The contribution of the EJP RD to the improvement of lives of RD patients by providing new and optimised treatment options and diagnostic tools will be achieved as a sum of efforts provided within different pillars and transversal activities strengthened by the central coordination and close linkage with relevant policy stakeholders to translate these efforts at regional, national and EU levels.
New and optimised treatment options and diagnostic tools can only emerge from well-organized, coordinated science that includes basic, translational, clinical social and health economic research. These different types of research will be financed and closely monitored in Pillar 1 thereby accelerating development of diagnostic tools and treatments.
Pillar 2 aims at removing obstacles, for both humans and computers, to finding, accessing under welldefined conditions, analysing and reusing data across the many resources that are relevant for clinical and biological research on rare diseases. The power of Pillar 2 virtual platform will lie in enabling RD data and tool providers to make their data as usable as possible through FAIR principles. RD researchers and experts will be able to find and exploit most relevant data and tools more rapidly to perform advanced and reproducible analysis allowing better understanding of RD causes, mechanisms and determinants, which will improve ways to diagnose and to treat RD.
The successful delivery and implementation of Pillar 3 training courses will result in the systematic implication of patient representatives in the design of research, treatment strategies and developments, as well as care programming and actions at European, national and regional levels.
By creating an end-to-end pipeline of support and expertise for RD research, Pillar 4’s focus on translating excellent science into effective interventions for RD patients will maximise the patient impact of the EJP RD efforts. By ensuring access to expertise, facilities and funding, the complexities to translation will be ameliorated, while the efforts to develop, demonstrate and disseminate improved clinical study methodologies with a support desk available will substantially improve our ability to develop valuable interventions for small populations and enhance the involvement of ERNs in clinical studies.
Yearly updates on impact 1
In progress, see year 2
- EJP RD invested 30.5 M€ in 22 research projects fostering acceleration of diagnosis and/or exploring disease progression and mechanisms of rare diseases and 24.5 M€ in 18 research projects focusing on Pre-clinical research to develop effective therapies for rare diseases. Importantly, these research projects (8/22 and 14/18) profit from the direct engagement of rare diseases patients (EJP RD is funding Patient Advocacy Organisations) participating in the design of research, treatment strategies and outreach activities. This implication is key to accelerate the development of new and optimised treatment options and diagnostic tools. Furthermore, half of the “translational” project targeting the development of new therapies were mentored during their application process (applicants applied for the service on a voluntary basis) and this free innovation mentoring support will follow during their lifetime maximising their translational potential and uptake of results.
- The mentoring service ensured within EJP RD by EATRIS has been uptaken by the European Commission to follow up EC-funded rare diseases projects. This is a major step demonstrating that proof-of-concept solutions developed within the ecosystem created by EJP RD are expanded and used at larger scale for the benefit of RD community.
- The work of EJP RD on demonstration and innovation in methodologies for clinical studies in small populations resulted in direct collaboration with the European Medicines Agency. The pathways for validation of novel proposed methodologies are now being considered, which will improve the design of clinical studies and accelerate the delivery of new treatment options on the market.
- Pillar 2 has produced a considerable amount of data for cross-omics analysis (68 pathways) aimed at improving the knowledge about RD. 3 case-studies applying networks combining several pathways are being tested to improve and accelerate disease diagnostics.
- EJP RD financed 12 research projects with 11.5 M€ in the field of social sciences and humanities that aim improving the lives of RD patients by providing evidence of economic, psycho-social impacts and overall burden of rare diseases, as well as improving health and social care services and use of innovative technology systems in healthcare practice.
- WikiPathways, the database for molecular pathways contains 90 rare disease pathways. The Network approaches that target improving and accelerating rare disease diagnostics by combining several pathways and testing them with multiomic data are progressing and being expanded to include genetic variants information and nutritional data. The relating multi-omics analysis workflows on Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) has been containerized to be provided through the VP for reuse and reproducibility.
- Variant interpretation tools and interfaces have been enhanced enabling accurate variant interpretation (for rare diseases diagnosis).
EJP RD implemented Joint Transnational Call 2022 that fostered the Development of new analytic tools and pathways to accelerate diagnosis and facilitate diagnostic monitoring of rare diseases. 12 multinational consortia with a foreseen budget of about 17 Mio € were selected for funding. The funded projects cover wide range of rare diseases and target different types of diagnostic tools spanning from molecular diagnosis and biomarkers, through multi-omics approaches to the development of dedicated monitoring, imaging tools or in vivo metabolic tests. The EJP RD WikiPathways, the database for rare diseases molecular pathways contains now 110 RD pathways. The Network approaches that target improving and accelerating rare disease diagnostics by combining several pathways and testing them with multiomic data (metabolomics, proteomics, peptidomics, transcriptomics and genetic variants) progressed using both data-driven and prior knowledge-driven methods. The relating multi-omics analysis workflows on Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) has been containerized to be provided through the VP for reuse and reproducibility. The work on The Huntington’s Disease demonstrated that different collaborative network analysis methods are able to pick the main disease signal while some methods can identify pathways that were not discovered by other methods; these results trigger new hypotheses that can lead to the discovery of new knowledge in the field. The network analysis of the Inclusion Body Myositis identified five subnetworks that are hypothesized to be involved in the pathogenesis; a complex federated analysis using publicly available human datasets is being conducted to test the robustness of these subnetworks. Finally, variant interpretation tools and interfaces have been further enhanced enabling accurate variant interpretation for rare diseases diagnosis.
EJP RD continued to contribute to the acceleration of diagnosis and treatments for rare diseases patients by supporting research projects through its fifth Joint transnational Call (JTC 2023) with the topic “Natural History Studies addressing unmet needs in Rare Diseases”. Launched in November 2022 with participation of 21 funders from 16 countries it delivered 13 consortia with a foreseen budget of about 19 Mio € were selected for funding. The funded projects cover wide range of rare diseases and target different types of diagnostic tools spanning from molecular diagnosis and biomarkers, through multi-omics approaches to the development of dedicated monitoring, imaging tools or in vivo metabolic tests.
The EJP RD WikiPathways – the knowledge for rare diseases molecular pathways, now includes 115 rare disease pathways that target improving and accelerating rare disease diagnostics by combining several pathways and testing them with multi-omic data (metabolomics, proteomics, peptidomics, transcriptomics and genetic variants) progressed using both data-driven and prior knowledge-driven methods. Three case studies (kidney malformations, Huntington’s disease, Inclusion Body Myositis) enabled demonstration of the usability and validity of the proposed RD pathways in different conditions and for different questions. All the developed analytical workflows can be reused as a method to study disease mechanisms involved in other diseases when multiple omics datasets are available. Moreover, variant interpretation tools and interfaces have been further enhanced helping the interpretation of the large numbers of variants of unknown significance currently being identified for rare diseases diagnosis. Finally, the developed Python package “ODAMNet” allows to identify the possible associations between chemicals and rare diseases systematically and the generation of hypotheses for further investigation of effect mechanisms.