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A successful RD-action annual meeting: considerable progress made inspiring future work

Launched in June 2015, RD-Action, the joint action of the Member States of the European Union for rare diseases, brings together 64 partners in 40 countries with the aim of developing and sustaining the Orphanet base and implementing priorities particularly in order to improve the codification of rare diseases. In particular, the aim of this action is to foster dialogue between Member States and Europe and to bring the production of data into synergy with the needs for the implementation of European policy priorities.

RD-Action partners met on 26 and 27 October in Paris to review the achievements of the first year of the action and discuss the year ahead. Achievements around four themes were addressed: Increase visibility of rare diseases; Implementing policies for rare diseases and promoting dialogue at national and European level; Interconnect policies for rare diseases in member states; Optimize collaborations and resources.

The R & D Coordinator, Ana Rath (Director of Orphanet, INSERM), opened the day by reviewing achievements and activities aimed at improving the visibility of rare diseases and adapting Orphanet to the new Scientific and political landscape. Evolutions of Orphanet data and procedures have therefore been presented. The importance of the implementation of the ORPHA codes in the European Member States was emphasized (in particular by Rémy Choquet of the BNDMR and by Stefanie Weber of the DIMDI): this is an essential element in the identification of patients, Improving knowledge, particularly epidemiology, and interoperability between health and research, in particular within the framework of the European Reference Networks. The second session of this day highlighted the important steps taken in the implementation of policies for rare diseases in the EU Member States and in maintaining a dialogue both at national and European level. National conferences for rare diseases to be organized with the support of EURORDIS by the national alliances of the different European countries will be the main vehicle for this dialogue. The report on the state of the art of rare diseases is also part of this dialogue, as are the working groups set up to promote the equity of health systems in the field of rare diseases. The action of RD-Action to support the development phase of future European reference networks has played a facilitating role in this construction, and will continue once these networks have been labeled. Finally, it was pointed out that the international OrphaNews newsletter, vector for the dissemination of RD-Action, now counts more than 16,700 subscribers. The dissemination and dialogue role of the European Conference on Rare Diseases and Orphan Products (ECRD 2016) was an important achievement of the first year of work. Finally, possible synergies with other areas and initiatives were outlined, in particular the common objectives of RD-Action and the Joint Action for Rare Cancers (JARC) for the improvement of epidemiological surveillance and research . Scientific collaborations are also under way, for example with RD-Connect and HIPBI-RD.

The commitment of RD-Action partners to the achievement of their objectives was demonstrated, as was the enthusiasm and energy of the partners to continue the work. The advent of the European Reference Networks will give additional impetus to actions which will provide an interesting opportunity for development.

National & International Policy Developments
Other European news
Challenges raised by cross-border testing of rare diseases in the European union
Cross-border testing has been an area of much work in the European Union in recent years. The right to choose where to receive medical treatment across the EU, and to be reimbursed for it is now available to all European citizens. This is of great importance to rare disease patients as expertise can be scarce and scattered. An article published in European Journal of Human Genetics discusses the experiences of the genetic testing of rare diseases in the Member States of the EU. Data collected using web-based questionnaires and phone interviews collected using the Orphanet database showed that there were several challenges faced by patients while getting genetic testing in another country. The variability in documentation requirements was one of the biggest problems that is faced. Additionally, the authors also noted that there were some countries, such as the eastern European countries, the quality and access to genetic testing nationally and abroad was limited. Financial aspects of testing such as variable test pricing and reimbursement as well as collection of payments were found to be problematic. According to the authors findings from this study will help “facilitate and organize cross-border testing, common practices need to be created at the level of the EU, and follow-up studies are needed to monitor their effects.”
Read the PubMed abstract

European Member States collaborate to negotiate prices for orphan drugs
In the World Health Organization Bulletin, an article addresses the future of funding access to orphan drugs. According to the article, European Medicines Agency recommended 89 different orphan medicinal products for marketing authorisation in Europe, by the end of 2015. However, many of these drugs are heavily priced to compensate for the research cost and lower market size.

According to the authors, while pricing and reimbursement is negotiated individually with pharmaceutical companies in each Member State in Europe, this is changing. Two European countries – Belgium and the Netherlands – have teamed up to negotiate the pricing of orphan drugs with pharmaceutical companies. A pilot project was scheduled to begin in 2016. Since the agreement was signed, several pharmaceutical companies have declared their willingness to cooperate in the pilot project. In September 2015, the Grand Duchy of Luxemburg joined the Belgium–Netherlands project and the health ministers of other EU countries have demonstrated their interest in the project.

The authors note that “this collaboration has a potential triple benefit: (i) for health system sustainability; (ii) for pharmaceutical companies; and (iii) for patients having a rare disease.”
Read the WHO Bulletin

ELIXIR survey to address infrastructure needs of the rare disease community
Work package 8 in the Elixir Excelerate program addresses the infrastructure needs of the rare disease community. The aim is to help create and maintain sustainable ELIXIR resources in the long term. As part of this effort we need to determine the current usage and needs of the community. We kindly ask you to complete this survey. Deadline to complete the survey is 25 November, 2016

Your response will help in prioritising the most important bioinformatics tools, what needs to be improved, and will ultimately lead to better ELIXIR services adapted to the requirements of the community. If you are not able to answer these questions yourself, please forward it to an appropriate colleague.

International Recommendations for Undiagnosed patients
EURORDIS (Rare Diseases Europe), together with SWAN UK (the support group run by Genetic Alliance UK), the Wilhelm Foundation, Rare Voices Australia (RVA), the Canadian Organization for Rare Disorders (CORD), the Advocacy Service for Rare and Intractable Diseases' stakeholders in Japan (ASrid) and the National Organization for Rare Disorders (NORD) jointly submit a list of recommendations to address the specific needs of patients without a diagnosis urging all stakeholders to recognise undiagnosed patients as a specific population within the rare disease community.

Undiagnosed rare disease patients require the availability of a complete health and social care pathway in advance of receiving a diagnosis. Such care should promote their chances of receiving an accurate diagnosis in as efficient and timely way as possible, while ensuring that, until a diagnosis is made, they nevertheless receive the best possible health and social care. These recommendations also highlight the importance of promoting ethical and responsible international data sharing to help inform a clinical diagnosis, accelerate research into novel conditions and provide insights into disease mechanisms. Furthermore, knowledge and information sharing among all stakeholders should be optimally coordinated and fostered so that patients can access appropriate resources in a timely and efficient manner.
For further information

Other International News
Fast-track approval of medicines in Australia
Pharmaceutical companies can now apply for fast-track approval of medicines in Australia, which is especially useful for orphan medications. On Sept 15, 2016, the Australian Government released recommendations that included three pathways to speed market access to breakthrough medicines in Australia. The Therapeutic Goods Administration (TGA) of Australia will collaborate with international medicines regulators, such as the FDA and the EMA to make it easier easier for product sponsors to submit existing assessments. Subsequently, the TGA will introduce a fast-track assessment pathway of new medicines in defined circumstances.

Although regulators will have to rely on less clinical data, this will countered by enhanced post-market monitoring to promptly detect emerging problems and have them addressed.
Read more

FDA awards 21 grants to stimulate product development for rare diseases
The U.S. Food and Drug Administration has awarded 21 new clinical trial research grants totaling more than $23 million over the next four years to boost the development of drugs and products for patients with rare diseases. These new grants were awarded to principal investigators from academia and industry with research spanning domestic and international clinical sites.

A total of 68 grant applications were received for this fiscal year, with a funding rate of 31 percent. The grant recipients for fiscal year 2016 included for a variety of drugs and biologics for rare diseases as well as 1 medical device.
Read the FDA press release

Rare diseases in China
With arguably the largest incidence of rare disease, authors of an article published in the Intractable Rare Disease Research discuss the magnitude of the challenges the Chinese are faced with to manage their burden of rare diseases. According to the authors, despite the magnitude there is much promise due the social support available to patients and the push towards educating government bodies and clinicians. The authors believe that with the advent of next generation sequencing, especially non-invasive prenatal testing, there is a possibility of reducing the number of individuals with rare genetic diseases over time. The key according to them is to develop cost-effective treatments backed by government subsidies.
Read the PubMed abstract

Burden of rare diseases in Western Australia
A study published in Genetics in Medicine addresses the shortage of epidemiological data on the burden of rare diseases in Western Australia. The authors gathered data from hospitals in order to understand the collective health and economic impacts of rare diseases. According to the authors "the total cost of hospital discharges for the study cohort represented 10.5% of 2010 state inpatient hospital costs." They believe that this study provides "evidence of a marked disparity between the proportion of the population with rare diseases and their combined health-system costs." The authors hope that the "novel methodology used will inform future rare-disease studies, and the evidence will guide government strategies for managing the service needs of people living with rare diseases."
Read the PubMed abstract

Guidance Documents and Recommendations
Anti-neutrophil cytoplasmic antibody-associated vasculitis: recommendations for the management
Consult the Pubmed abstract
To read more about "Anti-neutrophil cytoplasmic antibody-associated vasculitis"

Ann Rheum Dis. ; 75(9):1583-94 ; September 2016
Waldenström macroglobulinemia: recommendations for the treatment
Consult the Pubmed abstract
To read more about "Waldenström macroglobulinemia"

Blood ; 128(10):1321-8 ; September 2016

Ethical, Legal & Social Issues
The Hidden Cost of rare diseases: a feasibility study by Genetic Alliance UK
Genetic Alliance UK is a national charity based in the United Kingdom that works tirelessly to improve the lives of patients and families affected by genetic conditions, many of which are rare diseases. They have published The Hidden Costs Feasibility Study for patients suffering from rare diseases. According to Genetic Alliance UK, the entirety of the economic and psychosocial toll that managing a rare disease takes, has not been investigated thoroughly. They study supports the development of future research in this area in a number of ways. Findings of this report revealed that:
“ 1. Receiving coordinated care is important for rare disease patients, yet remains a challenge
2. The full costs and benefits associated with different models of care for rare disease patients are unknown
3. Patients and families face significant (‘hidden’) costs (both financial and psychosocial) associated with the way that their care is managed
There are significant limitations associated with existing data sets for rare diseases”

According to Genetic Alliance, the information provided in the report would be “valuable evidence for decision makers and commissioners as they plan service developments and support best practice.”

Send your nominations for NORD’s 2017 Rare Impact Awards
National Organization of Rare Diseases (NORD) is one of the largest American nonprofit organization helping rare disease patients. They are now accepting nominations for its annual Rare Impact Awards. Nominees for the 2017 Rare Impact Awards can include people or organisations and are not restricted by age or category. The awardees will be determined by a nominations committee comprised of NORD’s Scientific and Medical Advisory Committee, Board of Directors, and advocates.

Submissions are now open online at www.rareimpact.org/awards, which will close on Friday, January 13, 2017. The Rare Impact Awards ceremony will be held on May 18, 2017 in Washington D.C. United States.

A case for the Certified Duchenne Care Center Program
An article published in Neuromuscular Disorders describes the development of Certified Duchenne Care Centers (CDCCs) in the United States. According to the authors, implementation of the CDC care for Duchenne Muscular Dystrophy (DMD) guidelines for its care varied across the country which led to "different clinical outcomes, confounded interpretation of clinical trial results and delayed drug development for Duchenne." Thus the Parent Project Muscular Dystrophy felt the need to launch Transforming Duchenne Care Initiative, which helped the development of the Certified Duchenne Care Center Program. According to the authors, this programme ensures uniform standard of care is provided at CDCCs across the United States. They believe that the "goals are to increase quality and improve access to care through standardization and to strengthen the ability of natural history studies and industry-sponsored trials to deliver reliable results."
Read the PubMed abstract


New Syndromes

Intellectual disability syndrome with persistence of foetal haemoglobin caused by BCL11A haploinsufficiency in 11 individuals
The authors reported an intellectual disability syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A in 11 individuals. Patients shared clinical features, including persistence of foetal haemoglobin.
Consult the Pubmed abstract

Am J Hum Genet. ; 99(2):253-74 ; August 2016
Growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and infantile hepatopathy due to biallelic IARS mutations in three individuals
Exome sequencing in three unrelated individuals with severe prenatal-onset growth retardation, intellectual disability, and muscular hypotonia revealed biallelic mutations in IARS. Two of the individuals had infantile hepatopathy with fibrosis and steatosis, leading in one to liver failure in the course of infections. Zinc deficiency was present in all affected individuals and supplementation with zinc showed a beneficial effect on growth in one.
Consult the Pubmed abstract

Am J Hum Genet. ; 99(2):414-22 ; August 2016
Early-onset epileptic encephalopathy with progressive cerebral, cerebellar, and optic nerve atrophy linked to biallelic CACNA1A mutations in two siblings
The authors described two patients, sister and brother, with compound heterozygous mutations in CACNA1A. Both patients were normal at birth, but developed daily recurrent seizures in early infancy with concomitant extreme muscular hypotonia, hypokinesia, and global developmental delay. The brain MRI images showed progressive cerebral, cerebellar, and optic nerve atrophy. At the age of 5, both patients were blind and bedridden with a profound developmental delay. The elder sister died at that age. Their parents and two siblings were heterozygotes for one of those pathogenic mutations and expressed a milder phenotype. Both of them had intellectual disability and in addition the mother had adult onset cerebellar ataxia with a slowly progressive cerebellar atrophy.
Consult the Pubmed abstract

Am J Med Genet A. ; 170(8):2173-6 ; August 2016
Novel craniofacial syndrome due to ARCN1 mutations The authors reported a clinically recognisable craniofacial
The authors reported a clinically recognisable craniofacial disorder due to loss-of-function heterozygous mutations in ARCN1. This disorder was characterised by facial dysmorphisms, severe micrognathia, rhizomelic shortening, microcephalic dwarfism, and mild developmental delay.
Consult the Pubmed abstract

Am J Hum Genet. ; 99(2):451-9 ; April 2016
Cone-rod dystrophy and hearing loss associated with primary-cilia defects caused by mutations in CEP78
In a first article, the authors identified biallelic mutations in CEP78 in three subjects from two families. The three individuals presented with cone-rod degeneration and hearing loss or hearing deficit.
In a second article, six individuals presented with an uncommon combination of autosomal recessive progressive cone-rod degeneration accompanied by sensorineural hearing loss. Homozygosity mapping followed by whole-exome sequencing and founder mutation screening revealed two truncating rare variants in CEP78.
Consult the Pubmed abstracts

Am J Hum Genet. ; 99(3):770-6; 777-84 ; September 2016
Paediatric-onset neurological disease associated with biallelic mutations of VAC14 in two unrelated children
The authors described inherited variants of VAC14 in two unrelated children with sudden onset of a progressive neurological disorder and regression of developmental milestones. Both children developed impaired movement with dystonia, became non-ambulatory and non-verbal, and exhibited striatal abnormalities on MRI. A diagnosis of Leigh syndrome was rejected due to normal lactate profiles. Exome sequencing identified biallelic variants of VAC14 that were inherited from unaffected heterozygous parents in both families.
Consult the Pubmed abstract

Am J Hum Genet. ; 99(1):188-94 ; July 2016
Cancer-prone bone marrow failure syndrome linked to DNAJC21 mutations
Through exome sequencing, the authors identified a subgroup of individuals defined by germline biallelic mutations in DNAJC21. They presented with global bone marrow failure, and one individual developed a haematological cancer (acute myeloid leukaemia) in childhood.
Consult the Pubmed abstract

Am J Hum Genet. ; 99(1):115-24 ; July 2016
Novel hereditary spastic paraplegia and ataxia caused by a recurrent mutation in KCNA2
The authors identified a recurrent mutation in KCNA2 in two unrelated families with hereditary spastic paraplegia, intellectual disability, and ataxia. Follow-up analysis of > 2,000 patients with various neurological phenotypes identified a de novo mutation in KCNA2 in a proband with ataxia and intellectual disability.
Consult the Pubmed abstract

Ann Neurol. ; 80(4) ; October 2016
Infantile onset phenotype including severe myoclonus with evidence of mitochondrial dysfunction associated with KIF5A mutations
The authors reported on two patients with de novo stop-loss frameshift variants in KIF5A resulting in a novel phenotype. This syndrome included severe infantile onset myoclonus, hypotonia, optic nerve abnormalities, dysphagia, apnea, and early developmental arrest.
Consult the Pubmed abstract

Ann Neurol. ; 80(4):633-7 ; October 2016

New Genes

Early infantile epileptic encephalopathy caused by SLC1A2 and CACNA1A de novo mutations
Consult the Pubmed abstract
To read more about "Early infantile epileptic encephalopathy"

Am J Med Genet A. ; 170(9):2237-47 ; September 2016
Primary microcephaly associated with biallelic variants in CIT
Consult the Pubmed abstracts
To read more about "Autosomal recessive primary microcephaly"

Am J Hum Genet. ; 99(2):501-10; 511-20 ; August 2016
Primary ciliary dyskinesia due to TTC25 deficiency
Consult the Pubmed abstract
To read more about "Primary ciliary dyskinesia"

Am J Hum Genet. ; 99(2):460-9 ; August 2016
Pontocerebellar hypoplasia and progressive microcephaly linked to autosomal recessive mutations in TSEN15
Consult the Pubmed abstract
To read more about "Pontocerebellar hypoplasia type 2"

Am J Hum Genet. ; 99(1):228-35 ; July 2016
X-linked sideroblastic anaemia caused by a recurring mutation in NDUFB11 in five males
Consult the Pubmed abstract
To read more about "X-linked sideroblastic anemia"

Blood ; 128(15):1913-1917 ; October 2016
Autosomal dominant tubulo-interstitial and glomerulocystic kidney disease with anaemia linked to heterozygous loss-of-function SEC61A1 mutations
Consult the Pubmed abstract
Am J Hum Genet. ; 99(1):174-87 ; July 2016
Oculopharyngeal muscular dystrophy caused by a recessive loss-of-function mutation of the NRL gene in two patients
Consult the Pubmed abstract
To read more about "Oculopharyngeal muscular dystrophy"

Invest Ophthalmol Vis Sci. ; 57(13):5361-5371 ; October 2016
Paediatric-type nodal follicular lymphoma linked to MAP2K1, MAPK1, RRAS, TNFRSF14 and KMT2D mutations
Consult the Pubmed abstracts
To read more about "Follicular lymphoma"

Blood ; 128(8):1093-100; 1101-11 ; August 2016
Nodal marginal zone B-cell lymphoma due to mutations in PTPRD
Consult the Pubmed abstract
To read more about "Nodal marginal zone B-cell lymphoma"

Blood ; 128(10):1362-73 ; September 2016
Systemic sclerosis: IRF4 and TYK2 as susceptibility genes
Consult the Pubmed abstracts
To read more about "Systemic sclerosis"

Arthritis Rheumatol. ; 68(9):2338-44 ; September 2016
Ann Rheum Dis. ; 75(8):1521-6 ; August 2016
Juvenile dermatomyositis: C4A as a susceptibility gene
Consult the Pubmed abstract
To read more about "Juvenile dermatomyositis"

Ann Rheum Dis. ; 75(9):1599-606 ; September 2016

Research in Action

Clinical Research
Severe combined immunodeficiency due to adenosine deaminase deficiency: 100% of survival with gene therapy
Consult the Pubmed abstract
To read more about "Severe combined immunodeficiency due to adenosine deaminase deficiency"

Blood ; 128(1):45-54 ; July 2016
Thalassemia major: amlodipine combined with chelation therapy reduces cardiac iron more effectively that chelation therapy alone
Consult the Pubmed abstract
To read more about "Beta-thalassemia major"

Blood ; 128(12):1555-61 ; September 2016
Chronic graft versus host disease: low-dose interleukin-2 therapy is efficacious and well-tolerated
Consult the Pubmed abstract
To read more about "Chronic graft versus host disease"

Blood ; 128(1):130-7 ; July 2016
Polymyalgia rheumatica: tocilizumab may be an effective, safe, and well-tolerated treatment for newly diagnosed patients
Consult the Pubmed abstracts
To read more about "Polymyalgia rheumatica"

Arthritis & Rheumatology ; 68(10):2550-4 ; October 2016
Annals of the Rheumatic Diseases ; 75(8):1506-10 ; August 2016
Acute lymphoblastic leukaemia: dasatinib and low-intensity chemotherapy is well-tolerated and gives long-term survival in 36% of elderly patients
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Acute lymphoblastic leukemia"

Blood ; 128(6):774-82 ; August 2016
Panobinostat induces responses in 28% of patients with relapsed and refractory diffuse large B-cell lymphoma
Consult the Pubmed abstract
To read more about "Diffuse large B-cell lymphoma"

Blood ; 128(2):185-94 ; July 2016
Hodgkin lymphoma: remission for more than five years using brentuximab vedotin
Consult the Pubmed abstract
To read more about "Hodgkin lymphoma"

Blood ; 128(12):1562-6 ; September 2016
Multiple myeloma: pomalidomide plus low-dose dexamethasone is efficient and well-tolerated
Consult the Pubmed abstract
Consult this Austrian study on Orphanet
Consult this Spanish study on Orphanet

To read more about "Multiple myeloma"

Blood ; 128(4):497-503 ; July 2016
Immune thrombocytopenic purpura: comparable neonatal outcomes for mothers who receive intravenous immunoglobulin or corticosteroids
Consult the Pubmed abstract
To read more about "Immune thrombocytopenic purpura"

Blood ; 128(10):1329-35 ; September 2016
Eosinophilic granulomatosis with polyangiitis: mitigated results with omalizumab
Consult the Pubmed abstract
To read more about "Eosinophilic granulomatosis with polyangiitis"

Arthritis Rheumatol. ; 68(9):2274-82 ; September 2016
Systemic-onset juvenile idiopathic arthritis: tocilizumab is well-tolerated, with acceptable effectiveness
Consult the Pubmed abstract
To read more about "Systemic-onset juvenile idiopathic arthritis"

Ann Rheum Dis. ; 75(9):1654-60 ; September 2016
Acute myeloid leukaemia: systematic literature review and recommendations for maintenance therapy
Consult the Pubmed abstract
To read more about "Acute myeloid leukemia"

Blood ; 128(6):763-73 ; August 2016
Chronic myeloid leukaemia: increased risk for arterial and venous vascular events in patients treated with tyrosine kinase
Consult the Pubmed abstract
To read more about "Chronic myeloid leukemia"

Ann Intern Med. ; 165(3):161-6 ; August 2016
IgG4-related disease: retrospective analysis of 166 patients
Consult the Pubmed abstract
To read more about "IgG4-related disease"

Arthritis Rheumatol. ; 68(9):2290-9 ; September 2016
Therapeutic Approaches

Hutchinson-Gilford progeria syndrome: seven compounds that normalise the osteogenic differentiation process identified through high throughput screening in a cellular model
Consult the Pubmed abstract
To read more about "Hutchinson-Gilford progeria syndrome"

Sci Rep. ; 6:34798 ; October 2016
Down syndrome: infantile spasms rescued using the GIRK antagonist tertiapin-Q in mice
Consult the Pubmed abstract
To read more about "Down syndrome"

Ann Neurol. ; 80(4):511-21 ; October 2016
Hemophagocytic syndrome: ruxolitinib treatment leads to recovery in murine models
Consult the Pubmed abstract
To read more about "Hemophagocytic syndrome"

Blood ; 128(1):60-71 ; July 2016
Multiple myeloma: novel zebrafish model
Consult the Pubmed abstract
To read more about "Multiple myeloma"

Blood ; 128(2):249-52 ; July 2016
Diagnostic Approaches

Comparing clinical features in 48 children with microscopic polyangiitis to 183 children with polyangiitis
Consult the Pubmed abstract
To read more about "Microscopic polyangiitis"
To read more about "Granulomatosis with polyangiitis"

Arthritis Rheumatol. ; 68(10):2514-26 ; October 2016
Small vessel disease: peak width of skeletonised mean diffusivity is a new, fully automated, and robust imaging marker
Consult the Pubmed abstract
To read more about "Familial vascular leukoencephalopathy"

Ann Neurol. ; 80(4):581-92 ; October 2016
Systemic auto-inflammatory diseases: suitable molecular diagnosis with a next-generation sequencing-based protocol designed to simultaneous screening of 10 genes
Consult the Pubmed abstract
Ann Rheum Dis. ; 75(8):1550-7 ; August 2016
Congenital muscular dystrophy: next generation sequencing as a first-line tool for genetic evaluation of patients with a clinical phenotype suggestive of the disease
Consult the Pubmed abstract
To read more about "Congenital muscular dystrophy"

Ann Neurol. ; 80(1):101-11 ; July 2016
Sporadic Creutzfeldt-Jakob disease: cerebrospinal fluid real-time quaking-induced conversion is a robust and reliable test
Consult the Pubmed abstract
To read more about "Sporadic Creutzfeldt-Jakob disease"

Ann Neurol. ; 80(1):160-5 ; July 2016
Myeloid malignancies: development and validation of Karyogene, a comprehensive genomic diagnostic tool
Consult the Pubmed abstract
Blood ; 128(1):e1-9 ; July 2016

Patient Management and Therapy
Acromegaly: two reviews on therapies
Consult the Pubmed abstracts
To read more about "Acromegaly"

Growth Horm IGF Res. ; [Epub ahead of print] ; October 2016
Expert Opin Pharmacother. ; 17(12):1631-42 ; August 2016
Scleroderma: review on haematopoietic stem cell transplantation
Consult the Pubmed abstract
To read more about "Scleroderma"

Arthritis Rheumatol. ; 68(10):2361-71 ; October 2016
Haematologic malignancies: five reviews on cell therapy
Consult the Pubmed abstracts
Blood ; 127(26):3312-20, 3321-30, 3331-40, 3341-9, 3350-9 ; June 2016
Haematologic malignancies: review on gene therapy
Consult the Pubmed abstract
Blood ; 127(26):3305-11 ; June 2016
Chronic myeloid leukaemia: review on treatment and remission
Consult the Pubmed abstract
To read more about "Chronic myeloid leukemia"

July 2016 ; 128(1):17-23 ; Blood
Lymphoma: review on idelalisib for the management
Consult the Pubmed abstract
To read more about "Lymphoma"

Blood ; 128(3):331-6 ; July 2016
Acute flaccid myelitis: review of US cases
Consult the Pubmed abstract
To read more about "Spinal cord injury"

Ann Neurol. ; 80(3):326-38 ; September 2016
Multiple myeloma: review on immunotherapy
Consult the Pubmed abstract
To read more about "Multiple myeloma"

Blood ; 128(13):1679-87 ; September 2016
AL amyloidosis: review on diagnosis and management
Consult the Pubmed abstract
To read more about "AL amyloidosis"

Blood ; 128(2):159-68 ; July 2016
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency and combined immunodeficiency due to LRBA deficiency: a review
Consult the Pubmed abstract
To read more about "Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency"
To read more about "Combined immunodeficiency due to LRBA deficiency"

Blood ; 128(8):1037-42 ; August 2016
Acromegalic osteopathy: a review
Consult the Pubmed abstract
To read more about "Acromegaly"

Pituitary ; [Epub ahead of print] ; October 2016
Interstitial lung disease specific to infancy: a review
Consult the Pubmed abstract
To read more about "Interstitial lung disease specific to infancy"

Radiol Clin North Am. ; 54(6):1065-1076 ; November, 2016
Zika virus disease: two reviews
Consult the Pubmed abstracts
To read more about "Zika virus disease"

Ann Intern Med. ; 165(3):175-83 ; August 2016
Ann Neurol. ; 80(4):479-89 ; October 2016
Neuroblastoma: a review
Consult the Pubmed abstract
To read more about "Neuroblastoma"

Ann Neurol. ; 80(1):13-23 ; July 2016
Two new and six updated GeneReviews published
GeneReviews are expert-authored, peer-reviewed disease descriptions ("chapters") presented in a standardized format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions. Two new GeneReviews have been published for:
DEPDC5-related epilepsy
GRIN2A-related speech disorders and epilepsy

Six updated GeneReviews have been published for:
Propionic acidemia
RASA1-related disorders
Perry syndrome
Werner syndrome
Xeroderma pigmentosum


Orphan Drugs
Multi-criteria decision analysis for assessment and appraisal of orphan drugs in Bulgaria
An article published in Frontiers in Public Health created an multi-criteria decision analysis (MCDA) value measurement model to assess and appraise orphan drugs by utlising data arising from stakeholders in Bulgaria. According to the authors, "this study proved that strength of evidence may be a key criterion in orphan drug assessment and appraisal." The authors believe that "improved knowledge on MCDA feasibility and integration to HTA is of paramount importance, as progress in medicine and innovative health technologies should correspond to patient, health-care system, and societal values."
Read the PubMed abstract

New medicine for rare, chronic liver disease
The European Medicines Agency has recommended granting a conditional marketing authorisation to Ocaliva (obeticholic acid) for the treatment of patients with primary biliary cholangitis. Ocaliva is to be used in combination with another medicine, ursodeoxycholic acid (UDCA), in patients who have not responded adequately to UDCA, or on its own in adults who are unable to tolerate treatment with UDCA.

Primary biliary cholangitis is a rare and life threatening disease that causes the gradual destruction of the small bile ducts in the liver. As the disease progresses, it leads to liver cirrhosis and liver failure. Obeticholic acid is a semisynthetic bile acid that works by activating the farnesoid X receptor (FXR), which controls the production of bile thus reducing the exposure of the liver to toxic levels of bile acids.
For further information

Political and Scientific News
A Bayesian adaptive design for clinical trials in rare diseases
It has long been known that a traditional fixed randomised design clinical trial may not be a plausible goal for testing orphan drugs. An alternative goal is to treat the patients within the trial as effectively as possible. The authors of an article published in Computational Statistics & Data Analysis proposes the framework of finite-horizon Markov decision processes and dynamic programming (DP), a novel randomised response-adaptive design. Utilising this method enables the maximisation of the total number of patient successes in the trial and penalises if a minimum number of patients are not recruited to each treatment arm. According to the authors “simulation results for the proposed design show that: (i) the percentage of patients allocated to the superior arm is much higher than in the traditional fixed randomised design; (ii) relative to the optimal DP design, the power is largely improved upon and (iii) it exhibits only a very small bias and mean squared error of the treatment effect estimator.” Furthermore, the authors note that this design is fully randomised which is an advantage from a practical point of view because it protects the trial against various sources of bias.
Read the Open Access article

Disease-specific clinical trials networks: the example of cystic fibrosis
An article published in European Journal of Pediatrics describes the steps of the development and the structure of a disease-specific clinical trials network for cystic fibrosis in Europe. They provide the example of the European Cystic Fibrosis Society Clinical Trials Network which has facilitated "the development of new treatments for a rare disease and could be a prototype for other diseases."
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

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

Palliative Care Needs of Individuals with Rare Advanced Diseases and Their Family Caregivers (R01 and R21)
This funding opportunity announcement (FOA) seeks to expand knowledge and increase the evidence base for palliative care (PC) in advanced rare diseases, including rare cancers, and to improve physical and psychosocial well-being and quality of life among seriously ill individuals and their family caregivers. This funding opportunity announcement (FOA) seeks to expand knowledge and increase the evidence base for palliative care (PC) in advanced rare diseases, including rare cancers, and to improve physical and psychosocial well-being and quality of life among seriously ill individuals and their family caregivers. The deadline for receipt of applications is the 8 January 2017.
For more information on the R01 grant
For more information on the R21 grant

E-Rare-3 Call for proposals 2017: Transnational Research
Projects for Innovative Therapeutic Approaches for Rare Diseases The aim of the call is to enable scientists in different countries to build an effective collaboration on a common interdisciplinary research project based on complementarities and sharing of expertise, with a clear translational research approach. Projects shall involve a group of rare diseases or a single rare disease following the European definition i.e. a disease affecting not more than five in 10.000 persons in the European Community, EC associated states and Canada.
The deadline for receipt of applications is the 8 January 2017.
For more information


Partnersearch, Job Opportunities
The Sisley-D'Ornano Foundation and the Jerome Lejeune Foundation join their efforts to fund for academic research dedicated to bettering our understanding on cross neurological pathologies, epidemiological analysis, risks and threats and physiopathology and potential therapies between Down syndrome and other pathologies developed by population such as and not exclusively limited to Alzheimer disease, dementia and autism. This process is built in accordance to the European Chart referenced on the following link The Sisley-D'Ornano and Jerome Lejeune Foundations are offering one Post-Doctoral Fellowship to outstanding researcher. The work will have to begin in 2017. Please find hereafter the link for more details concerning this application: 2016 Postdoctoral application The candidates should be presented by institutions/Research Units and hosted by them. One candidate will be selected early 2017. Deadline for submission: Dec 15, 2016. Another postdoctoral application process will be put in place end of 2017 to select another candidate.

Courses & Educational Initiatives
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 radiz Symposium 2016 on rare diseases
The radiz Symposium 2016 on rare diseases will take place in the main lecture hall at the Kinderspital Zürich, on the 1st of December 2016, starting at 2 pm and ending at 6 pm with a networking apéro. Our scientists from the Children's Hospital Zurich, the University of Zurich, and the University Hospital Zurich will give you an insight into the findings of their research projects on rare diseases. The lectures will be held mostly in German. Further details about the event can be found at here
The radiz Symposium is open to the public, free of charge, and no registration is needed.

ExPRESS 2017 Expert Patient and Researcher EURORDIS Summer School
Date: June 5-9, 2017

Venue: Barcelona, Spain

The programme allows patients and researchers to sharpen their advocacy skills and gain an understanding of the regulatory process of orphan medicinal products so that they are able to advocate at a European level. The programme has online and face-to-face components. The face-to-face portion trains 40 expert patients annually as part of an intensive 4.5 day course held in Barcelona, Spain.
For further information


What's on Where?

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

Patients as Partners EU
Date: 6-7 February 2017
Venue: London, United Kingdom

Patients as Partners EU is co-produced with patients, industry, academia, government and nonprofit organizations to establish a well-rounded program that addresses the needs of all stakeholders seeking to implement and advance patient involvement across the entire clinical development continuum.
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

5th Annual Paediatric Oncology Conference
Date: 2-3 March, 2017
Venue: Brussels, Belguim

The conference is part of a unique multi-stakeholder joint initiative, the ACCELERATE multi-stakeholder Platform. Co-organised by CDDF, ITCC and SIOPE, this platform provides a transparent forum enabling patients and parents’ organisations, academic paediatric oncologists and haematologists, pharmaceutical companies and EU regulatory network representatives to collaborate and jointly address specific obstacles to a faster and more effective treatments for children and adolescents with cancer, including the needed changes to the Paediatric Medicines Regulation.
For further information

15th WFH International Musculoskeletal Congress
Date: 5-7 May, 2017
Venue: Seoul, South Korea

The Congress program will feature presentations, posters, and exhibit displays with a focus on musculoskeletal approaches to hemophilia. Key developments in the field will be addressed, making the event relevant to orthopedists and physical therapists around the world.
For further information

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

For further information


Commercial events

Pharma Pricing & Market Access Congress
Date: 22-23 February, 2017
Venue: London, United Kingdom

Discuss pricing, patient centricity and global market access all in one place. With collaboration high on the agenda, World Pharma Pricing and Market Access gives you excellent opportunities to hear from payers, pharma, patient led organisations and providers. Attend Europe’s largest, most respected market access and pricing conference to benchmark y0strategic decision making. - See more at: http://www.healthnetworkcommunications.com/conference/pharma-pricing/index.stm#sthash.OxQSl6E4.dpuf
For further information

World Orphan Drugs Congress Asia
Date: 3-4 June, 2017
Venue: Singapore

Bringing together specialised biotechs/pharmas, government, payers, investors & patient groups in one platform, this event offers a unique opportunity to increase brand visibility amongst the rare disease industry in Asia.
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
Contact Us
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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