disease Day 2017.
Previous EURORDIS Award Winners

Orphanet News
New Texts
Translation of Orphanet files dedicated to disability now in Spanish
First text focussed on Handicap translated into Spanish:
Marfan Syndrome

List of centres of reference for rare cancers in France
Now published in Orphanet
List of centres of reference for rare cancers in adults


New Syndromes

Possible novel autoimmune encephalitis
Five patients with a novel autoimmune encephalitis in which the antibodies target neurexin-3α, a cell adhesion molecule involved in the development and function of synapses, were described. Neurexin-3α autoantibodies associate with a severe but potentially treatable encephalitis in which the antibodies cause a decrease of neurexin-3α and alter synapse development.
Consult the Pubmed abstract

Neurology ; 86(24):2235-42 ; 2016 Jun 14

New Genes

Early-onset epileptic encephalopathy with cerebellar atrophy caused by gain-of-function FHF1 mutations
Consult the Pubmed abstract
To read more about "Undetermined early-onset epileptic encephalopathy"

Neurology ; 86(23):2162-70 ; June 2016
Arthrogryposis multiplex congenital associated with a novel homozygous mutation in MYBPC1 in a consanguineous family
Consult the Pubmed abstract
To read more about "Arthrogryposis multiplex congenita"

Clin Genet. ; 90(1):84-9 ; July 2016
Thoracic aortic aneurysm and dissection due to loss of function mutation in LOX
Consult the Pubmed abstract
To read more about "Familial thoracic aortic aneurysm and aortic dissection"

Proc Natl Acad Sci U S A. ; 113(31):8759-64 ; August 2016
Uveal melanoma linked to recurrent activating mutations in CYSLTR2
Consult the Pubmed abstract
To read more about "Uveal melanoma"

Nat Genet. ; 48(6):675-80 ; June 2016
B-cell acute lymphoblastic leukaemia of adolescents and young adults might be caused by recurrent DUX4 fusions
Consult the Pubmed abstract
To read more about "Precursor B-cell acute lymphoblastic leukemia"

Nat Genet. ; 48(5):569-74 ; May 2016
Pemphigus vulgaris: identification of a functional risk variant in the ST18 gene
Consult the Pubmed abstract
To read more about "Pemphigus vulgaris"

PLoS Genet. ; 12(5):e1006008 ; May 2016

Research in Action

Clinical Research
Down syndrome: vitamin E does not slow the progression of cognitive deterioration in older individuals
Consult the Pubmed abstract
To read more about "Down syndrome"

Neurology ; 86(22):2071-6 ; May 2016
POEMS syndrome: combination therapy with low-dose lenalidomide plus dexamethasone improves sexual function
Consult the Pubmed abstract
To read more about "POEMS syndrome"

Orphanet J Rare Dis. ; 11(1):80 ; June 2016
Myasthenia gravis: methotrexate does not show efficacy
Consult the Pubmed abstract
To read more about "Myasthenia gravis"

Neurology ; 87(1):57-64 ; July 2016
Systemic mastocytosis: midostaurin shows efficacy
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Systemic mastocytosis"

N Engl J Med. ; 374(26):2530-41 ; June 2016
Gitelman syndrome: slow-release magnesium lactate shows favourable outcomes
Consult the Pubmed abstract
To read more about "Gitelman syndrome"

Nephrol Dial Transplant. ; [Epub ahead of print] ; March 2016
Kawasaki disease: protective effects of breastfeeding
Consult the Pubmed abstract
To read more about "Kawasaki disease"

Pediatrics ; 137(6). ; June 2016
Therapeutic Approaches

Pronuclear transplantation can reduce the risk of mitochondrial disease, but it may not guarantee prevention
Consult the Pubmed abstract
Nature ; 534(7607):383-6 ; June 2016
Niemann-Pick disease type C: over-expression of HSPB1 in mice slows the progression of motor impairment and diminishes cerebellar Purkinje cell loss
Consult the Pubmed abstract
To read more about "Niemann-Pick disease type C"

PLoS Genet. ; 12(5):e1006042 ; May 2016
EEC syndrome: phenotypic correction of mutant stem cells by means of siRNA mediated allele-specific silencing with restoration of function
Consult the Pubmed abstract
To read more about "EEC syndrome"

Stem Cells ; 34(6):1588-600 ; June 2016
Tyrosinemia type 1: ex vivo gene therapy corrects the disease in a pig model
Consult the Pubmed abstract
To read more about "Tyrosinemia type 1"

Sci Transl Med. ; 8(349):349ra99 ; July 2016
Leber congenital amaurosis: treating optic cups with an antisense morpholino effectively blocks aberrant splicing and restores normal cilia-based protein trafficking
Consult the Pubmed abstract
To read more about "Leber congenital amaurosis"

Cell Stem Cell. ; 18(6):769-81 ; June 2016
Friedreich ataxia: herpes viral vector encoding for BDNF prevents the development of cerebellar neuropathology and the ataxic phenotype in culture and in mouse
Consult the Pubmed abstract
To read more about "Friedreich ataxia"

Mol Ther. ; 24(5):877-89 ; May 2016
Spinocerebellar ataxia type 6: adeno-associated virus-mediated delivery protects mice from the ataxia, motor deficits and Purkinje cell degeneration
Consult the Pubmed abstract
To read more about "Spinocerebellar ataxia type 6"

Sci Transl Med. ; 8(347):347ra94 ; July 2016
Amyotrophic lateral sclerosis: 4-aminopyridine restores ion-channel imbalance, increases neuronal activity level and decreases endoplasmic reticulum stress and caspase activation
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis"

Stem Cells ; 34(6):1563-75 ; June 2016
Kennedy disease: delivery of microRNA-298 results in efficient transduction of muscle and spinal cord and amelioration of the disease phenotype in mice
Consult the Pubmed abstract
To read more about "Kennedy disease"

Mol Ther. ; 24(5):937-45 ; May 2016
Zika virus disease: pregnancy and birth defects in experimental models
Consult the Pubmed abstracts
To read more about "Zika virus disease"

Nature ; 534(7606):267-71 ; May 2016
N Engl J Med. ; 375(5):481-4 ; August 2016
EUrd as a novel inhibitor against temozolomide-resistant glioblastoma-initiating cells
Consult the Pubmed abstract
To read more about "Glioblastoma"

Stem Cells ; 34(8):2016-25 ; August 2016
Severe combined immunodeficiency: generation of a marmoset model
Consult the Pubmed abstract
To read more about "Severe combined immunodeficiency"

Cell Stem Cell ; 19(1):127-38 ; July 2016
Diagnostic Approaches

Wilson disease: rapid and reliable diagnosis using X-ray fluorescence
Consult the Pubmed abstract
To read more about "Wilson disease"

J Pathol Clin Res. ; 2(3):175-86 ; June 2016
Differentiation of neurodegenerative parkinsonian syndromes by volumetric magnetic resonance imaging analysis and support vector machine classification
Consult the Pubmed abstract
Mov Disord. ; [Epub ahead of print] ; July 2016
Paediatric arterial ischemic stroke: adult stroke recognition tools perform poorly in children and require modification to be useful
Consult the Pubmed abstract
To read more about "Pediatric arterial ischemic stroke"

Neurology ; 86(23):2154-61 ; June 2016
Neurofibromatosis type I: quantitative MRI criteria for optic pathway enlargement
Consult the Pubmed abstract
To read more about "Neurofibromatosis type 1"
To read more about "Optic pathway glioma"

Neurology ; 86(24):2264-70 ; June 2016

Patient Management and Therapy
Fragile X syndrome: two reviews on clinical management and treatments
Consult the first abstract
Consult the second abstract

To read more about "Fragile X syndrome"

Intractable & Rare Diseases Research ; 5(3):145-157; 158-167 ; 2016
Review on retinal stimulation strategies to restore vision
Consult the Pubmed abstract
Prog Retin Eye Res. ; 53:21-47 ; July 2016
Rare central nervous system diseases: review on gene therapy
Consult the Pubmed abstract
To read more about "Metachromatic leukodystrophy"
To read more about "X-linked adrenoleukodystrophy"
To read more about "Juvenile neuronal ceroid lipofuscinosis"
To read more about "Sanfilippo syndrome type A"
To read more about "Sanfilippo syndrome type B"

Endocr Dev. ; 30:141-6 ; 2016
Duchenne muscular dystrophy: Cochrane review on corticosteroids for the treatment
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Cochrane Database Syst Rev. ; (5):CD003725 ; May 2016
Small cell lung cancer: review on chemotherapy
Consult the Pubmed abstract
To read more about "Small cell lung cancer"

Sci Transl Med ; 8(346):346fs12 ; July 2016
Low-risk gestational trophoblastic neoplasm: Cochrane review on chemotherapy
Consult the Pubmed abstract
To read more about "Gestational trophoblastic neoplasm"

Cochrane Database Syst Rev. ; (6):CD007102 ; June 2016
Bardet-Biedl syndrome: review on genetics
Consult the Pubmed abstract
To read more about "Bardet-Biedl syndrome"

Clin Genet. ; 90(1):3-15 ; July 2016
Rare mitochondrial disorders: review on diagnosis and treatment
Consult the abstract
Journal of Rare Disorders ; 4(1):44-58 ; 2016
Neonatal lupus: a review
Consult the Pubmed abstract
To read more about "Neonatal lupus erythematosus"

Curr Rheumatol Rep. ; 18(9):60 ; September 2016
Lupus, dermatomyositis and localised scleroderma: a review
Consult the Pubmed abstract
To read more about "Dermatomyositis"
To read more about "Localized scleroderma"

Dermatol Clin. ; 34(3):243-50 ; July 2016
Familial calcium pyrophosphate deposition: a review
Consult the Pubmed abstract
To read more about "Familial calcium pyrophosphate deposition"

N Engl J Med. ; 374(26):2575-84 ; June 2016
Haemophagocytic syndrome: review on diagnosis and therapies
Consult the Pubmed abstract
To read more about "Hemophagocytic syndrome"

Br J Haematol. ; 174(2):175-87 ; July 2016
Neuromyelitis optica: a review
Consult the Pubmed abstract
To read more about "Neuromyelitis optica"

Curr Rheumatol Rep. ; 18(8):54 ; August 2016
Pleuroparenchymal fibroelastosis of the lung: a review
Consult the Pubmed abstract
Arch Pathol Lab Med ; 140(8):849-53 ; August 2016
Clear cell sarcoma: a review
Consult the Pubmed abstract
To read more about "Melanoma of soft tissue"

Expert Rev Anticancer Ther. ; 16(8):839-45 ; August 2016
Squamous cell carcinoma of anal canal: a review
Consult the Pubmed abstract
To read more about "Squamous cell carcinoma of anal canal"

Nat Rev Clin Oncol. ; 13(7):447-59 ; July 2016
One new and seven 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. One new GeneReviews has been published for:
SCN8A-related epilepsy with encephalopathy
Seven updated GeneReviews have been published for:
Citrullinemia type I
Congenital dyserythropoietic anaemia type I
Glycogen storage disease type I
ATP7A-related copper transport disorders
Nonsyndromic hearing loss and deafness, DFNB1
Beckwith-Wiedemann syndrome
MED12-related disorders


Orphan Drugs
New treatment for patients with soft tissue sarcoma
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), reviewed Lartruvo under EMA’s accelerated assessment program and recommended conditional approval for the medicine. It has been recommended for the treatment of adults with soft tissue sarcoma, which can occur in muscles, blood vessels, fat tissue or tissues that support or surround it.

According to the EMA “it is recommended for use in combination with doxorubicin (a chemotherapy medicine) in patients with advanced soft tissue sarcoma for whom surgery or radiotherapy is not suitable, and who have not been previously treated with doxorubicin.”

However, the applicant must provide results from an ongoing Phase III study which “compares how long patients receiving doxorubicin plus Lartruvo survive compared with patients who only receive doxorubicin.”
Read the Pubmed abstract

Regulatory News
Positive opinions recommending orphan designations at the July and September COMP meetings

The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted eighteen positive opinions issued at the July 2016 COMP meeting for the:

- treatment of tracheal stenosis,
- 2 treatments of amyotrophic lateral sclerosis
- treatment of paroxysmal nocturnal haemoglobinuria
- treatment of ornithine translocase deficiency
- treatment of lysinuric protein intolerance
- treatment of McArdle’s disease
- 2 treatments of glioma
- treatment of idiopathic pulmonary fibrosis
- treatment of scedosporiosis
- treatment of mucopolysaccharidosis type I
- treatment of Duchenne muscular dystrophy
- treatment of retinitis pigmentosa
- treatment of graft-versus-host disease
- treatment of malignant mesothelioma
- treatment of cholangiocarcinoma
- treatment of pancreatic islet transplantation
- treatment of alkaptonuria
- treatment of systemic sclerosis
- treatment of glycogen storage disease type II
- treatment of acute radiation syndrome
- treatment of graft-versus-host disease
- treatment of acute hepatic porphyria

The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted fourteen positive opinions issued at the September 2016 COMP meeting for:

- treatment of invasive aspergillosis
- treatment of cystic fibrosis
- treatment of soft tissue sarcoma
- treatment of periventricular leukomalacia
- treatment of diffuse large B-cell lymphoma
- treatment of osteomyelitis
- treatment of haemophilia A
- treatment of gastro-entero-pancreatic neuroendocrine tumours
- treatment of cutaneous T-cell lymphoma
- treatment of myelofibrosis
- treatment of haematopoietic stem cell transplantation
- treatment of paroxysmal nocturnal haemoglobinuria
- treatment of multiple myeloma
- treatment of large B-cell lymphoma
- treatment of ischaemia reperfusion injury associated with cardiac arrest
- treatment of Smith-Magenis syndrome
- 2 treatments of retinitis pigmentosa
- treatment of neonatal encephalopathy
- treatment of metaphyseal chondrodysplasia
- treatment of mucopolysaccharidosis type IIIA (Sanfilippo A syndrome)
- treatment of soft tissue sarcoma
- treatment of acute myeloid leukaemia
- treatment of noninsulinoma pancreatogenous hypoglycaemia syndrome
- treatment of peripheral T-cell lymphoma
- treatment of leukocyte adhesion deficiency type I,

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
Orphan drug coverage decision in Australia, the Netherlands, Sweden, and the UK
Authors of an article published in Health Policy conducted an analysis of the different aspects that impacted decision making in drug coverage in 4 countries – Australia, the Netherlands, Sweden and the UK. In this comparative analysis the authors examined interagency agreement and process-related factors such as delay between Health Technology Assessment (HTA) evaluations, therapeutic indication and orphan drug status, measure of health economic value, and comparator to evaluate coverage decisions.

The results showed that agreement on coverage of the drug was poor to moderate across HTA agency listing recommendations in these 4 countries. However they also report that agreement increased as the delay between HTA agency appraisals decreased and when orphan drugs were assessed. According to the authors "international differences in drug listing recommendations seem to occur in part due to inconsistencies in how the supporting evidence informs assessment, but also to differences in how domestic priorities shape the value-based decision-making process."
Read the Pubmed abstract



Medical Research Grant Application Guidelines : Progeria Research Foundation
The foundation is proving several grants such as Innovator Awards, Established Innovator Award, and Specialty Award. Details are provided on their website
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

FDA providing USD 2 million in new grants for natural history studies in rare diseases
The aim is to collect data on how specific rare diseases progress in individuals over time so that knowledge can inform and support product development and approval. This will be the first time the FDA will provide funding through its Orphan Products Grants to conduct these types of studies for rare diseases. Deadline: 14 October, 2016
For further information

Myotubular trust - seventh call for projects (open to international applications)
The Myotubular Trust are holding a seventh call for research projects. They are 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.

We 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.
The deadline for receipt of applications is the Wednesday 30th November 2016
For further information

9th Call for SMA Research Proposals
This new Call for SMA Projects will be open to any research project (those of a collaborative nature are encouraged) aimed at finding a therapy for Spinal Muscular Atrophy (SMA) or at elucidating the basic pathophysiological processes of the disease. Priority will, however, be given to projects concentrating on the following areas:

a. Understanding and Function of the SMN Complex and possibly other factors, independent of SMN, as it relates to the pathophysiology of SMA
b. Innovative Approaches for Therapy of SMA, including targeting non-SMN pathways
c. Projects addressing bottlenecks impairing rapid translation from basic research to clinical trials, including;
•Innovative outcome measures & endpoints
•Appropriate methodology to follow disease progression and treatment effect.
The deadline for receipt of applications is the 8 December 2016.
For more information

NCL Research Award
The award is intended to support postdoctoral level fellowships. The foundation encourages junior scientists and clinical researchers worldwide to submit projects that hold promise to help halt or finding a cure for CLN3 disease. They also encourage scientists to apply that work in disease areas outside NCL but relevant to cell and molecular pathways of CLN3 dysfunction. The deadline for receipt of applications is the 31 October 2016.
For more information

Research Grants Available for Rare Diseases
Recently the National Organization for Rare Disorders (NORD) announced the availability of new research grants to study rare diseases. All U.S. and international researchers interested in studying these diseases are encouraged to apply. Any support you can lend to help spread the word would be greatly appreciated (press release attached). The deadline to submit abstracts is Oct. 21.

NORD's 2016 research grant funding is available for the study of: Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins – One (1) grant of up to $50,000, for scientific and/or clinical research studies related to Alveolar Capillary Dysplasia (ACD/MPV). Appendix Cancer and Pseudomyxoma Peritonei – Two (2) grants of up to $50,000 for scientific and/or clinical research studies related to Appendix Cancer and/or Pseudomyxoma Peritonei (PMP).

Autoimmune Polyglandular Syndrome Type 1 – One (1) grant of up to $100,000 for scientific and/or clinical research studies related to Autoimmune Polyglandular Syndrome Type 1 (APS Type 1).

Homocystinuria – One (1) grant of up to $30,000 for scientific and/or clinical research studies related to Homocystinuria due to Cystathionine Beta-Synthase Deficiency.

Malonic Aciduria – One (1) grant of up to $30,000 for scientific and/or clinical research studies related to Malonic Aciduria.

Stiff Person Syndrome – One (1) grant of up to $30,000 for scientific and/or clinical research studies related to Stiff Person Syndrome.

The NORD Research Grant Program provides seed-money grants to academic scientists for scientific and/or clinical research. The hope is that these studies will ultimately lead to new diagnostics, treatments, and/or cures for rare diseases. NORD's program provides grants for the study of diseases for which there are few other sources of funding. Grants provided through the NORD program are made possible by donations from individuals and organizations to restricted research funds at NORD.
For more information


Courses & Educational Initiatives

Introducing diagnostic applications of ‘3Gb-testing’ in human genetics
Date: 24-27 October, 2016
Venue: Lisbon, Portugal The focus of the course is on clinical diagnostics using exome/genome sequences, variant identification and analysis including afternoon practical sessions.
For more information

Metabolic Myopathies Course
Date: 3-5 November, 2016
Venue: Paris, France

Target audience and participant profile: Neurologists, neuromuscular specialists, internists, cardiologists, geneticists, pediatricians, biochemists, willing to improve their knowledge in the diagnosis and treatment of metabolic myopathies + differential diagnosis with other inherited or genetic myopathies. For further information, please contact Cecilia Kellquist, Coordinator and member of the board, ckellquist@rrd-foundation.org or visit www.rrd-foundation.org.

Orphan Drug and Rare Disease Seminar
Date: 18 November, 2016

Venue: Marseille, France

This Eudipharm training seminar aims at raising awareness among clinical research actors on drug development specificities for rare diseases. This edition will offer a first day on regulatory issues and the second day will focus on drug re-positioning and personalised medicine, thanks to the participation of clinical research experts and authorities.
For further information

European Advanced Postgraduate Course in Classical and Molecular Cytogenetics
Date: March, 2017

Venue: Nimes, France

For further information

An Online Educational Resource for Limb Girdle Muscle Weakness
Limb girdle muscle weakness (LGMW) can result from multiple causes. Early and accurate diagnosis is critical to optimal disease management. The diagnosis can involve clinical, electromyogram, and genetic findings. Patient specific multidisciplinary management plans, including genetic counseling, should be developed. Currently, there are drugs available for some conditions. Many providers lack the skills to provide optimal care due to the heterogeneous presentation, complex diagnosis, and rarity of LGMW disorders.
For further information

The 2016 Course on Ichthyosis
Date: 31 October, 4 November 2016
Venue: Iasi, Cluj, Romania

Both workshops will be organized with funding received from 2 projects: European Union's Horizon 2020 research and innovation programme under grant agreement No 667387 and PN-III-P1-1.1-MCD-2016-0033 Romanian project, with the help of my colleagues and Mariana Pinteala from "P.Poni" Research Institute.
For more information


What's on Where?

Melorheostosis Association Conference 2016
Date: 14 October, 2016
Venue: Rochestor, United States of America

For further information

The Annual Meeting of the Histiocyte Society
Date: 17-19 October 2016
Venue: Dublin, Ireland

The meeting will feature presentations by several experienced researchers regarding a variety of perspectives on the study and treatment of the histiocytic disorders.
For further information

RDCRN Conference on Clinical Research for Rare Diseases 2016
Date: 19 October, 2016
Venue: Washington D.C., United States of America

Attendees have the opportunity to:
• Meet key leaders in rare diseases research.
• Engage in formal and informal networking and idea generation with other trainees and investigators. • Discuss career development and strategic planning for academic success.
• Explore research collaborations.
For further information

Orphan Drugs and Rare Diseases
Date: 19-20 October 2016
Venue: London, United Kingdom

SMi’s 5th annual Orphan Drugs event will bring together leading industry professionals to discuss the latest regulatory developments, explore how to reduce costs and learn from the latest innovations in the orphan drug landscape.
For further information

RareX featuring ICORD 2016
Date: 19-22 October 2016
Venue: Cape Town, South Africa

ICORD, Rare Disease International and the Rare Disease Society of South Africa invite you to ICORD 2016 in Cape Town, South Africa. Taking place in the context of Rare Diseases Week 2016, this is the first time that ICORD will be held in Africa. Join us and contribute to a legacy of prevention, treatment and study of rare diseases in Africa and around the world.
For further information

International Symposium: Rare skin diseases: from clinic to gene and vice versa
Date: 20-21 October 2016
Venue: Madrid, Spain

The symposium is divided into 5 sections and a plenary lecture covering both the state of art in the clinical management of this set of diseases as well as current research and future prospects.
For further information

Conference on crossborder healthcare Directive ‘Towards amplified awareness of EU rights to crossborder care’
Date: 24 October 2016
Venue: Brussels, Belgium

This conference builds on the discussions that took place at the Informal Meeting of Ministers of Health held in Luxembourg in September 2015, as well as on the findings of the 2015 Commission report on the operation of the crossborder healthcare Directive and the Eurobarometer on Patient Rights published in May 2015.
For further information

Cambridge Rare Disease Network (CRDN) 2nd annual International Rare Disease summit
Date: 25 October 2016
Venue: Cambridge, England

This event is aimed at key stakeholders from the International rare disease community, also hosting in parallel a "Round Table of Companies" meeting to initiate a rare disease joint funding strategy. Contact CRDN Events Director jo@camraredisease.org

27th International Conference on Spina Bifida and Hydrocephalus
Date: 28-30 October 2016
Venue: Ghent, Belgium

The ‘Turning Points’ conference will look back on developments in three key areas of activity – Prevention, Health and Care, and Community building. It will also look to the future to determine how we can redouble global efforts to reduce the overall occurrence of both spina bifida and hydrocephalus across all nations; to establish a basic right to care for all individuals born with these conditions, and to build a stronger, more vocal and effective global community of people united by the challenges of spina bifida and hydrocephalus.
For further information

The National Hereditary Hemorrhagic Telangiectasia Patient & Family Conference
Date: 28-30 October 2016
Venue: Boston, United States of America

The National HHT Patient & Family Conference, which takes place every two years, is an opportunity for Cure HHT to share information with patients and physicians so they can take the initiative to make informed decisions about the treatment and management of HHT.
For further information

Genome Editing for Gene and Cell Therapy, a Herrenhausen Symposium
Date: 3-4 November 2016
Venue: Hanover, Germany

Through talks, a poster session and a panel discussion, the meeting will help identify the scientific, clinical and regulatory hurdles that remain to be overcome. The exchange of ideas and expertise will also help guide the path forward.
For further information

Kennedy's Disease 2016 Conference
Date: 9-11 November 2016
Venue: San Diego, United States

KDA family and researchers join in for indepth presentations on what is working and what isn't quite getting it done. This is a no holds barred discussion that is much appreciated by all the patients and families. Researchers from different labarotories across the globe sit down and compare notes and make presentations to one another on what they are doing.
For further information

Global Summit on Rare Diseases and Orphan Drugs
Date: 15-17 November 2016
Venue: Dubai, United Arab Emirates

The aim of this conference is to bring together bright minds to give talks that are idea‐focused, and on a wide range of subjects, to foster learning, inspiration and wonder – and provoke conversations that matter.
For further information

The Prader Willi Syndrome Association UK national conference 2016
Date: 19-20 November 2016
Venue: Derbyshire, United Kingdom

The conference programme is split into two different age ranges in PWS:
• Birth to 16 years on Saturday
• 16 years and over on Sunday
The programmes for children and adults with PWS will be appropriate to the age group on each day.
For further information

International Primary Immunodefiencies Congress
Date: 8-10 November 2017
Venue: Dubai, United Arab Emirates

For further information

First International SYNGAP1 Conference
Date: 30 November – 1 December 2016
Venue: Texas, United States of America

This conference will utilize a novel multi‐disciplinary approach to bring together patient families, clinicians and researchers as equal stakeholders in order to accelerate research discovery and close the gap to clinical impact.
For further information

3rd IRDiRC conference
Date: 8-9 February 2017
Venue: Paris, France

All stakeholders – active investigators, policy makers, opinion leaders, critical thinkers, young researchers and patient advocates alike – active in the area of rare diseases from across the globe are invited to join us to celebrate achievements in the field, identify future milestones and goals, and work toward bringing diagnoses and therapies to all rare disease patients.
For further information

2017 Rare Disease Day Symposium Alagille Syndrome — New Research, New Hope
Date: 24 February 2017
Venue: La Jolla, United States

The 2017 SBP Rare Disease Day Symposium will focus on Alagille Syndrome, with emphasis on the areas of biliary paucity, genetic mechanism, Notch signaling, and biliary development/regeneration. Scientists, clinicians, advocates, patients and their families are invited to join experts in the ALGS field to foster new perspectives, ideas, and collaborations and accelerate efforts toward a cure for this syndrome.
For further information

7th International Meeting on Pulmonary Rare Diseases and Orphan Drugs
Date: 24-25 February 2017
Venue: Milan, Italy

This meeting will highlight that rare diseases represent an important field of medicine not only for pulmonologists who are skilled in diagnosing and treating particular groups of these illnesses but for all respiratory physicians
For further information

Rare and Undiagnosed Diseases: Discovery and Models of Precision Therapy (C2)
Date: 5-8 March, 2017
Venue: Massachusetts, United States of America

Through this meeting, participants should become familiar with rare and undiagnosed disease programs, acquire insights into new disease mechanisms, learn about potential therapeutic targets, and establish collaborations that enhance rare disorder expertise and new disease discovery. The meeting will bring together physicians who are expert in rare disorders with scientists who know metabolic pathways and mechanisms, advancing understanding and therapy.
For further information

11th European Cytogenetics Conference 2017
Date: 1-4 July 2017
Venue: Florence, Italy

For further information


Commercial events

Orphan Drugs and Rare Diseases
Date: 19-20 October, 2016
Venue: London, United Kingdom

The conference will discuss the latest regulatory developments, explore how to reduce costs and learn from the latest innovations in the orphan drug landscape.
For further information

Drug Developmental Forum
Date: 19-21 September, 2016
Venue: Boston, United States of America

This event will cover the entire drug development process from basic research through clinical trials.
For further information


OrphaNews, The Newsletter of the Rare Diseases Community.
OrphaNews is supported by the European Commission's DG SANTE ( RD-ACTION Joint Action N° 677024) and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Kate Bushby, Ana Rath
Editor: Divya Unni
Editors for Scientific Content: Sophie Höhn
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Editorial Board: Valentina Bottarelli, Victoria Hedley, Yann Le Cam, Stephen Lynn, Charlotte Rodwell, Domenica Taruscio, Ariane Weinmann

Advisory Editorial Board: Ségolène Aymé, Anna Bucsics, Paul Boom, Bruno Dallapiccola, Jordi Llinares-Garcia, Adam Heathfield, Alastair Kent, Dominique Péton-Klein, Milan Macek, Till Voigtländer

Orphanet Partner Country Representatives: Romi Armando (Argentina), Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Micheil Innes (Canada), Ingeborg Barisic (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Sirpa Ala-Mello (Finland), Joerg Schmidtke (Germany), 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), Paul Nogueira (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Luca Lovrecic (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Dorra H'mida (Tunisia), Ugur Ozbek (Turkey), Sarah Stevens (UK)
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