For the past 20 years, scientists at the Nencki Institute have been studying rare diseases. “We investigate how specific genetic mutations affect the way cells function. Each year, our understanding of these processes becomes more complete,” says Prof. Mariusz Więckowski, Head of the Laboratory of Mitochondrial Biology and Metabolism at the Nencki Institute. Through a newly awarded NAWA grant, he will help share this knowledge more widely and establish new partnerships with institutions working on rare and ultra-rare diseases.

Prof. Mariusz Więckowski has received funding under the Strategic Partnerships programme of the Polish National Agency for Academic Exchange, NAWA. The aim of the project is to establish a hub at the Nencki Institute that will bring together researchers from different institutions and organisations, including foundations and associations, working to better understand the cellular dysfunctions associated with rare diseases.

These activities may have significant implications for future clinical research focused on identifying biomarkers and molecules that could potentially be used in the treatment of these conditions. They are also highly important from a social perspective, particularly for patients and their families. Rare diseases are often considered a low priority, and developing treatments for them is sometimes seen as economically unviable because of the high costs involved and the small number of patients affected.

Under the definition used in the European Union and Poland, a rare disease affects no more than five in every 10,000 people. It is estimated that between 6,000 and 8,000 rare diseases have already been identified, and new ones continue to be discovered, creating a major challenge for researchers.

“The NAWA grant will allow scientists at every stage of their careers, starting from PhD students, to expand their knowledge of rare diseases. The Nencki Institute is leading the consortium, which also includes the University of Coimbra in Portugal and the University of Ferrara in Italy. Both institutions have worked with us for many years on research into these conditions,” says Prof. Więckowski.

The collaboration between the three institutions is intended to build new international connections and support the exchange of research knowledge and experience. Importantly, it will also involve cooperation with patient foundations representing people and families affected by rare diseases.

“We currently work closely with three such foundations, and two more have recently approached us. We have been collaborating with two of them for several years on diseases including NBIA and PACS2. NBIA, for example, is a neurodegenerative disorder associated with the accumulation of iron in the brain. It has several subtypes, and we focus on three of them for which we have access to material from patients in Poland,” explains Prof. Więckowski.

As part of their research into NBIA, scientists at the Nencki Institute use patients’ fibroblasts, or skin cells, to test different compounds that previous analyses have identified as potentially capable of slowing disease progression.

“To put it very simply, our aim is to determine which of these compounds can make cells collected from patients function more like cells from healthy individuals,” says Prof. Więckowski.

His team is continuing to expand its understanding of the mechanisms underlying rare diseases.

“In MPAN, a subtype of NBIA, there is a mutation in the gene encoding the C19orf12 protein, whose function in the cell is still not fully understood. By comparing cells from patients with MPAN with cells from healthy donors, we can learn more about the role this protein plays,” he explains.

A similar approach is being used in research into the ultra-rare PACS2 syndrome. Scientists at the Nencki Institute are studying fibroblasts obtained from patients, as well as a mouse model of the condition.

“We hope to characterise the disruptions in cellular processes and determine whether restoring these processes could improve cell function, reduce oxidative stress and perhaps even slow disease progression. We are analysing which cellular processes or individual proteins could potentially serve as targets for pharmacological intervention in PACS2 syndrome,” adds Prof. Więckowski.

Existing research also suggests that many neurodegenerative diseases with different genetic causes share similar patterns of cellular dysfunction. This means that an intervention capable of reducing the effects of one disease, potentially in the form of a drug, may also prove useful in other conditions.

Scientists from the Nencki Institute, together with their partners at the University of Ferrara and the University of Coimbra, want to share this knowledge with researchers at other institutions around the world. Although we already know a great deal about rare diseases and the cellular mechanisms behind them, much remains to be discovered.

About the partners

The Nencki Institute of Experimental Biology was established in Warsaw in 1918 on the initiative of Kazimierz Białaszewicz, Edward Flatau and Romuald Minkiewicz. It was named after Marceli Nencki (1847–1901), an eminent Polish chemist, physician and physiologist who worked in Bern and St Petersburg and is regarded as one of the founders of modern biochemistry.

Scientists at the Nencki Institute develop state-of-the-art research methods which, combined with advanced technologies, make it possible to carry out ambitious interdisciplinary projects. The Institute’s research focuses primarily on new therapies and diagnostic methods for neurodegenerative diseases, metabolic disorders, cancer and other conditions affecting human health.

Its scientific work is supported by core facilities which, alongside their own research, provide a broad range of services, including preclinical studies, DNA sequencing, the generation of transgenic animals and biological imaging—from light and electron microscopy to magnetic resonance imaging. The Institute’s innovation strategy has led to a steady increase in the number of publications and inventions protected by Polish and international patents, while also strengthening collaboration with industry.

The University of Ferrara in Italy was founded in 1391 and is home to several dozen research centres. Among them is the Department of Medical Sciences, which plays a key role in both basic and applied research, as well as in advanced education in biomedical and health sciences.

The Department works closely with academics from the University of Ferrara’s biological and pharmaceutical sciences departments, clinicians from local hospitals, and researchers from the biotechnology and pharmaceutical sectors. In recognition of its excellence, it was designated a Department of Excellence for the 2023–2027 period.

As part of this project, the Nencki Institute will collaborate with Prof. Paolo Pinton, a leading expert in general pathology and head of a research group at the Laboratory of Signal Transduction.

The University of Coimbra was founded in 1290 and is the oldest university in Portugal. One of its leading research units is the Center for Neuroscience and Cell Biology, which conducts basic and translational research and provides advanced training in biomedical sciences.

The Center brings together researchers from the university’s faculties of Medicine, Pharmacy and Science, as well as clinical experts from Coimbra University Hospital and partners from the biotechnology and pharmaceutical industries. It also has access to advanced research infrastructure, including specialist facilities for microscopy, mass spectrometry, genomics, brain and behavioural research, electrophysiology and viral vector production.

One of the leading scientists from Coimbra who will collaborate with the Nencki Institute on this project is Prof. Paulo Oliveira, an expert in mitochondrial metabolism and experimental therapies.