Primary sclerosing cholangitis (PSC) is a rare disorder characterized by inflammation and fibrosis of the intra- and/or extra-hepatic bile ducts. PSC leads to cirrhosis, liver transplantation or death in most patients. It is associated with a greatly increased risk to develop hepatobiliary malignancy. To date, there is no therapy for this dreadful disease with a proven benefit on disease progression or tumor development. The pathogenesis of PSC is incompletely understood. Therefore, PSC represents a major unmet clinical need in the field of gastroenterology and Hepatology. 

In order to promote the engagement of young investigators into PSC research and to strengthen the collaboration between existing networks engaged in PSC research, specifically the International PSC Study Group (IPSCSG) and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), we will host a joint workshop for young investigators on basic science and translational immunology in PSC research. The workshop was supported by the Clinical Research Unit 306 (CRU 306), Hamburg, and is open to members of other ERN involved in the respective topic. 

The aims of this workshop were to understand the pathogenesis of PSC, foster networking between basic and clinical scientists as well as between ERNs involved in rare autoimmune and liver diseases (RARE-LIVER, Transplant Child and ERN RITA), and to share knowledge and pool resources between ERNs and IPSCSG. It presented a forum to discuss ongoing research projects between international participants. 

Regenerative Medicine aims to address unmet medical needs by combining our body’s own repair abilities with innovative engineering. 

This technology opens new opportunities for use in urogenital disease. Tissue engineering was adopted by the surgical specialties early this century. One of the first lab-grown organs transplanted into humans was an engineered bladder developed in 2006. Unfortunately, despite initial enthusiasm from both urologists and patients, the lab grown bladder failed to significantly improve bladder compliance, capacity, or detrusor pressure in a phase II trial. 

A major challenge when considering tissue engineering approaches is understanding key properties of the native tissues. An important example where the biomechanics of the native tissue was largely ignored was the introduction of PolyPropyLene (PPL) meshes when treating Pelvic Organ Prolapse (POP). The meshes can cause severe complications (e.g. acute and chronic infections and tissue erosion) and as such are now banned by the FDA for this application. 

These two largely failed attempts to use materials and tissue engineering to treat urogenital disease, left clinicians AND patients with disillusion and an unmet medical need. Our workshop will acknowledge this setback and look out at new developments and technologies to overcome the disillusion and move forward as there is a clear and urgent need for novel biomaterials and functional meshes. The topic was ideal to bring the different stakeholders (patients, clinicians and basic scientists) and different research communities in complex urogenital diseases toge 

DT is defined as a rare benign monoclonal fibroblastic proliferation that arises in soft tissue. They sporadically occur, but 5–20 per cent arise in association with FAP. The incidence of DT is 800-fold to1000-fold higher in patients with FAP than in the general population. Thus, 10–25 per cent of patients with FAP will develop at least one Desmoid Tumour within their lifetime. Desmoid when occur in abdominal cavity is the primary cause of death after colectomy by infiltrating and obstructing nearby structures. 

Contrary to sporadic desmoid tumors whose management has better been defined over the last 10 years the complexity of  DTs treatment in FAP patients still requires to be optimized. 

Several open question about different topics in FAP-related DTs remain to be clarified: 

• Risk prediction and prevention (genotype-phenotype correlation, open vs. laparoscopic preventive surgery) 
• Diagnosis (radiological vs. histological) 
• Treatment strategy (watchful waiting strategy vs. active treatment) 
• Quality of Life 

This workshop aimed to promote further studies and researches on this topic. 

To date, medical treatment (e.g. chemotherapy or immunological therapy) is preferred to surgery, because the surgical trauma is a well-known risk factor of developing further DTs. The medical treatment is based on DTs’ histology; however, a percutaneous biopsy of intra-abdominal DT is not always feasible and a surgical procedure is necessary. 

The creation of a software combining radiological imaging and genetic data, which predicts the nature of intra-abdominal masses in FAP patients would be pivotal in their management and extremely useful for ERN physicians. 

The Workshop aimed to promote networking in the context of two ERNs, EURACAN and GENTURIS, thanks to their mutual focus on DT in FAP, a solid tumor which is both rare and associated to a genetic condition. 

In the context of EJP RD’s ERN Workshops, a workshop on “on Fetal and Postnatal multidisciplinary management in Rare Diseases – Myelomeningocele (MMC) and Lower urinary tract obstruction (LUTO)” was organized by Giovanni Mosiello, Rafal Chrzan, Jean Marie Jouannic, and Giovanni Montini. 

This workshop was addressed to healthcare providers working together with ITHACA, eUROGEN and ERKNet: Foetal surgeon, neonatologist, nephrologist, neurosurgeon, obstetrician, radiologist, paediatric urologist who are involved in the management of MMC and LUTO might be interested to participate in this event. The workshop might have been of a great value for all ERN researchers. 

After more than 20 years of Hereditary breast and ovarian cancer (HBOC) research in Latvia it has been confirmed that at least 5% of unselected breast cancers and 15% of unselected ovarian cancers cases are BRCA1/2 germline pathogenic variant carriers. However, in around 50% cases of HBOC specific family cancer history turned out to be absent and it is impossible to identify cancer free high-risk persons following only traditional diagnostic pathways. Accordingly, HBOC genetic population screening (GPS) is the only way to identify considerable proportion of presymptomatic high risk individuals in order to reduce the proportion of advanced stage breast and ovarian cancers, mortality form this rare disease and the related public spendings. HBOC GPS should be considered as an innovative approach as it has not been introduced in any particular region of Europe so far and there are many psychological, molecular and administrative aspects to be clarified. 

Moreover, in 2022 PSCUH ERN GENTURIS team in collaboration with Riga Stradins University launched the HBOC GPS feasibility pilot project to evaluate the optimal genetic testing strategy and psychometric evaluation of the participants. 

The aim of this workshop was to educate researchers and clinicians on Psychological, molecular and administration aspects of HBOC GPS 
Participants and speakers involved representatives from several ERN GENTURIS partners, including, but not limited to Latvia, Estonia, Lithuania, Poland, Netherlands and Norway. 

The workshop was meant to be on a research method previously developed (“Training in genetics and genomics for primary health care workers”, Dr. E.J.F. Houwink) on how to design and assess effectiveness of a blended training with a focus on rare diseases based on prioritized educational needs, taking hemoglobinopathies as an example. 

During the workshop we wished to explain how to design studies on how to develop training on rare diseases based on exploration and consensus on the role of different rare diseases taking hemoglobinopathies as an example and a blueprint for educational needs on rare diseases as they are perceived by medical care providers, patient advocacy groups and (non)clinical genetics professionals in secondary care. We aimed to submit preliminary research results in an international journal (EJHG), entitled “Exploring and prioritizing future rare diseases education in primary care, taking hemoglobinopathies as an example” and let them serve consecutive steps in our research project Raising awareness for Sickle Cell Disease in Primary Health Care and refer to this workshop held by EJP RD. As stated above, this project is raising awareness for SCD in PHC with two manners of interdisciplinary education and eHealth. the methodology described above could be used by different ERNs for different rare diseases and the blueprint could serve to develop blended trainings on other rare diseases than hemoglobinopathies. We hope we explained the impact the workshop could have on future research on evaluating the effectiveness of the blended trainings on learnt competences. With regards to research on implementation, in the near future we wish to study effectiveness of referrals, but also patient satisfaction with the help received by their primary care professionals, blended care effectiveness on using the flowchart on how the PHC is guided through timelier diagnosing hemoglobinopathy carriers and therefore improved health care of patients with hemoglobinopathies and improved cost effectiveness of people with rare diseases in general. 

Precision medicine is an emerging approach for disease treatment and prevention that accounts for individual’s clinical, physiologic, genetic and sociodemographic characteristics to provide more accurate prediction of disease course and therapy response. 

Monogenic diabetes is an example of how precision diagnosis leads to improvement of disease treatment through genetic testing and Maturity Onset Diabetes of the Young (MODY) is a recognized model of functional precision medicine in clinical practice. However, there are many other rare diseases that could benefit from this aproach. 

This workshop aimed to explore the following: 

• concept of precision medicine 
• clinical implications of genetic diagnosis 
• the case of monogenic diabetes as a learning point to precision medicine 
• application of precision medicine in other rare genetic diseases 
• the challenges of precision medicine in clinical practice 
• research projects of precision medicine applied in other rare diseases 

A final objective was to promote discussion in work groups and stimulate the elaboration of a future research project of precision medicine application and evaluation of its benefits. 

The workshop was aimed at PhD students, clinicians, geneticists and molecular researchers who are involved in rare genetic diseases. 

Advances in gene therapies are completely changing the possibilities we used to have to deal with devastating rare neurological disorders and dramatically changing our expectations regarding outcomes in these patients. More than 50 gene therapies could be in the clinical ground in the next 10 years, but there are still lots of uncertainties and challenges we need to cope with. The aim of this course was to discuss known barriers, challenges, and uncertainties in gene replacement therapies including the vision of different stakeholders (basic researchers, clinicians, patients, regulators, payers, and industry). The course was divided into two days in which we dealt with different bottlenecks. On the first day, we reviewed the state of the art in therapy development and problems of the current viral carriers, and possible solutions. On the second day, we discussed the problems related to clinical implementation and safety. 

Built to protect and preserve the correct functioning of the brain by avoiding the entrance of potentially damaging molecules, the Blood-Brain Barrier (BBB) also prevents small and large therapeutic compounds from efficiently reaching the brain in case of disease. Indeed, the delivery of therapeutics to the brain cells faces many challenges that hinder the development and testing of novel therapies for brain and neurological disorders. Despite this, various strategies are currently being developed to improve the delivery of small and large molecules to the brain.   

The workshop provided an opportunity to present and discuss the most recent advancements in all aspects of research applied to the BBB: from basic biology and pathophysiology to clinical and translational research. The workshop updated all participants on the current and future opportunities for the management and treatment of many neurological disease.  

The event was organised in collaboration with the Brains For Brain Foundation and will provide a unique opportunity for BBB experts from different backgrounds to come together and share their experience and ideas.  
The objectives were the following: 

• Show and discuss recent achievements in basic and clinical research in the fields of neurodegenerative disorders and the blood-brain barrier (BBB). 
• Present and discuss the factors that control the entrance into the brain of drugs and other therapeutic agents which may be helpful in treating central nervous diseases. 
• Discuss novel opportunities for basic, clinical and translational research activities on the BBB. 
• Discuss possible collaborations between scientists, clinicians, patient organisations, and private companies. 

 The workshop was aimed at PhD students, researchers, and clinicians of all levels who are involved in brain and neurological diseases and/or in vascular biology. 

Regenerative medicine and tissue engineering provide strategies to regenerate untreatable diseased organs by either replacing/mimicking the damaged tissues and cells, or boosting their self-healing capacities and modulating the immune response. These topics are at the boundary between RD research and therapy, bridging the scientific advances to the industrial enterprise realm hence ultimately to patients’ bedside. Bone-muscle regenerative strategies include advanced therapies based on stem cells and derivatives, cell reprogramming, immunoregeneration, innovative biomaterials and nanotechnologies, 3D bioprinting and manufacturing techniques. 
This workshop aimed to improve the knowledge and competences on up-do-date regenerative medicine and tissue engineering technologies exploited in the design of advanced therapies for rare diseases affecting skeletal muscles and bones. The topic covers both advanced therapies already in clinical trials and innovative strategies undergoing translational research that merges contributes from a wide range of scientific areas and frontiers technologies. 

The workshop was suitable for the entire ERN community, and brought different professional profiles at the same roundtable, to learn, practice, discuss and share needs, tools and ideas, fostering novel shared paths of development in the RD ecosystem: 

– medical therapies benefit from regenerative medicine and tissue engineering to sustain the functional status of tissues and improve drug efficacy. 
– surgical therapies may implement non-invasive approaches provided by innovative nanotechnologies, 
– PAOs bring the patients perspective and improve their knowledge by keeping up with technological advancements. 

Representatives from ERN-CRANIO and ERN-ReCONNECT partners were involved, including patient advocacy associations with a wide and diversified target audience (PhD students, postDoc, researchers, clinicians, resident fellows, specialized paramedics).