15 September 2015 print
EU Policy News
Nat Pol News
ELS News
New Syndromes
New Genes
Research in Action
Patient Man & Therapy
Orphan Drugs
Partnersearch, Job Opps
Patients' Associations
Courses & Education
What's on?
Media, Press & Publications
Subscribe / Unsubscribe
Search the Orphanews archives :


FDA Guidance document for industry open for public comment

"Rare Diseases: Common Issues in Drug Development" a guidance document recently published by United States Food and Drug Administration (FDA) is now open for public comment

This document aims to assists sponsors of in conducting an efficient and successful developmental programme for orphan drugs and biologics. The document discusses selected issues commonly encountered in rare disease drug development. The FDA addresses the following important aspects of drug development:

Adequate description and understanding of the disease’s natural history
FDA advises sponsors to evaluate existing natural history knowledge of the disease in question early in drug development, to guide clinical development. They recommend that additional data should be collected, preferably prospective data, for a sufficient duration in order to capture "clinically meaningful outcomes and determine variability in the course of the disease."

Adequate understanding of the pathophysiology of the disease and the drug’s proposed mechanism of action
The FDA does not require sponsors to study the biochemical basis of a disease, but necessitates the sponsors to seek an adequate understanding of the pathophysiology at the outset of drug development. The document delineates the aspects of drug development the knowledge will help understand many aspects that is helpful towards drug development which are delineated in the document.

Nonclinical pharmacotoxicology considerations to support the proposed clinical investigation or investigations
FDA stipulated the requirement of "toxicology information from in-vitro studies, animal studies or both before first-in-human use of an investigational drug." Toxicology study design should be based on the biology of the disease, expected pharmacology of the drug, existing Proof-of-Concept (POC) data, clinical trial design or designs to be proposed, and the indication being sought. They ask the sponsors to follow internationally accepted, general guidance’s for the timing and nature of nonclinical safety studies relative to clinical trials in drug development. They instruct drug developers to thoroughly understand the biological relevance and limitations of the animal model of disease if used in nonclinical studies.

Reliable endpoints and outcome assessment
Another important aspect of clinical studies for orphan drugs is the selection of appropriate endpoints. They suggest early development of new assessment tools, or modification of existing ones, before relying upon it as the basis of an endpoint in a clinical trial. Endpoint selection for a clinical trial entails multiple considerations including: an understanding of the disease, including the likelihood, range, and course of clinical manifestations associated with the disease (disease definition). They document also describes the favourable characteristics of the assessment tool to measure suitable endpoints.

Standard of evidence to establish safety and effectiveness
The statutory requirement for marketing approval is “substantial evidence” that the drug will have its claimed effect. To establish this, the sponsors must have an adequate and well-controlled study design, which the FDA has described in the document. FDA stipulates that the sponsor should use “all tests reasonably applicable” and a monitoring plan to establish the safety of the drug for its intended use. According to the document there is no specific minimum number of patients to establish effectiveness and safety of a treatment for any rare disease as it is determined on a case-by-case basis.

Drug manufacturing considerations during drug development
Finally, the document provides guidance on the final facet of drug development as it proceeds to later-phase studies, such as increasing experience with manufacture of the drug, changes in available technology, and the need for larger amounts of the drug in later phases of clinical development which may lead to manufacturing changes that include manufacturing procedures, purification methods, and increased scale. FDA recognises that, especially in the case of orphan drugs, transfer of manufacturing responsibilities could occur after initial testing, which may lead to unanticipated changes to drug characteristics. If significant differences are identified in drug, FDA require these to be addressed and necessary changes be made. To avoid delays, FDA advocate addressing these issues as early as possible.

In all cases the guidance document strongly recommends the sponsors of treatments for rare diseases to start an early dialogue with the FDA in order to avail valuable and productive information to carry forward their trials

Read the document
Deadline for public comment: 30 September 2015

Two resources awarded the IRDiRC Recommended label
IRDiRC recently introduced a quality indicator - “IRDiRC Recommended” which endorses selected tools, standards and guidelines that are of fundamental importance towards rare disease research and development. Additionally, this quality indicator contributes directly to the objectives of IRDiRC :200 new therapies and identify of all genes causing rare diseases by 2020.

The label is provided based on a specific set of criteria. Any resource compliant with the criteria set forth is entitled to the label “IRDiRC Recommended”. It is a public label which guarantee the the resource contributes to ease International collaboration and data sharing, two major objectives of IRDiRC.

Two resources have been recently awarded the “IRDiRC Recommended” label - International Charter of Principles for sharing Bio-Specimens and Data and Orphanet.

International Charter of principles for sharing bio-specimens and data describes best practices on sharing biological data. The charter is the result of careful negotiation of different stakeholder’s - patient representatives, legal experts, ethical experts, industry representatives and scientists - which included a stakeholders workshop held in Brussels in October 2013. The model is built on careful analysis of the discussions of the issues produced during the above meeting as well as on earlier consensus documents and position statements. The five principles for the custodianship of bio-specimen repositories and data - respect for privacy and autonomy, reciprocity, freedom of scientific enquiry, attribution and respect for intellectual property - constitute the common premise for the Charter.

ORPHANET is a free multilingual portal on rare diseases and orphan drugs. It contains information on more than 7000 diseases and aims to improve the quality of medical care and provide specialised services for the rare disease community. Founded in 1997 on the initiative of the French Directorate General for Health and the Inserm (French Institute of Health and Medical Research), Orphanet is today an international project in 36 countries, coordinated in Paris by an Inserm unit. Orphanet aims to help improve the diagnosis, care and treatment of patients with rare diseases, and to provide information on developments in research and new therapies.

IRDIRC invites all project leaders wishing to obtain endorsement by IRDiRC of a platform/tool/standard/guideline that potentially contributes to the acceleration of research and development in the field of rare diseases to apply for the “IRDiRC recommended” label. Commercial products are not eligible.
More information on IRDiRC Recommended


EU Policy News
Fast track routes for medicines that address unmet medical needs
The European Medicines Agency (EMA) has revised its guidelines on the implementation of accelerated assessment and conditional marketing authorisation. Both of these are intended for "innovative medicines that target a disease for which no treatment is available, or that provide patients with a major therapeutic advantage over existing treatments."

The accelerated assessment procedure allows for a faster assessment of eligible medicines by EMA’s scientific committees while Conditional marketing authorisation allows for the early approval of a medicine on the basis of less complete clinical data than normally required, if the medicine addresses an unmet medical need.
More information on the EMA website
The revised guidelines on accelerated assessment and conditional marketing authorization is now open for public consultation which are open until 30 September 2015


National & International Policy Developments
21st Century Act and OPEN Act on incentivising orphan drug development
An article published in ACS Medicinal Chemistry Letters elucidates 2 bills currently being followed in the United States Congress and Senate to promote the development of orphan drugs. These bills are the 21st Century Cures Act (CCA) and Orphan Product Extension Now Accelerating Cures and Treatment Act of 2015 (The OPEN ACT) 1421).

Under the CCA’s OPEN provision, "existing pharmaceutical products would receive a one-time, additional six months of exclusivity for an already-approved drug if the drug’ s sponsor obtains approval of a new indication for the drug for “ a rare disease or condition”." It also provides an Orange Book listed patent, and a generic will not be approved until six months after the expiration of the patent term.

The OPEN ACT, similar to the CCA’ s OPEN provision but currently dead in the senate, would provide for an additional six months of exclusivity for orphan drugs. Again, like the CCA, the OPEN ACT provides an incentive to the innovator by providing an additional six months of exclusivity for the initial indication in return for obtaining approval for treatment of a rare disease or condition.

The authors claim that of the currently pending proposals, the House version of the OPEN ACT, which is now presented to the senate, appears to provide the most incentive to encourage repurposing of existing drug to treat orphan disease.
Read the Open Access article

Other European news
Crossborder Cooperation Opinion adopted by Health Expert Panel

The independent Expert Panel, which advises the European Commission on matters relating to "effective ways of investing in health", has adopted an opinion on Crossborder cooperation. They have identified potential areas for successful cooperation, obstacles to it and priority actions which could be taken at the EU level to overcome these obstacles. The opinion adopted by the expert panel is not binding and is available here

Call for Nominations for the EURORDIS Awards

EURORDIS has announced its fifth edition of the EURORDIS Awards recognising outstanding accomplishments and leading work in the field of rare diseases. The EURORDIS Awards 2016 nomination process is open to everyone to nominate an individual, patient organisation or company you feel merits recognition of their dedication to, or hard work in support of, the rare disease community. For the EURORDIS Awards 2016, you are invited to 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

Visit the EURORDIS website to view previous awardees and read the eligibility criteria. You can use the online nomination form to submit your nomination. The deadline for nominations is 31 October, 2015.

Other International News
CENA approved for $1.2 million in second phase of development of PCORnet, a new national clinical research network
A collaborative, cross‐disciplinary, team led by Genetic Alliance has been approved for a three‐year $1.2 million funding award by the Patient‐Centered Outcomes Research Institute (PCORI) as part of the second phase of PCORnet, the National Patient‐Centered Clinical Research Network. This funding award continues PCORI's support for the Community‐Engaged Network for All (CENA), participation in PCORnet's, a large‐scale collaborative research initiative designed to deeply engage individuals, families and communities to seek the answers relevant to them. PCORnet is a community of patients, their families and caregivers, researchers, scientists, clinicians, health system leaders, and other committed individuals and organizations dedicated to the common purpose of accelerating patient‐centered outcomes research (PCOR).

CENA strives to empower people to accelerate the solutions they need for their lives and the lives of their loved ones. Currently, the eleven organizations that participate in CENA are Alström Syndrome International, AXYS, Celiac Disease Foundation, Dyskeratosis Congenita Outreach, Hepatitis Foundation International, Inflammatory Breast Cancer Research Foundation, Joubert Syndrome and Related Disorders Foundation, LymeDisease.org, MLD Foundation, National Gaucher Foundation, PXE International. They engage their communities, survey members based on the concerns of individuals affected by those conditions, and conduct patient‐centered outcomes research.
Read the press statement by Genetic Alliance

Medicare in the United States to pay more for orphan drug
The current administration of the United States has decided that they (Medicare) will pay for Blincyto - one of the most expensive cancer medications, which costs about USD 178,000 for a standard course of treatment. The decision suggests a new willingness by the government to help pay for promising therapies that are still being evaluated, reversing themselves from previously views on paying for these therapies. Amgen - the producer of Blincyto for patients with a particularly aggressive form of leukaemia sent several pleas including a dossier of scientific evidence, to help the officials to agree that the drug was a substantial improvement over existing treatments for some patients. This move comes after many, including President Obama, expressed concern about high drug prices and their impact on consumers and federal programs.
Read New York Times article on this topic
Read FiercePharma article on this topic

Explanations demanded by policy makers in the United states from companies on drug prices
According to an article published in the New York Times, "pharmaceutical companies are coming under pressure to disclose the development costs and profits of those medicines and the rationale for charging what they do." Lawmakers in the United States have introduced pharmaceutical cost transparency bills in at least six state legislatures in the last year.

The author has also quoted a petition signed by more than 100 prominent oncologists to make drug companies justify their prices, which are often attributed to high research and development costs and contain increases of the prices of cancer drugs. According to the author the United States Senate Finance Committee and the asked Gilead Sciences to disclose cost data of their Hepatitis drug -Sovaldi and the U.A.W. Retiree Medical Benefits asked Vertex Pharmaceuticals, Celgene and other companies report on thier pricing strategy. For the first time ex-Presidents as well as current presidential candidates have also weighed in on this topic asking for "meaningful explanations from the pharmaceutical companies.
Read the open access article

Submissions on the Orphan Drugs Programme in Australia now on the Therapeutic Goods Administration website
The TGA sought comments from interested parties on the Orphan drugs program discussion paper. A total of 30 submissions were received, of which 10 were from pharmaceutical companies, 7 from consumer organisations, 4 from industry organisations and 3 from Government bodies. The remaining 6 submissions were from regulatory affairs organisations, professional bodies and other miscellaneous organisations/individuals.

All submissions that gave permission to be published on the TGA website are now available below in PDF format.
Access the submissions

APARDO: rare disease alliance for the Asia Pacific region
APARDO is the new alliance for the Asia Pacific region and after several years of preliminary work it was formally launched at the Orphan Drugs Congress in Singapore in June 2015. There are many aspects of policy, culture, regulation and levels of development that make it vital for rare disease action plans to be sensitive to and responsive to local and regional issues. APARDO will work to boost rare disease policy and action plans in the region not by trying to “transplant” ideas from the developed health systems, but more by “translating” those ideas and actions into relevant themes for countries in this region. Though APARDO does not yet have a website active, you can read about its development in an article in “An Asia Pacific Alliance for Rare Diseases” published in The Patient.
Read the open access article

Coverage of health policy decisions in Canadian newspapers
A study in the Orphanet Journal of Rare Diseases shows how the Canadian print media reports on issues of access to treatment. The authors demonstrate, through an exhaustive study of the articles published in major newspapers that journalists are more likely to take the view that access to treatment should be provided, sometimes at the expense of evidence. The authors provide compelling and interesting evidence on the nature of bias. Also revealing was that only 23 articles (4.3%) were judged to have a neutral perspective, demonstrating the extent of bias. Access to treatment is an important and often painful issue especially for rare disease patients, and being sympathetic to their cause is natural but this article shows the sizable breadth of this bias.
Read the Open Access article

Offlabel drug use in India: urgent need for regulations
Offlabel of drugs is particularly relevant to patients with a rare disease where sometimes it can be the only available treatment. The author of an article published in Perspectives in Clinical Research describes the risks and benefits to allowing offlabel use of drugs in India. The author asserts that an offlabel use may provide the best available intervention for a patient, especially rare disease patients but may also carry some risks for the patients in case inappropriately utilised, as often the case in India. According to the article, the drug controller general of India (DCGI) is the regulatory authority in India for granting approval for new drugs but, unfortunately, has not produced clearcut guidelines on the offlabel use of drugs. The author believes that the "good reprint practices guidance of FDA could be a good starting point" for DCGI. The authors describes the advantages of offlabel use of drugs making a case for the government, in close association with the DCGI, to look at ways and means to streamline the practice.
Read the Open Access article

Guidance Documents and Recommendations
Sickle cell anemia: guideline on the management of acute chest syndrome
Consult the Pubmed abstract
To read more about "Sickle cell anemia"

Br J Haematol. ; 169(4):492-505 ; May 2015
Dermatofibrosarcoma protuberans: guidelines on diagnosis and treatment
Consult the Pubmed abstract
To read more about "Dermatofibrosarcoma protuberans"

Eur J Cancer. ; S0959-8049(15)00623-1 ; July 2015
Bioinformatics, Registries and Data Management
Phenolyzer adeptly prioritises Mendelian and complex disease genes based on free text phenotype searches
An article published in Nature Methods describes the development of Phenolyzer - a tool that uses prior information to implicate genes involved in diseases. According the authors no tool is able to utilise existing disease nomenclature systems to interpret the user input as free text, which the Phenolyzer is able to produce, exhibiting superior performance over competing methods for prioritising Mendelian and complex disease genes.

The authors first tested Phenolyzer on a small dataset of 14 very well-established Mendelian diseases that are each known to be caused by mutations in only one or two genes and found that Phenolyzer successfully prioritised all disease causal genes as “top1”. Furthermore they evaluated to 590 known inherited disease genes clearly demonstrating that Phenolyzer is adept at finding genes that are known to be associated with Mendelian diseases. The study also demonstrated that Phenolyzer is able to adeptly prioritise candidate genes for complex diseases as well as novel disease genes compared to similar tools.
Read the PubMed abstract

Comparisons of phenotype-driven tools for exome prioritisation tools of human Mendelian disease genes
A review published in Genome Medicine describes prominent exome sequencing projects in the field of rare disease research and tools used for the analysis of variants found in whole exome sequencing data. The authors benchmarked all phenotype-based exome analysis tools on 1000 Genomes Project or in-house exomes which include Phevor, Phen-Gen,eXtasy, PhenIX and Exomiser to "compare and contrast the strengths and weaknesses of current phenotype-driven computational algorithms". The authors believe that the computational phenotype analysis can substantially improve the performance of exome analysis pipelines.
Read the Open Access article

The EuroBioBank Network: its achievements and challenges

An article published in European Journal of Human Genetics has described the EuroBioBank (EBB) network as the "first operating network of biobanks in Europe to provide human DNA, cell and tissue samples as a service to the scientific community conducting research on rare diseases." EURORDIS administered the EBB network from 2003 to 2011 and from 2012, the Fondazione Telethon—partner of TREAT-NMD—took on the responsibility for EBB as a 3-year commitment within the newly established TREAT-NMD Alliance.

The authors describe the EuroBioBank Network Charter, its principles of partnership and conditions of entry for biobanks and biomaterials. The article recounts the achievements, recognitions, publications prepared by EBB and their role in helping the industry towards drug development. Furthermore, the authors highlight their role in fulfilling the objectives of IRDiRC as they provide work and expertise under its umbrella. Finally they also mention that they have to overcome numerous challenges, which include "lack of harmonization; lack of biomaterial and data sharing; lack of recognition; and lack of sustainability.
Read the open access article

GeneMatcher: a matching tool for connecting investigators with an interest in the same gene
GeneMatcher a freely accessible web-based tool developed with the goal of identifying additional individuals with rare phenotypes who had variants in the same candidate disease gene. Described in an article published in Human Mutation it is designed to enable connections between clinicians and researchers with the goal of connecting genes to Mendelian phenotypes and increasing our understanding of these rare disorders. Othe qualities of Gene Matcher is that it does not collect identifiable data and can accept phenotypic data. According to the authors, "since its launch on September 2013, it has collected 2433 individual genes from 539 submitters spread across 49 countries." creating 450 matches encouraging collaborations from various corners of the world. The authors also claim that of the 2178 genes, 307 are related to animal models.
Read the PubMed abstract

Assistive Context Aware Toolkit
Assistive Context Aware Toolkit (ACAT) is an open source platform developed at Intel Labs, initially for Prof. Stephen Hawking, through an iterative process to enable people with disabilities to "easily communicate with others through keyboard simulation, word prediction and speech synthesis." The software helps the users to perform a variety of tasks (editing, managing documents and email accounts, navigating the Web) with ease.

Apart from being useful for the development of assistive technologies it is also advantageous for researchers working on "new user interfaces, new sensing modalities or word prediction and wanting to explore these innovations in the this community."
Access the ACAT website

Screening and Testing
Targeted next generation sequencing for clinical diagnosis of 561 mendelian diseases
The authors of a study published in PLOS One designed a "capture array for all the coding sequence of 2,181 genes associated with 561 Mendelian diseases and conducted next generation sequencing to detect mutations." Results of the evaluation showed that their method had high accuracy and stability in detecting disease causing mutations. The authors believe that this technology can be used for "diagnostic testing, providing effective basis for the clinical diagnosis or genetic counseling of 561 Mendelian diseases." The article provides a list of the Mendelian diseases analysed in this study in their supplementary materials.
Read the open access article


Ethical, Legal & Social Issues
Face2Gene calls for pilot sites to pursue research programme
Face2Gene a genetic search and reference solution powered by FDNA (Facial Dysmorphology Novel Analysis) technology facilitates the detection of facial dysmorphic features and recognisable patterns of human malformations to present comprehensive and up-to-date genetic references. They are now inviting institutions to pilot the Face2Gene Academy to teach healthcare professionals specializing in genetics the “ART OF DYSMORPHOLOGY” and to join the pilot research programme - "GIVE A FACE TO A SYNDROME".

Face2Gene technology leverages advanced algorithms and the cumulative experience of genetics professionals and analyzed cases. It improves over time, referencing comprehensive phenotype databases in real-time, accelerating and increasing confidence in the research and investigation of genetic syndromes. Through the pilot programme you can use the Facial Dysmorphology Novel Analysis technology for free, leverage the support of a dedicated research team and utilise FDNA’s tens of thousands of dysmorphology related data‐points to analyze your research sample.
Visit the FDNA website

Compassionate use of orphan drugs
An article published in Orphanet Journal of Rare Diseases provides several justifications for the provision of compassionate usage of drugs in the European Union (EU). In the EU drug developers are allowed to provide drugs to patients drugs on compassionate grounds, over a specific period of time while awaiting marketing authorization. Although it depends on the pharmaceutical companies and the member state on whether the drugs will be provided under these conditions, the authors gives many reasons why it is a beneficial opportunity for the company. These include fitting into corporate social responsibility programmes, the provision of invaluable clinical data particularly in rare diseases, rapid access to possible reimbursement options, preference of a company to donate a drug rather than sell at a discounted rate to individual countries, establish an early market presence in affluent countries and establishing good will. Further, the authors discuss legal mechanisms and ethical arguments to encourage compassionate use.
Read the open access article

The success of crowdfunding campaigns
A short study conducted by authors of an article published in The Lancet shows that crowdfunding - funding directly from the public through the internet - might represent a valuable avenue to finance randomised control trials (RCT). The authors assessed the success rate of the top online (based on site volume) English crowdfunding websites. Their results demonstrate that most crowdfunding projects reached their target, in fact even unsuccessful campaigns were able to raise some funds, albeit a small percentage of their target goal. According to the authors this strategy might be "especially useful for pilot or phase 1 studies because funding from national public agencies is insufficient."
Read the open access article

Information for neonatal nurses on rare diseases
An editorial in the journal Advances in Neonatal care advises neonatal nurses on caring for infants with rare diseases (RDs). The author points out that every neonatal nurse has taken care of infants with RDs and will take care of many more in the course of his or her career. She asks nurses to include a systematic approach to the evaluation of the neonate who presents with symptoms consistent with an RD. Clear communication is vital to prevent misunderstanding, confusion, and false hopes on the part of the parents. Equally important is handling the parents with skill and sensitivity while helping parents to find the best treatment and sift through available information. The author advises neonatal caregivers to become familiar with NORD (the National Organization for Rare Diseases; http://www.rarediseases.org/), as a reliable starting point for both parents and healthcare professionals to learn about RDs.
Read the open access article

Locked-in syndrome display a satifactory quality of life
A study published in Orphanet Journal of Rare Diseases performed a survey of a population of locked-in syndrome (LIS) patients to describe the course of the quality of life (QoL) of these patients over a 6-year period and to determine the potential predictive factors of QoL changes over time. They recorded socio-demographic data, clinical data related to LIS, physical/handicap status, psychological status, self-reported QoL, and integration in life. The study demonstrated that the QoL of the patients was relatively satisfactory compared to populations in other severe conditions over the 6 year period studied. According to the authors “preservation of autonomy and communication may help them to live as normal life as possible.”
Read the open access article

Orphan drug developers scramble for clinical trial patients
After years of efforts, scientists and families of young patients with the genetic condition Niemann-Pick Type C (NPC) are in a position to which any rare disease community aspires: the prospect of not one but three companies launching clinical trials to develop therapies. United States startup Vtesse, CTD Holdings, and Danish startup Orphazyme are developing therapies for NPC, but there are only about 500 known cases of the disease worldwide due to which they must compete with one another to get access to these communities. It’s hard to find a sufficient patient population to test their drugs, questioning the ability of the rare disease community to support more than one clinical trial at a time without siphoning participants from each other.
Read the article in The Washington Post


New Syndromes

Novel disorder of congenital insensitivity to pain, inability to feel touch and cognitive delay due to homozygous missense mutation in CLTCL1
The authors reported a novel recessive disorder characterised by congenital insensitivity to pain, inability to feel touch, and cognitive delay in a consanguineous family of Balochi origin. Affected individuals harboured a homozygous missense mutation in CLTCL1.
Consult the Pubmed abstract

Brain ; 138(Pt 8):2147-60 ; August 2015
Autosomal dominant small vessel disease associated with heterozygous HTRA1 mutations
The authors used whole exome sequencing to identify candidate genes in an autosomal dominant small vessel disease family of unknown aetiology. A heterozygous HTRA1 was identified in all affected members. Clinical features of this autosomal dominant small vessel disease differ from those of CARASIL and CADASIL by a later age of onset and the absence of the typical extra-neurological features of CARASIL. They are similar to those of sporadic small vessel disease, except for their familial nature.
Consult the Pubmed abstract

Brain ; 138(Pt 8):2347-58 ; August 2015
Novel 12q12 deletion syndrome which could be caused by ANO6, NELL2 and DBX2 haploinsufficiency
The authors report on a 10 year old boy presenting with moderate intellectual disability, impaired motor skills, hypotonia, growth delay, minor anomalies, misaligned teeth, pectus excavatum, small hands and feet, widely spaced nipples, and a 12q12 deletion deleting ANO6, NELL2 and DBX2 genes. This deletion is included in the deletion carried by four previously reported patients. The clinical presentation of these patients points to the recurrence of the following manifestation, possibly delineating a 12q12 deletion syndrome phenotype: moderate to severe developmental/intellectual delay, hypotonia, postnatal growth retardation, skeletal and dental anomalies, minor facial anomalies including strabismus, down slanting palpebral fissures, and large/low-set ears.
Consult the Pubmed abstract

Am J Med Genet A. ; 167(8):1890-6 ; August 2015
Microdeletion 1p35.2: a recognizable facial phenotype with developmental delay which could be linked to HDAC1 mutation
The authors described two patients with microdeletion 1p35.2, intrauterine growth retardation, small stature, hypermetropia, hearing impairment and developmental delay. Both patients have long, myopathic facies, with fine eyebrows, small mouths and micrognathia. They postulated a role for HDAC1 gene in the facial phenotype.
Consult the Pubmed abstract

Am J Med Genet A. ; 167(8):1916-20 ; August 2015
A novel maternally inherited 8q24.3 deletion in two siblings
The authors reported on a 7 year old female with developmental delay, autism spectrum disorder, intellectual disability, attention deficit hyperactivity disorder, and seizures. Oligomicroarray analysis revealed a microdeletion in the chromosome 8q24.3 region. Two siblings of the proband were also analyzed. The proband's older brother presented the same phenotype and had both 8q24.3 and 14q23.3 deletions. Parental FISH analysis indicated that the mother was a carrier for the 8q24.3 deletion and the father was a carrier for the 14q23.3 deletion. The 8q24.3 deletion seen in these patients had not been reported in the literature.
Consult the Pubmed abstract

Am J Med Genet A. ; 167(8):1921-6 ; August 2015
New malformation syndrome with intellectual disability, unique facial dysmorphism, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK
The authors reported a new syndrome due to loss-of-function variants in HNRNPK in two probands. Both probands have intellectual disability, a shared unique craniofacial phenotype, and connective tissue and skeletal abnormalities. Additionally, two individuals with deletions of 9q21 encompassing HNRNPK have been recently reported in the literature with phenotypes that significantly overlap with these probands, lending further support that haploinsufficiency of HNRNPK leads to a congenital malformation syndrome associated with intellectual disability.
Consult the Pubmed abstract

Hum Mutat. ; [Epub ahead of print] ; July 2015

New Genes

X-linked syndromic intellectual disability caused by a missense mutation in RPL10 in a large family
Consult the Pubmed abstract
To read more about "X-linked syndromic intellectual disability"

Am J Med Genet A. ; 167(8):1908-12 ; August 2015
Inherited peripheral neuropathies due to loss of function mutations in HARS
Consult the Pubmed abstract
Brain ; 138(Pt 8):2161-72 ; August 2015
Campomelic dysplasia linked to MAP2K6 in a patient
Consult the Pubmed abstract
To read more about "Campomelic dysplasia"

Am J Med Genet A ; 167(8):1842-50 ; August 2015
Cutis marmorata telangiectatica congenital might be caused by a homozygous truncating mutation of ARL6IP6
Consult the Pubmed abstract
To read more about "Cutis marmorata telangiectatica congenita"

Hum Genet. ; 134(8):815-22 ; August 2015
Familial abdominal aortic aneurysm: MYH11 as a candidate gene
Consult the Pubmed abstract
To read more about "Familial abdominal aortic aneurysm"

Hum Genet. ; 134(8):881-93 ; August 2015

Research in Action

Clinical Research
Cystic fibrosis: lumacaftor in combination with ivacaftor provides a benefit for patients homozygous for the Phe508del CFTR mutation
Consult the Pubmed abstract
Consult the French TRAFFIC study on Orphanet
Consult the French TRANSPORT study on Orphanet
Consult the Spanish study on Orphanet

To read more about "Cystic fibrosis"

N Engl J Med. ; 373(3):220-31 ; July 2015
Erythropoietic protoporphyria: increased duration of sun exposure without pain and improved quality of life with afamelanotide
Consult the Pubmed abstract
To read more about "Autosomal erythropoietic protoporphyria"

N Engl J Med. ; 373(1):48-59 ; July 2015
Neuromyelitis optica: prolonged tocilizumab therapy may be safe and effective
Consult the Pubmed abstract
To read more about "Neuromyelitis optica"

JAMA Neurol. ; 72(7):756-63 ; July 2015
Myasthenia gravis: tapering mycophenolate mofetil appears safe after years of disease stability
Consult the Pubmed abstract
To read more about "Myasthenia gravis"

Muscle Nerve ; 52(2):211-5 ; August 2015
Spinal muscular atrophy type III: mitigated results with 12 weeks of cycle ergometer training
Consult the Pubmed abstract
To read more about "Proximal spinal muscular atrophy type 3"

Muscle Nerve ; 52(2):240-4 ; August 2015
Enthesitis-related arthritis: efficacy and safety of etanercept
Consult the Pubmed abstract
To read more about "Enthesitis-related arthritis"

Arthritis Rheumatol. ; 67(8):2240-9 ; May 2015
Malaria: DSM265, an inhibitor of dihydroorotate dehydrogenase, as a potential drug to treat the patients
Consult the Pubmed abstract
To read more about "Malaria"

Sci Transl Med. ; 7(296):296ra111 ; July 2015
Immune thrombocytopenic purpura: efficacy and safety of a triple therapy using dexamethasone, rituximab, and cyclosporine
Consult the Pubmed abstract
To read more about "Immune thrombocytopenic purpura"

Blood ; 126(4):500-3 ; July 2015
T-cell lymphoma: everolimus has antitumour activity
Consult the Pubmed abstract
Blood ; 126(3):328-35 ; July 2015
Acute myeloid leukemia: azacitidine may be an important treatment option in older patients
Consult the Pubmed abstract
Consult the Belgian study on Orphanet
Consult the Spanish study on Orphanet
Consult the French study on Orphanet

To read more about "Acute myeloid leukemia"

Blood ; 126(3):291-9 ; July 2015
Trisomy 18 and trisomy 13: description of 22 children
Consult the Pubmed abstract
To read more about "Trisomy 18"
To read more about "Trisomy 13"

Am J Med Genet A. ; 167(8):1807-15 ; August 2015
Autologous hematopoietic stem cell transplantation: 10 years of data from Pakistan
Consult the Pubmed abstract
To read more about "Lymphoma"
To read more about "Multiple myeloma"

Stem Cells Transl Med. ; 4(8):873-7 ; August 2015
Noonan syndrome-like disorder with loose anagen hair could be a tumour predisposing syndrome
Consult the Pubmed abstract
To read more about "Noonan syndrome-like disorder with loose anagen hair"

Am J Med Genet A. ; 167(8):1902-7 ; August 2015
Therapeutic Approaches

Sickle cell anemia: the LSD1 inhibitor RN-1 induces fetal hemoglobin synthesis and reduces disease pathology in mice
Consult the Pubmed abstract
To read more about "Sickle cell anemia"

Blood ; 126(3):386-96 ; July 2015
Glycogen storage disease due to acid maltase deficiency: early restoration of alpha-glucosidase activity with gene therapy is most effective than late correction
Consult the Pubmed abstract
To read more about "Glycogen storage disease due to acid maltase deficiency"

Ann Neurol. ; 78(2):222-34 ; August 2015
X-linked Charcot-Marie-Tooth disease type 1: intraneural GJB1 gene delivery improves nerve pathology in a mouse model
Consult the Pubmed abstract
To read more about "X-linked Charcot-Marie-Tooth disease type 1"

Ann Neurol. ; 78(2):303-16 ; August 2015
Acute graft versus host disease: treatment with agonistic DR3 antibody reduces the disease
Consult the Pubmed abstract
To read more about "Acute graft versus host disease"

Blood ; 126(4):546-57 ; July 2015
Stargardt disease: rescue of the phenotype in Abca4 knockout mice through inhibition of vitamin A dimerisation
Consult the Pubmed abstract
To read more about "Stargardt disease"

Proc Natl Acad Sci U S A. ; 112(27):8415-20 ; July 2015
Marburg hemorrhagic fever: on the basis of efficacy in nonhuman primates, AVI-7288, a phosphorodiamidate morpholino oligomer, has potential as postexposure prophylaxis in humans
Consult the Pubmed abstract
To read more about "Marburg hemorrhagic fever"

N Engl J Med. ; 373(4):339-48 ; July 2015
Diagnostic Approaches

Neuromyelitis optica spectrum disorders: review on advanced magnetic resonance imaging techniques
Consult the Pubmed abstract
To read more about "Neuromyelitis optica"

JAMA Neurol. ; 72(7):815-22 ; July 2015
Limb-girdle muscular dystrophy type 2A: review on protein and genetic diagnosis
Consult the Pubmed abstract
To read more about "Autosomal recessive limb-girdle muscular dystrophy type 2A"

Muscle Nerve ; 52(2):163-73 ; August 2015
Giant cell arteritis: review on imaging
Consult the Pubmed abstract
To read more about "Giant cell arteritis"

Curr Rheumatol Rep. ; 17(8):527 ; August 2015
Disorders of sex development: review on molecular diagnosis
Consult the Pubmed abstract
Nat Rev Endocrinol. ; 11(8):478-88 ; August 2015
Chronic myelomonocytic leukemia: evidence for using flow cytometric immunophenotyping as an ancillary diagnostic test
Consult the Pubmed abstract
To read more about "Chronic myelomonocytic leukemia"

Eur J Haematol. ; 95(2):168-76 ; August 2015

Patient Management and Therapy
Multiple myeloma: review on therapies
Consult the Pubmed abstract
To read more about "Multiple myeloma"

Blood ; 126(3):300-10 ; July 2015
Sickle cell anemia: review on pathophysiology and management of the acute vaso-occlusive crisis
Consult the Pubmed abstract
To read more about "Sickle cell anemia"

Eur J Haematol. ; 95(2):113-23 ; August 2015
Bilateral striopallidodentate calcinosis: a review
Consult the abstract
To read more about "Bilateral striopallidodentate calcinosis"

Orphan Drugs: Research and Reviews ; 2015(5):43-49 ; July 2015
Mast cells, mastocytosis and related disorders: a review
Consult the Pubmed abstract
N Engl J Med. ; 373(2):163-72 ; July 2015
Femur-fibula-ulna complex and fibular hemimelia: a review
Consult the Pubmed abstract
To read more about "Femur-fibula-ulna complex"
To read more about "Fibular hemimelia"

Radiographics ; 35(4):1191-207 ; August 2015
Congenital hypothyroidism: a review
Consult the abstract
To read more about "Congenital hypothyroidism"

Orphan Drugs: Research and Reviews ; 2015(5):91-102 ; July 2015
Transfusion-associated graft versus host disease: a review
Consult the Pubmed abstract
To read more about "Graft versus host disease"

Blood ; 126(3):406-14 ; July 2015
Cortical superficial siderosis: review on detection and clinical significance
Consult the Pubmed abstract
To read more about "Superficial siderosis"

Brain ; 138(Pt 8):2126-39 ; August 2015
Myasthenia: a review
Consult the Pubmed abstract
To read more about "Myasthenia gravis"
To read more about "Congenital myasthenic syndrome"

JAMA Neurol. ; 72(7):812-4 ; July 2015
Remitting seronegative symmetrical synovitis with pitting edema or RS3PE: a review
Consult the Pubmed abstract
Curr Rheumatol Rep. ; 17(8):525 ; August 2015
Acute myeloid leukemia in the pregnant patient: a review
Consult the Pubmed abstract
To read more about "Acute myeloid leukemia"

Eur J Haematol. ; [Epub ahead of print] ; February 2016
B-cell chronic lymphocytic leukemia: five reviews
Consult the Pubmed abstracts
To read more about "B-cell chronic lymphocytic leukemia"

Blood ; 126(4):445-53; 454-62; 463-70; 471-77; 478-85 ; July 2015
Pancreatic neuroendocrine tumours in patients with multiple endocrine neoplasia type 1: review on the management
Consult the Pubmed abstract
To read more about "Pancreatic endocrine tumor"
To read more about "Multiple endocrine neoplasia type 1"

Lancet Diabetes Endocrinol. ; [Epub ahead of print] ; July 2015
Adolescent and young adult patients with cancer: a review
Consult the Pubmed abstract
Nat Rev Clin Oncol. ; 12(8):465-80 ; August 2015
Five 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. Five updated GeneReviews have been published for:
15q13.3 microdeletion
EFEMP2-related cutis laxa
MYH9-related disorders
Timothy syndrome


Orphan Drugs
Regulatory News
FDA extends use of Promacta in young children with rare blood disorder

The U.S. Food and Drug Administration approved Promacta (eltrombopag) to treat low blood platelet count in paediatric patients – ages one year and older – with a rare blood disorder called chronic immune thrombocytopenic purpura (ITP). Promacta can be used in these children when they have not achieved an appropriate response using other ITP medicines or surgery to remove the spleen.

ITP is a disorder that results in an abnormally low number of platelets, the cells that help your blood clot. Without enough platelets, bleeding can occur under the skin, in mucous membranes (such as in the mouth) or in other parts of the body. Promacta helps increase blood platelet production and is available as a tablet taken once daily or as a powder that is mixed with liquid for children ages one to five to take orally. It was first approved in 2008 to treat adult patients with the same condition as the new paediatric indication.
Read the FDA press release

Breakthrough Therapy Designation: a review
An article in Clinical Therapeutics has reviewed the regulatory pathways made available by the US Food and Drug Administration (FDA) to expedite the drug development and approval process, with a focus on the benefits and limitations of the Breakthrough Therapy Designation (BTD) pathway. The authors highlight that the ultimate goal of the BTD program is to identify promising drug candidates early in the clinical development timeline, expedite the development and review processes via intensive guidance from the FDA, and provide patients access to approved therapies as quickly as possible. The paper differentiates BTD from Fast Track Designations (FTD) as requiring more stringent evidence to qualify. It notes that BTD has been far more successful than anticipated and has had a significant impact on stakeholders. Criticisms include that the minimum “bar” for BTD approval remains unclear for both the sponsor and other stakeholders.
Read the PubMed abstract

Positive opinions recommending orphan designation at the COMP meeting
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted twenty one positive opinions issued at the June 2015 COMP meeting for :

- treatment of avian influenza
- treatment of hepatoblastoma
- treatment of plasminogen deficiency
- treatment of autosomal dominant polycystic kidney disease
- treatment of cutaneous T-cell lymphoma
- treatment of acute myeloid leukaemia
- treatment of retinitis pigmentosa
- treatment of Duchenne muscular dystrophy
- treatment of malaria
- treatment of craniopharyngioma
- treatment of perinatal asphyxia
- treatment of fragile X syndrome
- treatment of progressive supranuclear palsy
- treatment of amyotrophic lateral sclerosis
- treatment of acute myeloid leukaemia
- treatment of pancreatic cancer
- treatment of Rett syndrome
- treatment of primary hyperoxaluria
- treatment of carnitine palmitoyltransferase II deficiency
- treatment of long-chain 3-hydroxyacyl-coA dehydrogenase deficiency
- treatment of mitochondrial trifunctional protein deficiency

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

- treatment of Rett syndrome
- treatment of osteogenesis imperfecta
- treatment of short bowel syndrome
- treatment of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
- treatment of hepatocellular carcinoma
- treatment of diffuse large B-cell lymphoma
- treatment of X linked myotubular myopathy
- treatment of mucopolysaccharidosis type II (Hunter's syndrome)
- treatment of acute lymphoblastic leukaemia
- treatment of acute myeloid leukaemia
- treatment of acute radiation syndrome
- 2 treatments for cystic fibrosis
- treatment of marginal zone lymphoma
- treatment of congenital adrenal hyperplasia

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

- treatment of mantle cell lymphoma
- treatment of primary mediastinal large B-cell lymphoma
- treatment of aneurysmal subarachnoid haemorrhage
- treatment of snakebite envenomation
- treatment of hereditary angioedema
- treatment of chronic iron overload requiring chelation therapy
- treatment of primary graft dysfunction
- treatment of systemic sclerosis
- treatment of hepatocellular carcinoma
- treatment of idiopathic pulmonary fibrosis
- treatment of immune thrombocytopenia
- treatment of aniridia
- treatment of glioma
- treatment of narcolepsy
- treatment of Duchenne muscular dystrophy
- treatment of achromatopsia
- treatment of acute myeloid leukaemia
- treatment of tuberous sclerosis
- Three chimeric human/murine monoclonal antibodies against the Ebola (Zaire) surface glycoprotein for treatment for Ebola virus disease

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
Patient-Funded Trials: Opportunity or Liability?
A review on patient funded trials published in Cell Stem Cell argues that patient-funded trials in its current form needs reform. Patient-funded trials (PFTs), refers to studies funded directly by patients seeking to enrol in trials as participants. The author believes that "left unchecked, these interests can threaten the ability of research to advance biomedical progress." In PFTs, patient sponsors are strongly motivated by the short-term goal of access to new interventions and the profit motive shifts from the sponsor to PFT clinics, which generate revenue directly from the enrolment of participants increasing patient exposure to the risks of unproven interventions. The result is the ability of unscrupulous clinics to co-opt the ‘‘therapeutic hope’’ of desperate patients to sell them access to ‘‘trials’’ of interventions with little or no scientific foundation. They also point out that many utilise trial designs which are notoriously unreliable. The authors provide some key recommendations to policy makers to improve the situation for PFT such as a creating a mechanism for scientific and ethical oversight of PFTs and consider whether accreditation requirements for health care facilities could be used to encourage entities conducting PFTs.
Access the article

Drug mechanisms with genetic support observe greater success in all phases of drug development
An article produced in Nature Genetics provides guidance on the weight that should be given to genetic evidence in predicting drug mechanisms by investigating the current archive. To broadly capture statistically significant common variant genetic associations, the authors used GWASdb10, which combines data from multiple sources. They manually mapped all traits to the most specific Medical Subject Heading (MeSH) terms applicable to compare among all data sources and derived genes involved in rare, mende¬lian traits from Online Mendelian Inheritance in Man (OMIM). The study sought information about drugs across the various stages of development was drawn from the commercial Informa Pharmaprojects database.

After analysing the overlap between drug targets and their indications with genetic associations for similar traits the authors found that (the) "genetic support increased from 2.0% for target-indication pairs that had only progressed as far as phase I clinical trials to 8.2% for approved drugs." This substantial increase, according to the authors demonstrate that the "odds of successful drug mechanisms with genetic support are many times greater than without." Thus the authors estimate that "drug mechanisms with genetic support would succeed twice as often as those without it (from phase I to approval)."
Read the PubMed abstract

Report of the ISPOR Rare Disease Special Interest Group on definitions and terminology for rare diseases
In June 2013, the Rare Disease Terminology & Definitions Used in Outcomes Research Working Group was established under the auspices of the ISPOR Rare Disease Special Interest Group. Members developed the concept because of the lack of a universal definition of rare diseases or the technologies used in their treatments and the existing diversity in the use of different definitions used to describe rare diseases and the underlying connotations associated with them.

Authors of an article published in Value in Health describe how ISPOR systematically searched for definitions related to rare disease from organisations in international jurisdictions utilising descriptive statistics of definitions and calculating prevalence thresholds. The group identified 296 definitions from 1109 organizations. They observed that the terms rare diseases and orphan drugs were used most frequently as identifiers along with a prevalence threshold. They also observed that genetics was infrequently used as an identifier. The authors believe that these findings highlight that "attempts to harmonise rare disease definitions should focus on standardising objective criteria such as prevalence thresholds and avoid qualitative descriptors."
Access the article

Cost-effectiveness and cost-utility of ultraorphan drugs in Europe

Drugs for ultra-orphan diseases are amongst the most expensive medicines on a cost-per-patient basis. The extremely high prices have prompted initiatives to evaluate cost-effectiveness and cost-utility in EU-member states. A review presented in the Orphanet Journal of Rare Diseases was to evaluate the quality of cost-effectiveness and cost-utility studies on ultra-orphan drugs. The authors assessed the economic evaluations ultra-orphan drugs marketed in the EU that have been performed so far with specific focus on the methods used and the quality of the studies. The study shows that the choice of which type of economic model to use is dependent on the type of disease that is described, the amount of data available, but also on the time and experience of the researcher. However, the authors also demonstrate that considering the need for modelling of several disease states and the small patient groups, a Markov-state-transition model seems to be most suitable type of model even though ultra-orphan drugs will usually not meet the conventional criteria for cost-effectiveness.
Read the open access article



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

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

BMBF Funding initiative: innovative stem cell technologies for personalized medicine
The German Federal Ministry for Education and Research (BMBF) has announced a new funding initiative for the development and use of innovative stem cell technologies. The initiative aims at funding interdisciplinary research collaborations which are geared towards unlocking the full potential of novel reprogramming technologies and iPS cells for practical use. For this, a pooling of expertise from applied basic and clinical research is needed, for example of research groups from the life sciences, medicine, pharmacology and relevant technical disciplines. The funding can be applied for in two modules: "therapy" and "model & test systems". Deadline for applications is 30 November 2015.
More information (in German)

8th Call for SMA research proposals
This Call is open to any research project aimed at finding a therapy for Spinal Muscular Atrophy (SMA) or elucidating the basic pathophysiological processes of the disease. SMA‐Europe aims to help the international scientific and medical community in its search for therapies for SMA. Preferences will be given to projects with the greatest potential to overcome barriers to translate science into effective treatments.
Two types of research grants will be awarded for up to two years:
1. Operating Grants
2. Postdoctoral Fellowship
Application deadline: 9 December 2015
For further information

Partnersearch, Job Opportunities
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

Civil Society representatives: Call for expression of interest is open for the EMA Management Board
The Commission is launching a selection procedure to appoint the Civil Society representatives in the Management Board of the European Medicines Agency (EMA), in London. Four members from Civil Society will be appointed: two members representing patients’ organisations, one member representing doctors’ organisations and one member representing veterinarians’ organisations. The term of office of the current members expires on 20 March 2016.
For further information

ERN ASSESSMENT: Call for Tender for Independent Assessment Bodies
A Call for tender concerning the selection of the independent assessment/evaluation bodies in charge of the assessment of the applications of Network and membership proposals has been launched on 22 July, 2015.

The purpose of this call for tender is to conclude Multiple Framework Contracts with reopening of competition with Independent Assessment Bodies capable of performing the technical assessment of European Reference Network(s) proposals and healthcare provider's applications under the framework of Article 12 of Directive 2011/24/EU on patients' rights in cross-border healthcare.
Deadline: 29 September 2015
You will find all the information related with the application and content of the call in
For further information


News from the Patients' Associations
24 September observed as aHUS Awareness Day to raise visibility
Atypical Hemolytic Uremic Syndrome is a life-threatening disease characterised by the systemic formation of blood clots throughout the body potentially causing damage to the kidneys and other organs, with complications that may include serious or fatal events including stroke, cardiac issues, and kidney failure. It affects both adults and children and is often associated with an uncontrolled activation of the complement system, part of the body's protective immune system. The aHUS Alliance, a confederation of 14 nations with atypical HUS patient organisations, has announced plans for a global awareness campaign on 24 September 2015. The theme for aHUS Awareness Day is 'Communication' to support aHUS patients and their families, discuss and address common concerns, and improve access to drugs and therapies that can save lives and improve outcomes.
For more information visit the aHUS alliance website


Courses & Educational Initiatives

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 further 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 further 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

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.
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 further information


What's on Where?

European Association of Centres of Medical Ethics Conference
Date: 17 -19 September, 2015
Venue: Cagliari, Italy

For further information

The Canadian Organization for Rare Disorders Annual General Meeting
Date: 22 September, 2015
Venue: Teleconference

All individual, affiliate and corporate members of CORD in good standing are invited participate at the Annual General Meeting.
For further information

UMIB Summit 2015
Date: 24-25 September, 2015
Venue: Porto, Portugal

The UMIB Summit 2015 aims at gathering national and foreign researchers working in clinical research and clinically-oriented basic research, who present their research lines, promote the exchange of work experiences and establish synergies that allow the creation of international consortia for the implementation of strategic projects in the field of biomedicine.
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

Orphan Drugs Patient Access
Date: 23 September, 2015
Venue: Online Conference

In this online conference you can learn how businesses can collaborate with patient groups and communities to foster research, development and market access for orphan drugs. You can also hear about building a collaborative model where all stakeholders are engaged. It gives you an opportunity to discuss how business strategies can help work with patient organizations, bring crucial insights on the importance of patients in research which are often overlooked and clarify what the EU platform for rare disease registries will offer.
For further information

4th Annual Wolfram Syndrome Information & Support Day Invitation
Date: 24 September, 2015
Venue: Washington, USA

You will have the chance to speak to experts on Wolfram Syndrome, hear about the latest research and meet families/individuals affected by the condition.
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

4th World Congress of Clinical Safety
Date: 28- 30 September, 2015
Venue: Vienna, Austria

This Vienna Congress is organised by IARMM to improve and promote high advanced safe and clean science and technology in both risk and crisis management and governance. The congress covers a wide range of topics such as patient safety, medication safety, infectious disease outbreak, and other related subjects.
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

The 7th International Symposium on Myelodysplastic syndromes, JMML, and Bone Marrow Failure Syndromes
Date: 1 – 3 October, 2015
Venue: Aarhus, Denmark

The symposium will share and discuss the latest news about bone marrow failure, myelodysplastic, and myeloproliferative diseases.
For further information

3rd ESPT Conference
Date: 7 – 9 October, 2015
Venue: Budapest, Hungary

The main objective of the conference is to improve and accelerate Clinical Implementation of Pharmacogenomics and Personalized Medicine. The meeting will bring together laboratory medicine specialists, pharmacologists, clinicians, scientists from pharmaceutical and biotechnological industries, geneticists, hospital pharmacists and epidemiologists from Hungary, the nearest countries and overall Europe.
For further information

9th Annual Sickle Cell and Thalassaemia Advanced Conference
Date: 7 – 9 October, 2015
Venue: London, UK

This annual conference is now in its 9th year and is well established as one of the leading events in the world, providing an international forum for dialogue and interaction between the leading world experts in Sickle Cell Disease (SCD) and Thalassaemia and health care professionals at the frontline of care.
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

ECD Global Alliance Patient and Family Gathering
Date: 8-10 October, 2015
Venue: Texas, USA

The gathering includes dinner for medical professionals and patients/families, patient and family gathering and a challenge celebration.
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

6th South Eastern European Cystic Fibrosis Conference
Date: 19-20 October, 2015
Venue: Bucharest, Romania

This regional conference is a 2‐day symposium in Romania, addressing physicians, allied health professionals and patient representatives from the South Eastern European and Mediterranean region.
For further information

13th Annual Congress Of International Drug Discovery Science & Technology, Therapy And Expo‐2015
Date: 20-22 October, 2015
Venue: Beijing, China

This conference will provide a unique opportunity for researchers from all over the world to meet, network, and forge new scientific interactions.
For further information

The BioData World Congress 2015
Date: 21-22 October, 2015
Venue: Cambridge, United Kingdom

This conference is held with the support of Intel, The Wellcome Trust Sanger Institute, The European Bioinformatics Institute, The Babraham Institute, BIA, BioNow, The Pharmacogenetics and Stratified Medicine Network and the Pistoia Alliance, BioData World Congress.
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

Sixth Croatian Congress of Human Genetics
Date: 5-7 November, 2015
Venue: Zagreb, Croatia

This conference will be an opportunity for education of the young interested in new achievements in various areas of genetics – clinical genetics, cytogenetics, molecular genetics and anthropology, and also to highlight the importance of prevention, diagnostics and treatment of rare diseases.
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

Statistical analysis of massive genomic data
Date: 19-20 November, 2015
Venue: Evry, France

This two-day cross-disciplinary conference will bring together biologists, geneticists, clinicians, bioinformaticians and statisticians in order to discuss emerging challenges raised by the analysis of high-throughput genomic data, and present dedicated innovative approaches.
For further information

6th European Symposium on rare anaemias - 1st Dutch-Belgian meeting for patients and health professionals
Date: 21-22 November, 2015
Venue: Amsterdam, The Netherlands

The 6th European Symposium on Rare Anaemias is an activity of the ENERCA project which aims to disseminate up-to-date knowledge and increase the public awareness about congenital and rare anaemias. This year, transversal topics centered on common medical problems of patients with sickle cell, thalassaemia and other forms of haemolytic anaemia will be one of the key points of the symposium.
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

Clinical Innovation & Outsourcing
Date: 9-10 March, 2016
Venue: London, UK

Clinical Outsourcing & Partnering World is the largest industry event focusing on the strategic and operational considerations in clinical outsourcing. It is a place where serious business contacts are made. Attended by senior decision makers, it's a platform which facilitates meetings between your sales force and prospects and it's a cost effective sponsorship package with year round advantage.
For further information

MYOLOGY 2016 Fifth International Congress of Myology
Date: 14-18 March, 2016
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

9th ISNS International meeting/10th ISNS European Regional meeting
Date: 11-14 September, 2016
Venue: The Hague, the Netherlands

The conference will aid the sharing of neonatal screening experiences for congenital metabolic disorders, its clinical diagnostics and follow-up, and will facilitate learning from other experiences. The programme will consist of plenary lectures, oral presentations and poster sessions and will be attractive for professionals, patient/advocacy groups, policy makers and industrial partners. The programme will include evaluation of performance of neonatal screening systems and strategies for improvement.
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

Stem Cells & Regenerative Medicine Congress USA 2015
Date: 2-3 September, 2015
Venue: Washington, United States

The conference will focus on understanding how genomics is changing the field – and highlighting the commercialization and manufacturing stories that have helped spur the recent success.
For further information

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.
For further information


Media, Press & Publications
Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases
This book presents a counter intuitive albeit accurate analysis that studying rare diseases have achieved much of what we now know about common diseases. It proposes that future advances in the prevention, diagnosis, and treatment of common diseases will come as a consequence of our accelerating progress in the field of rare diseases.
Buy the book on AMAZON

International Journal of Technology Assessment in Health Care: issue on ethics and reimbursement
The current issue of the International Journal of Technology Assessment in Health Care focuses on the ethical issues that are floated when dealing with reimbursement of drugs and biologics. The journal has published various articles that address this issue including how ethical arguments can be introduced and integrated in Health Technology Assessment and frameworks that will identify ethical aspects of healthcare technology. Also discussed are the colloquial evidence at NICE, the quality of life measures and vulnerable aspects of HTA. The issue contains appraisal of HTA of medical devices in non-European Union countries as well as evaluation of patient involvement.
Access the issue


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
Contact Us
Editorial Board: Valentina Bottarelli, Victoria Hedley, Yann LeCam, Stephen Lynn, Charlotte Rodwell, Domenica Taruscio, Ariane Weinmann Valentina Bottarelli, Victoria Hedley, Yann LeCam, 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), 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), Dorra H'mida (Tunisia), Ugur Ozbek (Turkey), Dian Donnai (UK)
Orphanet - All rights reserved
Disclaimer : This presentation is part of the project / joint action N° 677024 / RD-ACTION' which has received funding from the European Union's Health Programme (2014-2020).

Photo credit : Serimedis http://www.serimedis.inserm.fr/ (unless otherwise stated)