As the EU launches a new €60M call for research in the development of new effective therapies for rare diseases, we talked to award-winning leader in the field, Dr. Daria Julkowska. She is working to bring together a huge and diverse community, connecting up projects and networks to focus progress on these ambitious goals.
“Our goal is that diagnosis, care and treatment should all be available within one year of a patient with a rare disease coming to medical attention.”
Tell us about your path from your PhD in molecular biology and postdoc in cellular biology at the Institut Pasteur, to your leadership role in collaboration now.
I have always been interested in collaborative projects. After about three years of postdoc I couldn’t see myself in the lab looking at the same scientific research topic for years. I wanted to see if there was a different way I could contribute and accelerate research.
I was grateful for the EU – for the chance to study in France – and wanted to know more about how collaborative science works. The study I’d already done gave me a great entry point and I started as a project manager of E-Rare, the ERA-Net for research programmes on rare diseases. It put EU funds to work to better coordinate European research efforts, and better identify gaps and needs in rare disease research.
Was the European Joint Program on Rare Diseases (EJP RD) a natural progression from that project?
My first two years on E-Rare, I had a great boss (Sophie Koutouzov). She got me fully involved so I could understand the rare disease ecosystem and how things are organised at international level. When she left, I felt well prepared to take over.
We started to develop new concepts for collaboration with patient organisations within the European Research Infrastructures. In 2014-2015 we started to implement them, but EU Research Infrastructures were fairly new, it was hard to prove their high value in the RD context.
After some pushing on the funding, the concepts were developed, and in 2016 we were able to think: what’s next, where do we want to go, and we created the EJP RD. It was thanks to the willingness of ERA-Net E-Rare members to become something more, and also the readiness of the European Commission to get engaged and propose something beyond the simple multinational funding mechanism. That’s how the EJP RD adventure started.
We were joined by other important initiatives quite rapidly. The idea was really to take advantage of everything that has been built over the last 15 years – to connect all the different dots and people from funders, universities and research institutions, hospitals, research networks and infrastructures and patients – so that the research functions not as different pieces but all together.
What is the EJP RD working towards?
The vision I share is the one of the International Rare Diseases Research Consortium (IRDiRC) – is that any patient with a rare disease should receive an accurate diagnosis, care and therapy within a year of coming to medical attention, and for the undiagnosed conditions they should be smoothly integrated into the research pipeline.
That’s our objective, and we hope to achieve it by 2027. A secondary goal is to develop 1,000 new therapies for rare diseases within the next eight years, specifically targeting those illnesses that don’t have any treatments.
Each person in the IRDiRC represents institutions committed to the cause. So whatever comes out of its taskforces, be it tools or recommendations, is important. For EJP RD we decided to not to have own scientific strategy committee but to align fully with the strategic vision of IRDiRC as our driver.
Indeed, it makes practical sense to work to one vision, not align multiple strategies, and to have one body doing the thinking and another making things happen. Has there been good progress on this ‘ecosystem approach’ – addressing fragmentation of infrastructures and expertise?
Yes, it’s progressing very well. One of the biggest successes and challenges from the very beginning has been collaboration with European Reference Networks (ERNs). These are networks of clinical experts, providing healthcare, sharing knowledge and clinical expertise on related rare diseases, their diagnosis and treatment, with the aim of developing good practice and most importantly ensuring that it is the expertise that travels to patient and not patient to the expert.
ERNs started around the same time EJP RD did and we organised multiple webinars and spent a lot of time at the beginning to explain our value to these networks. Now, it is real collaborative work – but it has also grown so big it can be a problem to follow everything!
And to put patients at the centre of progress, are you creating a fundamental shift in thinking about scientific research?
If you invest public funding, you should try your best to ensure whatever you finance produces results. But this has not always been the concept for research in general. Often the concept is excellence – but excellent science doesn’t necessarily lead to a product that patients need.
I think that, on that side, we have really advanced, accelerating the translation of research from ‘bench to bedside’. We have also advanced enormously in terms of the involvement of patients in research projects. IRDiRC always encouraged the participation of patients, but there was no detailed monitoring of this or specific support. Since the beginning of EJP RD, we financed the participation of patient organisations in research projects, and created together with EURODIS a guide for patient partnerships in research. It’s mostly aimed at researchers but also at the policymakers and funders, to understand how important it is to engage patients and how they can do that effectively, showing examples.
We have seen some reluctance to involve patients in the past – not because there isn’t the will to do it, but because people are frightened of regulations, or just don’t know how…
We’ve seen this too. [But] in two years EJP RD trained more than 500 people [in safe, effective patient involvement in research] – patients, researchers or clinicians – then we started to build the academic online course; not to replace what is being done, for example by EURODIS or the ERNs, but to sit together, discuss and see where the gaps are and the needs from the community.
What challenges does EJP RD face? Are there plans to scale up?
We were so large from the start, because of the institutions involved. Many of our partners are networks by themselves; all the European research infrastructures are also networks and of course the ERNs, so you really have many layers. There are already 130 institutions in the program, and about 1,400 people working inside it. But it’s ongoing.
We still find it challenging aligning so many different national activities with national plans and a central purpose. We want to get engagement up, especially after the added barriers of COVID-19. Our next steps will involve organising dedicated national events to catalyze discussions. Engaging policymakers and all stakeholders is extremely important for the next phase, which is the Rare Disease Partnership, under Horizon Europe. This will coordinate national, local and European research and innovation programmes, combining research funding and implementation activities supporting research, such as training, data access infrastructures, data standards etc.
Are the benefits coming through for patients as expected?
Patients can now accompany researchers more closely than before – they can follow everything and help in some way in the translation of results [to real-world diagnostics, treatments, or therapies] but the reality is, the benefit really depends on what the objective of the project is. I think that in general, the impact of the EJP RD is really the structural impact – the organisation of research and the fact that we really accelerate those connections and this is really very precious for the community. The Horizon Europe programme has a dedicated call on Rare Disease that opened in October and further opportunities for targeting rare diseases across other topic areas. That is a good thing.
A lot of patient groups say there’s a need for research around mental wellbeing of rare disease communities – not just patients, but carers and people around them too. Are those needs reflected in your remit?
Yes, we recently closed a dedicated call focused on social sciences and humanities, which expands through all those things – health economics, wellbeing, the burden of rare diseases. We had 40-50 applications, where the typical rate in rare disease research would be 200-250, but still it’s a great success. As long as ten years ago we were speaking about this very important need and it’s taken this time to filter through to the funding, so we are excited to see the results. I was also contacted by the European Burden of Disease Cost Action , which is focusing on the burden of diseases, so we are going to try to work on this together because I think the topic is extremely important, extremely interesting and connects to plenty of other things like patient-reported outcomes.
With more funding for research and networks, there’s lots of new data. It has been recognised that access to good data accelerates research. How does EJP RD support that?
For funded research projects we specify the platforms where they can go and deposit their data. We also now ask for a data management plan from all the projects that are financed. From the very beginning they promise that their data will be shared.
First of all though, to accelerate research and re-use of data you have to have the capacity to connect the different types of resources, so this is what we are doing. What we expect is that at the end of the EJP RD we will have the first fully functional version of the Virtual Platform, where you will have catalogue resources that will be connected and that you will be able to search and reuse. We are making RD and non-RD resources speak to each other to speed up data sharing and analysis across international research and rare disease data hubs like ORPHANET, ELIXIR and RD-CONNECT.
We are also in a lot of discussions with the European Health Data Space, because now things are also engaged at the European level, so collaboration is very important to anchor the rare diseases community and mutualise the efforts and resources.
And what about patient access to data? We co-developed the Duchenne Data Platform (DDP) as part of VISION DMD as we know it’s an emotive issue for some patient groups.
It’s getting better and better, but we’re not there yet. It needs to be conceptualised, not just patient access but ownership of data. Patients participate very actively in EJP RD including the development of the virtual platform, looking at their activities and their propositions on the use cases, etc. But I would like to see more.
We’re very involved, along with the ERNs and registries, on getting patient consent right, and how it translates across countries, and we’ve advanced hugely on this, developing an enhanced model of informed consent that’s manageable to give – not 60 pages of form filling – but ticks necessary legal boxes in different contexts.
This is not just about holding your data, if you are a rare disease patient you want control of it so it can be used again and it’s about the patient making their data accessible for future research projects. This is not a trivial thing to solve.
Industry is important for translating research from ‘bench to bedside’. Where does industry sit among your projects?
The EJP co-fund instrument imposes the exclusion of industry as full partners, which is a pity but we do engage with the industry at several levels. Within our Policy Board EFPIA, EUROPABIO or EUCOPE have their own representatives providing strategic input. Industry with patient input has helped develop and co-finance rare disease research challenges. This is delivering rapid highly focussed research and innovation to go faster to develop specific products, for example developing an intranasal medical device for newborns. The new Rare Disease Partnership is very different, collaboration with industry will be more integrated, building on our existing dialogue.
The concept of a research project can be very different for SMEs, especially in terms of time scales. SMEs cannot wait one year from preparing your grant applications, to the moment that you are going to receive a response and then another six months to get your first money. Working with companies and especially with the SMEs requires a specific concept of tools and funding, which is different to our approach to academic research.
How did it feel when you recently won the Black Pearl European Rare Disease Leadership Award?
It was a huge surprise and very emotional, as you have to do something big to support the rare disease community, and from my standpoint I was just a beginner. It was a great boost to feel what I was doing was recognised. I see every day that the rare disease community is really very special – it touches you, there is a commitment that goes beyond other medical domains.
I see myself as supporting and accompanying that community. One role of the EJP RD is to show that this community is one of the flagships; our concepts can be translated to other diseases or more generally. We have always worked on identifying barriers for the industry to get engaged with rare diseases – it can still be a challenge. There has to be a higher level of inclusiveness, extending to funding. Because when you realise you have a disease but there is not a single research project around it, it is really not encouraging. I think you need to make sure that really no one is left behind.
This interview was conducted by Vision DMD Project Manager Dr Ritchie Head (Ceratium). Many thanks to Dr. Daria Julkowska for her time, openness and enthusiasm during our discussion.
VISION-DMD is a collaborative global project that aims to develop a safe, effective and affordable therapy for Duchenne Muscular Dystrophy (DMD)by investigating the safety and efficacy of Vamolorone (VBP15). Further to data discussion in this interview, this project has already returned patient data, having co-developed the Duchenne Data Platform (DDP). This is a patient-led registry created in 2019 and managed by Duchenne Parent Project in the Netherlands. A FAIR version of the Platform is being refined ready to be linked to the EURO-NMD registry hub. This will facilitate future research of Duchenne across multiple teams and projects.
The EJP RD Joint Transnational Calls in 2019 and 2020 funded 40 research projects for a total sum of 55 M€. Three of these projects focus on neuro-muscular diseases, one additional project looks at non-muscular actinopathies. You can find more details about them here: Website link: https://www.ejprarediseases.org/our-actions-and-services/funding-opportunities/funded-projects/