[{"command":"openDialog","selector":"#drupal-modal","settings":null,"data":"\u003Cdiv id=\u0022republish_modal_form\u0022\u003E\u003Cform class=\u0022modal-form-example-modal-form ecl-form\u0022 data-drupal-selector=\u0022modal-form-example-modal-form\u0022 action=\u0022\/en\/article\/modal\/9254\u0022 method=\u0022post\u0022 id=\u0022modal-form-example-modal-form\u0022 accept-charset=\u0022UTF-8\u0022\u003E\u003Cp\u003EHorizon articles can be republished for free under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence.\u003C\/p\u003E\n \u003Cp\u003EYou must give appropriate credit. We ask you to do this by:\u003Cbr \/\u003E\n 1) Using the original journalist\u0027s byline\u003Cbr \/\u003E\n 2) Linking back to our original story\u003Cbr \/\u003E\n 3) Using the following text in the footer: This article was originally published in \u003Ca href=\u0027#\u0027\u003EHorizon, the EU Research and Innovation magazine\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003ESee our full republication guidelines \u003Ca href=\u0027\/horizon-magazine\/republish-our-stories\u0027\u003Ehere\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003EHTML for this article, including the attribution and page view counter, is below:\u003C\/p\u003E\u003Cdiv class=\u0022js-form-item form-item js-form-type-textarea form-item-body-content js-form-item-body-content ecl-form-group ecl-form-group--text-area form-no-label ecl-u-mv-m\u0022\u003E\n \n\u003Cdiv\u003E\n \u003Ctextarea data-drupal-selector=\u0022edit-body-content\u0022 aria-describedby=\u0022edit-body-content--description\u0022 id=\u0022edit-body-content\u0022 name=\u0022body_content\u0022 rows=\u00225\u0022 cols=\u002260\u0022 class=\u0022form-textarea ecl-text-area\u0022\u003E\u003Ch2\u003EThe long journey to a rare disease diagnosis \u003C\/h2\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\n\n\u003Cp\u003E\u2018With rare diseases, the big problem today is in diagnosis as this is required for effective treatment,\u2019 said Dr Holm Grae\u00dfner, managing director of the rare disease centre in T\u00fcbingen, Germany. \u2018On average it takes five years for a patient to get a diagnosis \u2013 if a diagnosis is made at all.\u2019\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EWhen there\u2019s a delayed diagnosis, or no diagnosis, the patient has no entry gate to the healthcare system. They\u2019re moved from practitioner to practitioner and from false diagnosis to false diagnosis.\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EDr Holm Grae\u00dfner, managing director of the rare disease centre in T\u00fcbingen, Germany\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\n\n\u003Cp\u003EHe added: \u2018When there\u2019s a delayed diagnosis, or no diagnosis, the patient has no entry gate to the healthcare system. They\u2019re moved from practitioner to practitioner and from false diagnosis to false diagnosis. It\u2019s very distressing for the patient and very costly for the system.\u2019\u003C\/p\u003E\n\n\u003Cp\u003EIn 2018, rare disease experts from across Europe teamed up to fix this problem - the \u201cdiagnosis\u2019 odyssey\u201d - through an on-going EU-funded project called \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/779257\u0022 target=\u0022_blank\u0022\u003ESolve-RD\u003C\/a\u003E. The project brings together more than 300 clinicians, scientists, and patient representatives from 51 sites across 15 European countries with an objective that is as simple as it is ambitious: to solve the unsolved rare diseases.\u003C\/p\u003E\n\n\u003Cp\u003EThe rareness of these diseases makes them difficult to name and treat when clinics and laboratories operate in isolation. The strength of Solve-RD lies in its ability to pool resources, and therefore amplify the likelihood of diagnosis. Solve-RD builds upon the networking nature of several \u0022European Reference Networks\u0022 (ERNs), a series of virtual networks involving healthcare providers across Europe, where discussions are held on complex rare diseases.\u003C\/p\u003E\n\n\u003Cp\u003EAddressing the problem of doctors and researchers working in national silos, Dr Grae\u00dfner said: \u2018Due to there being so many rare diseases, and due to their rarity (in any given place), there is a scarcity of experts and knowledge, so treatment and care quality are often not appropriate.\u2019\u003C\/p\u003E\n\n\u003Cp\u003EThe Solve-RD researchers are taking two approaches to this massive undertaking. The first is a re-analysis of existing genomic data from 23,000 patients. The second is the application of novel \u201comics\u201d technologies on samples from 6,000 patients. Omics allows scientists to analyse a patient\u2019s metabolome (a list of all the molecules found in their cells) and epigenome (the chemical compounds that instruct genes to turn on or off) \u2013 information that will point to disease-causing genetic variants.\u003C\/p\u003E\n\n\u003Cp\u003E\u2018Because of the collaborative approach we\u2019re taking to the sharing of data and expertise, we\u2019re in a strong position to identify new genes linked to disease, and to deliver a diagnosis to many European patients who remain undiagnosed today,\u2019 said Dr Grae\u00dfner, who has been tasked with coordinating Solve-RD. \u2018We anticipate increasing the diagnostic yield by about 10-20%.\u2019\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003EHow rare is rare?\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003EA rare disease is defined as one that affects fewer than one in 2,000 people. It\u2019s an umbrella term that covers (among other things) rare forms of neurological diseases, metabolic diseases, intellectual disabilities, certain cancers, rheumatologic disorders, complex epilepsies, immune deficiencies and autoinflammatory diseases. Most of these conditions are caused by one or more uncommon gene mutations, so it stands to reason that the key to diagnosis and treatment is to first identify the mutated gene. The next step is to find the protein that is produced from this gene (proteins are required for the structure, function and regulation of the body) and then to find a drug that targets either the gene or the protein, thereby restoring the patient\u2019s health.\u003C\/p\u003E\n\n\u003Cp\u003ETo date, the project\u2019s data re-analysis has solved 444 cases from 8,460 exome and genome datasets from 4,457 families (the genome is a complete set of a person\u2019s genetic information, and exome sequencing reveals all the protein-coding regions of the genome). The researchers anticipate solving over 2,000 additional cases before the project ends in June 2023.\u003C\/p\u003E\n\n\u003Cp\u003EBut the benefits will be felt way beyond this date, as the project plans to leave a legacy in the form of world-class research facilities and the world\u0027s\u0026nbsp;largest genetic dataset\u0026nbsp;for the disease groups covered. This dataset\u0026nbsp;will\u0026nbsp;make it far easier for genetic variations of rare diseases to be identified in the future.\u003C\/p\u003E\n\n\u003Cp\u003EThe creation of\u0026nbsp;the Solve-RD Community Engagement Task Force\u0026nbsp;is another\u0026nbsp;important aspect of the project.\u0026nbsp;This task force is led by\u0026nbsp;\u003Ca href=\u0022https:\/\/www.eurordis.org\/about-eurordis\u0022 target=\u0022_blank\u0022\u003EEURORDIS\u003C\/a\u003E, which represents the voice of the 30 million people affected by rare diseases throughout Europe and reinforces links between 984 rare disease patient organisations across 74\u0026nbsp;countries, to ensure that key resources and knowledge are shared by all.\u003C\/p\u003E\n\n\u003Cp\u003EDr Gulcin Gumus, research and\u0026nbsp;policy project manager for EURORDIS, said: \u0027Even when the project ends, we\u0027ll keep supporting patients. It\u2019s not possible to diagnose everyone, even with the latest technology, so communication on the latest research findings and having a community of support will remain important for people who remain undiagnosed as well as those diagnosed with an ultra-rare disease.\u2019\u003C\/p\u003E\n\n\u003Cp\u003E\u2018Everyone (with a rare disease) needs to talk about their concerns. They want to be involved in their care. They need to be directed to helplines. They want to be notified of updates in diagnosis and treatment.\u2019\u003C\/p\u003E\n\n\u003Cp\u003EAware that effective treatments are in short supply, Dr Grae\u00dfner and his colleagues are also developing a \u201cgenetic therapy approach\u201d that will allow mutation specific drug molecules to be tested in affected individual patients. The results from this work, however, are some way off.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003EInflammatory attacks\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003ESystemic autoinflammatory diseases (SAIDs) are a particularly challenging set of rare conditions for clinicians to treat, as there are no biological markers pointing to an underlying cause.\u003C\/p\u003E\n\n\u003Cp\u003EThough triggered by an impairment in a person\u2019s immune system, SAIDs are not to be confused with autoimmune diseases, which are caused by a faulty antibody response. SAIDs can affect anyone, young or old. Patients present a host of highly non-specific symptoms (such as fever, rash, joint pain, lymph node swelling, and musculoskeletal aching, stiffness and twitching), meaning a diagnosis must be based largely on doctors obtaining a detailed patient history to understand the pattern of symptoms associated with flare-ups.\u003C\/p\u003E\n\n\u003Cp\u003EThis, however, is a blunt instrument, leading to frequent misdiagnoses and ineffective treatments. On average, up to five inadequate or inefficient treatments are prescribed to each patient with a SAID-related condition before a correct diagnosis is made and an appropriate drug is prescribed. But SAID patients are seriously ill soon after disease onset, so a slow diagnosis can have a tremendous impact on their health and quality of life.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EPeople are suffering a lot \u2013 both physically and mentally \u2013 but no-one can tell them what is wrong. And until the patient is correctly diagnosed, he or she can\u2019t benefit from the right treatment.\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Vassilis Soumelis from the Curie Institute in Paris, France\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\n\n\u003Cp\u003ESumming up the problem, SAID researcher Professor Vassilis Soumelis from the Curie Institute in Paris, France, said: \u2018People are suffering a lot \u2013 both physically and mentally \u2013 but no-one can tell them what is wrong. And until the patient is correctly diagnosed, he or she can\u2019t benefit from the right treatment.\u2019\u003C\/p\u003E\n\n\u003Cp\u003EProf. Soumelis is the coordinator\u0026nbsp;of \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/779295\u0022 target=\u0022_blank\u0022\u003EImmunAID\u003C\/a\u003E, a European project that aims to make diagnoses of SAID both faster and more accurate. The five-year project \u2013 which started in 2018 and involves scientists working alongside doctors from 36 clinical centres and patient advocacy groups \u2013 aims to alleviate the spectrum of SAIDs.\u003C\/p\u003E\n\n\u003Cp\u003ESo far, scientists have gathered and analysed huge amounts of biological data from 200 patients living with undiagnosed SAIDs (their target is 700 patients). This data is being analysed for faulty genes and proteins. Experts are also studying the communities of microorganisms living in patients\u2019 intestines, as the gut microbiome is increasingly thought to play a significant role in modulating inflammation.\u003C\/p\u003E\n\n\u003Cp\u003EThe researchers expect important patterns to emerge from their data \u2013 patterns they will use to devise a new, robust system for classifying SAIDs. These classifications will then be reported in a central database that medical teams will have access to, enabling doctors to confidently diagnose and treat patients presenting with SAIDs.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003EThe role of genes\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003EThough many SAIDs remain genetically undiagnosed, it is thought that most autoinflammatory diseases have a strong genetic background, with mutations occurring in single genes. To date, over 30 genes associated with autoinflammatory diseases have been identified.\u003C\/p\u003E\n\n\u003Cp\u003EFamilial Mediterranean Fever is the most common hereditary SAID, and in 1997 it also became the \u003Ca href=\u0022https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0896841120300329?via%3Dihub\u0022 target=\u0022_blank\u0022\u003Efirst SAID gene identified\u003C\/a\u003E as disease-causing. There is no cure for the condition, but when patients are prescribed with the correct anti-inflammatory drugs, attacks can be prevented and symptoms eased.\u003C\/p\u003E\n\n\u003Cp\u003EProf. Soumelis hopes ImmunAID will yield a similar outcome for other SAIDs. \u2018By gathering high-quality data, we have very high expectations of uncovering the underlying mechanism of a condition and putting a diagnosis on it,\u2019 he said.\u003C\/p\u003E\n\n\u003Cp\u003E\u2018Our final goal is to decrease the time from the first suspicion of a disease to a definite diagnosis \u2013 and of course for all patients to receive targeted treatments.\u2019\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cdiv class=\u0022tw-text-center tw-bg-bluelightest tw-p-12 tw-my-12 tw--mx-16\u0022\u003E\n \u003Ch3 class=\u0022tw-font-sans tw-font-bold tw-text-blue tw-uppercase tw-text-lg tw-mb-8\u0022\u003EEU research on rare diseases\u003C\/h3\u003E\n \u003Cspan class=\u0022tw-inline-block tw-w-1\/6 tw-h-1 tw-bg-blue tw-mb-8\u0022\u003E\u003C\/span\u003E\n \u003Cp\u003EThe area of rare diseases has long been a priority area for the EU, and is recognised as a field where EU and international collaboration is an indispensable condition to progress.\u003C\/p\u003E\r\n \u003Cp\u003E The European Commission, through its funding via successive framework programmes for research and innovation and its\u0026nbsp;\u003Ca href=\u0022https:\/\/ec.europa.eu\/info\/research-and-innovation\/research-area\/health-research-and-innovation_en\u0022\u003EHealth\u003C\/a\u003E\u0026nbsp;research policy, supports the development of new treatments and diagnostics for\u0026nbsp;\u003Ca href=\u0022https:\/\/ec.europa.eu\/info\/research-and-innovation\/research-area\/health-research-and-innovation\/rare-diseases_en\u0022\u003Erare diseases\u003C\/a\u003E\u0026nbsp;across Europe.\u003C\/p\u003E\r\n \u003Cp\u003E Under Horizon Europe (2021-2027), the new research and innovation funding programme, a proposed European Partnership on rare diseases is expected to catalyse a systemic transformation in the area. It will coordinate national, local and European research and innovation programmes with the goal of developing diagnostics and treatments to improve the quality of life for people living with rare diseases.\u003C\/p\u003E\n\u003C\/div\u003E\n\u003C\/p\u003E\n\n\u003Ch5\u003EThe research in this article was funded by the EU. 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