Predoctoral researcher Lourdes Ailen Arena, a member of the Oncogenesis and Antitumor Drugs group at the Sant Pau Research Institute (IR Sant Pau), has been awarded a prestigious INPhINIT predoctoral fellowship from the ”la Caixa” Foundation. The fellowship allows her to pursue her doctoral thesis as part of an innovative research project in cancer nanoimmunotherapy. The award ceremony was held on Tuesday, March 18, and this was the only fellowship granted to IR Sant Pau in this edition.

Pioneering Cancer Nanoimmunotherapy Research

Arena’s research at IR Sant Pau is part of an ambitious project focused on targeted nanoimmunotherapy against CXCR4+ cancer stem cells, a cutting-edge area in oncology. These cells represent a subpopulation within tumors with a high capacity for self-renewal, resistance to conventional treatments, and metastatic potential—making them a top target in the fight against cancer.

High expression of the CXCR4 receptor on their surface is associated with more aggressive tumors and lower patient survival rates, as this receptor plays a key role in tumor proliferation, invasion, and metastasis. This research project aims to attack these cells directly, reducing the risk of recurrence and improving treatment outcomes. The doctoral thesis will be supervised by Dr. Ugutz Unzueta, a researcher in the Oncogenesis and Antitumor Drugs group.

The goal of the project is to develop a novel therapeutic strategy using protein-based nanoparticles selectively targeted at cancer stem cells. The research aims to design a highly efficient nanoparticle that delivers an innovative drug inside these cells, inducing immunogenic cell death. This mechanism triggers the body’s immune response against the tumor, delivering a dual effect: specifically eliminating cancer stem cells and activating the immune system to fight cancer more effectively.

The project builds on previous advances made by the IR Sant Pau group in the development of multivalent, superselective nanoparticles—a patented technology that has shown great promise in targeted cancer therapy. The research will combine in vitro, ex vivo, and in vivo studies, enabling the evaluation of antitumor efficacy and immune activation in animal models of CXCR4+ tumors.

A Leading Environment in Cancer Research

The Oncogenesis and Antitumor Drugs group at IR Sant Pau is a multidisciplinary unit specializing in the development of new nanomedicines for cancer treatment. Their work focuses on using advanced technologies to enhance the effectiveness and safety of antitumor therapies. The group is part of the Spanish excellence network CIBER-BBN and works closely with clinicians at Sant Pau Hospital, strengthening translational research with direct clinical applications.

Arena’s recognition with the INPhINIT fellowship from ”la Caixa” highlights the value of young talent in biomedical research and further establishes IR Sant Pau as a reference center in cutting-edge cancer research.

A research team led by Dr. Josep Francesc Nomdedeu, head of the Hematologic Diagnostics Research Group at the Sant Pau Research Institute (IR Sant Pau) and hematologist at the Sant Pau Hospital’s Hematology Laboratory, in collaboration with the Universitat Autònoma de Barcelona, the University of Barcelona, the Cancer Research Center of Marseille (INSERM), and other institutions, has identified a previously underexplored mechanism by which the KIT D816V mutation reprograms cellular metabolism to promote tumor development.

The study, recently published in the journal Experimental Hematology, shows that the KIT D816V mutation—frequently found in hematologic malignancies such as acute myeloid leukemia (AML) and systemic mastocytosis—increases both the number and activity of mitochondria while simultaneously reducing their physiological clearance through mitophagy. Mitophagy is a selective cellular cleanup process through which damaged or unneeded mitochondria are eliminated to maintain metabolic balance and prevent the buildup of harmful free radicals. The central mechanism behind this disruption involves the downregulation of the BNIP3 gene, a key regulator of mitochondrial autophagy.

To investigate the impact of the KIT D816V mutation, researchers used two human myeloid cell lines: ROSA (mast cell-like) and TF-1 (erythroleukemia). They compared the behavior of mutated cells to their wild-type (non-mutated) counterparts.

The team analyzed various biochemical and cellular parameters to assess mitochondrial function, including oxygen consumption, ATP production, mitochondrial membrane potential, and reactive oxygen species (ROS) generation. They also measured the number, size, and morphology of mitochondria, along with the expression of critical markers related to autophagy and mitophagy—such as BNIP3 and LC3—using electron microscopy, flow cytometry, qPCR, and immunoblotting.

To confirm the clinical relevance of these findings, researchers analyzed samples from AML patients to determine whether those with the KIT D816V mutation also showed reduced BNIP3 levels. Indeed, this association was observed.

A Shift in Cellular Energy Metabolism

Unlike many other cancers that rely primarily on glycolysis—a fast but less efficient metabolic process that generates energy from glucose without requiring oxygen—this study found that KIT D816V-mutant cells favor mitochondrial oxidative phosphorylation (OXPHOS) to produce energy. This shift results in increased ATP production, heightened mitochondrial respiration, and elevated levels of ROS such as superoxide, which can damage DNA and contribute to genomic instability.

The researchers found that this functional shift is directly linked to lower levels of BNIP3, a protein that serves as a signal for the selective degradation of defective mitochondria. Its loss leads to an accumulation of mitochondria that are active but dysfunctional, potentially increasing oxidative stress and promoting tumor progression.

In patient-derived AML samples, those harboring the KIT D816V mutation exhibited significantly lower BNIP3 levels, which were associated with worse overall survival.

mTOR: A Constantly Activated Growth Pathway

The study also revealed that the mTOR pathway—one of the primary regulators of autophagy—is constitutively activated in mutant cells, even under nutrient-deprived or growth factor-deficient conditions. This autonomous function reflects a loss of dependence on external signals, a hallmark of many cancer cells.

“The KIT D816V mutation acts as a double accelerator: it boosts cellular energy production through mitochondria while also blocking their natural elimination,” said Dr. Josep F. Nomdedeu. “This imbalance could pave the way for new therapeutic strategies aimed at restoring control over mitochondrial function.”

Therapeutic Outlook

The findings suggest that restoring BNIP3 expression could be a viable strategy to counteract the pro-tumor effects of the KIT mutation. In in vitro experiments, overexpression of BNIP3 reinstated mitophagy and reduced the number of mitochondria in mutant cells.

This discovery opens new avenues for research and potential therapeutic targets in hematologic malignancies driven by KIT mutations, particularly in patients who are resistant to conventional treatments.

Institutional Support

This study was supported by multiple national and international research institutions. In Spain, funding came from the Carlos III Health Institute through projects PI13/2729 and PI16/094, and from the Generalitat de Catalunya via grants 2014-SGR-383, 2017-SGR-1395, and the PERIS program SLT 002/16/0043.

Internationally, the research was funded by Aix-Marseille University, the Amidex Foundation, Canceropôle Provence-Alpes-Côte d’Azur, the French National Cancer Institute (INCa), and the Provence-Alpes-Côte d’Azur Region, highlighting the collaborative and translational nature of the project.

Reference:

Cisa-Wieczorek S, Hernández-Alvarez MI, Parreño M, Muñoz JP, Bussaglia E, Carricondo M, Ubeda J, Dubreuil P, Zorzano A, Brenet F, Nomdedeu JF. D816V KIT mutation induces mitochondrial morphologic and functional changes through BNIP3 downregulation in human myeloid cell lines ROSA and TF-1. Exp Hematol. 2025;145:104748. https://doi.org/10.1016/j.exphem.2025.104748

A study published in Cardiovascular Diabetology shows how detailed analysis of lipoproteins and glycoproteins can help predict cardiovascular risk in people with type 2 diabetes (T2D). Using advanced magnetic resonance imaging (MRI) technology, the research team identified plasma alterations associated with increased risk in these patients.

This collaborative work was led by teams from CIBER in its areas of Diabetes and Associated Metabolic Diseases (CIBERDEM) and Physiology of Obesity and Nutrition (CIBEROBN), at the Institut de Recerca Sant Pau (IR Sant Pau) and the Institut d’Investigació Sanitària Pere Virgili (IISPV).

The study is part of the LIPOCAT project and analysed a total of 933 patients with T2D from four Spanish cohorts. “Traditional risk factors do not predict cardiovascular events with sufficient accuracy in people with type 2 diabetes. We aimed to evaluate whether incorporating advanced lipoprotein profiling via MRI could enhance the predictive capacity of conventional models,” explains Dr Dídac Mauricio, principal investigator of the study, affiliated with IR Sant Pau and CIBERDEM.

The results show that certain lipoprotein alterations, such as triglyceride content in remnant and LDL particles, along with inflammatory markers, are associated with a higher risk of cardiovascular events. “Incorporating these measures into traditional models significantly improves predictive accuracy, with an increase in the area under the ROC curve (AUROC) up to 0.76 in the internal validation cohort,” highlights Dr Núria Amigó, first author of the study and CIBER researcher at the Institut d’Investigació Sanitària Pere Virgili (IISPV).

These findings could have clinical implications by enabling better cardiovascular risk stratification in patients with type 2 diabetes and allowing for a more personalised management approach. “Advanced lipoprotein profiling technology could become a key tool in improving cardiovascular prevention in this population,” concludes Dr Amigó.

The study involved researchers from Hospital de Sant Pau and Hospital Clínic de Barcelona, Hospital Universitari Arnau de Vilanova (Lleida), IDIAP Jordi Gol, Universitat Rovira i Virgili (Tarragona), and Hospital Universitari Germans Trias i Pujol, in collaboration with Washington University School of Medicine. It was led by Dr Dídac Mauricio.

Article Reference:
Amigó N, Castelblanco E, Julve J, et al. Advanced Serum Lipoprotein and Glycoprotein Profiling for Cardiovascular Event Prediction in Type 2 Diabetes Mellitus: The LIPOCAT Study. Cardiovasc Diabetol (2025) 24:88. DOI: 10.1186/s12933-025-02636-5.

Sleep disorders are highly prevalent among people with Down syndrome, yet they often go undiagnosed. Researchers at the Sant Pau Research Institute (IR Sant Pau) are conducting a pioneering study to examine how these disturbances may influence the development of Alzheimer’s disease, aiming to improve early detection and treatment for these patients.

Groundbreaking Study Explores Connection Between Sleep and Neurodegeneration

The Sant Pau Alzheimer-Down Unit, in collaboration with New York University, has launched a study using advanced techniques such as polysomnography and central temperature monitoring via a special ingestible capsule. These methods will help analyse how the sleep disturbances and circadian rhythm disruptions may affect Alzheimer’s progression in individuals with Down syndrome.

Dr Lídia Vaqué, a researcher from the Neurobiology of Dementia group at IR Sant Pau, explained: “We know that poor sleep can have a direct impact on neurodegeneration, but we need more data to determine to what extent this can be modified through specific interventions.” The study will also provide long-term monitoring of patients to identify preventive strategies and improve their quality of life.

Need to Detect and Treat Sleep Disorders in People With Down Syndrome

Sleep disorders are particularly common among people with Down syndrome, yet they frequently go unnoticed. Dr Sandra Giménez, a clinical neurophysiologist specialising in sleep medicine at Sant Pau’s Multidisciplinary Sleep Unit, said: “Sleep disorders in people with Down syndrome are highly prevalent and, unfortunately, frequently overlooked. Sleep apnoea, for example, is one of the most common conditions and can have serious consequences if left undiagnosed and untreated.”

The lack of early detection means that many people with Down syndrome do not receive the appropriate treatment or are wrongly assumed to be unable to tolerate it. However, the team at the Sant Pau Sleep Unit, which also includes Dr Inés Podzmaczer, Dr Vera Lugo and Dr Ana Fortuna, as well as the nursing team, has demonstrated that treatment with continuous positive airway pressure (CPAP) devices is just as effective in this group as in the general population, improving sleep quality and reducing associated risks.

“It is crucial to raise awareness among families and healthcare professionals about these disorders because sleep not only affects daily life but also has long-term health implications,” Dr Giménez added.

Call for Participants in Alzheimer’s and Sleep Study

The study aims to recruit 60 participants for long-term monitoring of Alzheimer’s biomarkers. Those taking part will undergo a comprehensive sleep assessment, as well as neuropsychological and high-precision brain imaging tests.

The Sant Pau Research Institute is inviting people with Down syndrome and their families to participate in this research, which will not only contribute to scientific knowledge but could also have a direct impact on their quality of life.

For more information on how to take part in the study, please contact the research team at Sant Pau Research Institute.

Medical Research Drives Inclusion and Innovation in Down Syndrome

To mark World Down Syndrome Day, the Jérôme Lejeune Foundation – an international organisation dedicated to research, medical care and the defence of the rights of people with genetic intellectual disabilities – has coordinated an initiative with scientists from the T21 Research Society, a global network of researchers specialising in Down syndrome.

Among the scientists involved are Dr Juan Fortea and Dr Maria Carmona-Iragui, who have highlighted the crucial role of scientific research in improving health outcomes and promoting inclusion for people with Down syndrome.

The initiative points out that, despite scientific advancements increasing life expectancy for this group to around 60 years in some countries, research in the field remains underfunded. In Europe, support is limited compared with the United States, where the INCLUDE programme has allocated over $400 million to Down syndrome research.

Studying conditions such as sleep disorders, autoimmune diseases and Alzheimer’s could lead to major breakthroughs not only for people with Down syndrome but for the wider population. With greater investment and institutional support, research can continue to advance, ensuring a better quality of life and real inclusion for this group.

Sant Pau Leads Research on Down Syndrome and Alzheimer’s

Sant Pau Research Institute has been a pioneer in Spain, establishing the Alzheimer-Down Unit in December 2014 in collaboration with the Catalan Down Syndrome Foundation. Recognised by the Catalan government, this multidisciplinary unit is a reference centre in Catalonia for neurological conditions associated with Down syndrome, combining clinical and translational research to address the specific needs of this group.

Recently, Sant Pau researchers identified a link between cerebrovascular lesions and the development of Alzheimer’s in people with Down syndrome. This discovery underscores the importance of vascular health in disease progression and could open new avenues for preventive and therapeutic strategies tailored to this population.

A team from the Sant Pau Research Institute (IR Sant Pau) has conducted a comprehensive review of the impact of sex on the progression of genetically determined Alzheimer’s disease, including autosomal dominant Alzheimer’s disease (ADAD), Down syndrome-associated Alzheimer’s disease (DSAD), and APOE4 homozygosity. The study, published in Frontiers in Aging Neuroscience and led by Dr Laura del Hoyo, a Miguel Servet researcher in the Neurobiology of Dementia group at IR Sant Pau, concludes that while sex influences certain cognitive and structural aspects of the brain, its effects on disease progression are far less pronounced than in sporadic Alzheimer’s.

According to Dr del Hoyo, “Sexual dimorphism is one thing, but how sex impacts Alzheimer’s disease progression is another. In genetically determined Alzheimer’s, genetics play such a significant role that we do not see major differences between men and women in disease progression, unlike in the sporadic form.” However, the study identifies some exceptions that may be linked to differences in cognitive reserve.

Sex Differences in the Progression of Genetic Alzheimer’s

The review examined studies analysing the impact of sex on three fundamental aspects defining genetically determined Alzheimer’s: disease penetrance (i.e., the proportion of individuals with a specific genetic mutation who develop the associated clinical symptoms), the age of symptom onset, and the clinical progression and evolution of key biomarkers such as amyloid accumulation, tau pathology, and neurodegeneration.

The results showed that in all forms of genetic Alzheimer’s, sex differences in these three aspects were subtle or non-existent, although some specific patterns emerged. In ADAD, the reviewed studies indicated that women in advanced disease stages exhibited greater neurodegeneration, with more pronounced cortical thinning and a reduction in hippocampal and amygdala volume compared to men. Despite these structural changes, their cognitive performance remained similar, suggesting that they may have greater cognitive reserve, which helps protect against pathological progression.

In the case of DSAD, the results were relatively different. Women carrying the APOE4 gene tended to develop dementia symptoms earlier than men with the same genetic predisposition. Additionally, this group showed higher amyloid accumulation and increased neurodegeneration compared to men. These findings contrast with observations in ADAD and APOE4 homozygosity, where no significant sex differences were found in disease progression.

“In Down syndrome, carrying APOE4 seems to have a greater impact on women than on men in terms of amyloid accumulation and neurodegeneration,” explains the researcher. However, she clarifies, “We cannot say that the effect of this gene is generally more detrimental in women than in men because we have not consistently observed this.”

Why Are Gender Differences Less Marked in Genetic Alzheimer’s?

One of the key findings of this review is that, unlike sporadic Alzheimer’s, where women show higher prevalence and faster disease progression, genetic Alzheimer’s follows more predictable patterns and is less influenced by sex. As Dr del Hoyo explains, “Genetics creates so much noise that the role of sex becomes diluted.” However, this does not mean that underlying differences do not influence how the disease manifests in each individual.

Sexual dimorphism is evident in aspects such as cognitive performance before disease onset. Women are generally better at verbal memory tasks, while men tend to perform better in visuospatial tasks. This is significant because it may mask early signs of decline in women, making early detection more challenging, as most diagnostic tools rely on language-dependent tests.

“If all the assessment tools we use rely heavily on language, we might be underestimating early deficits in women, as they have a pre-existing advantage in this domain,” warns the researcher. This testing bias could lead to later detection of symptoms in women, posing a challenge for research and clinical practice. In this regard, the study highlights the need to develop more balanced assessment tools that account for sex differences and enable more accurate and equitable detection of cognitive decline in the early stages of the disease.

Further Research with a Gender Perspective

Beyond the findings on genetic Alzheimer’s progression, the study emphasises the importance of continuing to investigate these differences using more refined methodologies. Longitudinal studies, which follow patients over time, are essential tools for better understanding the effects of sex on the disease. The need to diversify cognitive assessment methods is also highlighted, incorporating tests that do not rely solely on skills where one sex may have an initial advantage. Additionally, a new line of research is emerging on the role of hormones, particularly in Alzheimer’s in people with Down syndrome, as early menopause in women with this condition may influence disease progression.

One of the study’s key points is the importance of communicating results rigorously and avoiding bias in data interpretation. “There has been some ‘cherry-picking’ in gender studies, highlighting only findings where differences are observed and overlooking ‘null results’. But it is just as important to report when we do not find differences. Communicating ‘null results’ well is crucial for gender-sensitive research that is based on solid scientific evidence,” emphasises Dr del Hoyo.

This study represents a significant step forward in understanding the impact of sex on genetic Alzheimer’s and raises new questions about how to tailor diagnostic and treatment strategies to the individual characteristics of each patient. Although sex differences in disease progression are subtle, studying them could help improve accuracy in detection and the management of Alzheimer’s in populations with genetic predisposition.

Reference Article:

Del Hoyo Soriano L, Wagemann O, Bejanin A, Levin J, Fortea J. Sex-related differences in genetically determined Alzheimer’s disease. Front Aging Neurosci 2025;17. https://doi.org/10.3389/fnagi.2025.1522434.

On April 4th and 5th, the Modernist Complex of the Sant Pau Hospital will become the meeting point for the third edition of “Entre Dones”, an event to talk, share, and learn about women’s health from a gender perspective.

Scientific Day – April 4th

On Friday, April 4th, from 2:00 p.m. to 5:30 p.m., at the Pau Gil Room of the Sant Pau Modernist Complex, we will hold the Scientific Day, dedicated to cardiovascular diseases and risks from a gender perspective.

Cardiovascular diseases are the leading cause of death among women, but they remain underdiagnosed and poorly researched, seriously affecting their health and quality of life. Additionally, hormonal and reproductive factors play a key role.

This event is aimed at:

• Specialists in Family and Community Medicine, Obstetrics and Gynecology, Cardiology, Anesthesiology and Resuscitation, Emergency Medicine, and anyone interested in gender-focused medicine.
• Midwives and primary care nurses.
• Community Pharmacists and Hospital Pharmacists.

Check out the full program here.

Register for the Scientific Day here.

Registration: 30 euros

Participatory Day – April 5th

On Saturday, April 5th, come enjoy a morning dedicated to women’s health at the Sant Pau Modernist Complex. A day to break taboos, resolve doubts, and take steps toward a fairer and more inclusive medicine.

Enjoy a wide range of activities focused on major thematic areas: cardiology, gynecology, and a space dedicated to children, Between Girls (6 to 12 years old).

Additionally, throughout the morning, the Gardens of the Sant Pau Modernist Complex will come alive with outdoor activities. There will be several stalls, all the result of projects committed to sustainability and gender perspectives.

Check out the full program of activities here.

Register for the participatory event here.

We look forward to seeing you!

A recent study on the functions of human protein-coding genes, published in the prestigious journal Nature, marks a significant advancement in the functional characterisation of the human genome. The research was conducted by an international team of scientists, including Dr Àlex Bayés from the Sant Pau Research Institute (IR Sant Pau), the sole investigator from a Spanish research centre involved in the project.

The study presents the most comprehensive compilation to date of human gene functions, effectively forming what could be termed the human functionome. This invaluable source of information holds profound implications for both basic and biomedical research.

An Evolutionary Approach to Understanding Human Gene Function

The project integrates data obtained directly from human gene studies with a comparative evolutionary analysis. This methodological approach has enabled researchers to infer nearly 70,000 functions, covering 82% of human genes. Previous studies had identified functions for only 40–60% of protein-coding human genes. Notably, around 60% of these inferred functions stem from the evolutionary approach applied in this study.

Furthermore, the evolutionary study has provided insights into the origins of human gene functions. Paradoxically, the findings suggest that most of these functions are highly ancestral, predating the emergence of multicellular organisms more than 1.6 billion years ago, and have remained largely conserved throughout this period. The last major evolutionary wave of new functions is believed to have occurred with the emergence of placental mammals around 100 million years ago. Since then, few new functions have been added to the human genome’s repertoire.

This work was made possible through the support of PAN-GO (Phylogenetic Annotation of Gene Ontology), an innovative platform that integrates phylogenetic data to enhance the precision of functional gene descriptions. The use of PAN-GO has been instrumental in identifying evolutionary patterns in gene function and in generating a more complete and accurate compendium of gene roles in human biology.

Boosting Biomedical Research in Spain

The participation of IR Sant Pau in this study reaffirms the institute’s scientific excellence and its contribution to cutting-edge basic and biomedical research on a global scale. Collaborating in such projects strengthens the role of Spanish science in high-impact international initiatives.

“We have had the tremendous privilege of contributing to a global scientific initiative aimed at systematising the knowledge generated by the scientific community on human gene functions, creating indispensable computational analysis tools for biomedical research,” said Dr Bayés.

Reference Article

Feuermann M, Mi H, Gaudet P, Muruganujan A, Lewis SE, Ebert D, et al. A compendium of human gene functions derived from evolutionary modelling. Nature 2025:1–9. https://doi.org/10.1038/s41586-025-08592-0

This Monday, 10 March, a workshop with the Da Vinci surgical robot was held at the Institut de Recerca Sant Pau (IR Sant Pau), taking place in the centre’s animal facility. The event brought together ten doctors from various hospitals across Catalonia. This initiative allowed healthcare professionals to familiarise themselves with this cutting-edge technology, which represents a revolution in the field of robot-assisted surgery.

During the session, participants had the opportunity to gain first-hand experience of the Da Vinci robot’s functionalities, exploring its operation and applications in the surgical field. Through practical exercises and demonstrations, the doctors were able to handle the console and experience the precision of movements assisted by this high-tech robotic system. The primary objective of this activity was to provide a realistic immersion into the robot’s capabilities and its impact on improving surgical procedures, reducing the margin of error and promoting faster recovery for patients.

This workshop is part of a regular training programme held at the centre’s animal facility, covering various aspects related to this precision tool. On previous occasions, specific sessions have been organised on advanced surgical techniques, the handling of high-precision equipment, and technological applications in biomedical research.

The workshop is part of IR Sant Pau’s commitment to promoting the continuous training of healthcare professionals and encouraging the integration of innovative technologies into medical practice. These learning spaces are essential for maintaining excellence in patient care and fostering the development of research in the field of robotic surgery. Moreover, this experience has allowed doctors to assess first-hand the advantages of robotic surgery in terms of precision, risk minimisation, and optimisation of surgical times.

Research has highlighted an indisputable fact: sex and gender identity directly influence health, well-being, and the progression of diseases. So much so that today, no research or healthcare activity can be considered complete without an authentic gender perspective.

At the Institut de Recerca Sant Pau (IR Sant Pau), we believe that research on women’s health and the incorporation of the sex and gender perspective in research projects should be an essential part of our center’s agenda.

On the occasion of International Women’s Day (8M) and in connection with the IR Sant Pau’s Transversal Health and Gender Program, we are introducing a new tool to guide our research staff in evaluating their research with a gender perspective: the Hipatia checklist.

From now on, the Ethics Committee for Research with Medicines (CEIm) will incorporate this checklist as an essential document when submitting a protocol for evaluation.

The CEIm is an independent body that, according to the legal provisions that accredit it, is tasked with ensuring the protection of the rights, safety, and well-being of the subjects involved in a trial, as well as providing a public guarantee of this protection by reviewing and approving the protocol, the investigator’s suitability, the facilities, and the materials and methods to be used in obtaining and documenting the informed consent of the subjects.

Consult the checklist here.

Why is it important to research with a gender perspective?

• Different health and disease patterns are known to vary according to sex and gender.
• Knowledge about the diagnosis, treatment, and prevention of diseases primarily comes from studies conducted on male cells, male mice, and men.
• Medicine and healthcare are based less on evidence generated from women than from men.

A collaborative study by the Centre for Biomedical Research Network (CIBER) at the Sant Pau Research Institute (IR Sant Pau) and the Institute of Biomedical Research of Barcelona (IIBB-CSIC) has identified a new therapeutic target for the treatment of abdominal aortic aneurysm (AAA), a degenerative vascular disease with high mortality and no effective pharmacological options.

The study, published in the journal Biomedicine & Pharmacotherapy, reveals how the enzyme ATP-citrate lyase (ACLY) contributes to the development of AAA. The findings show that inhibition of this enzyme with bempedoic acid—a drug used to lower high cholesterol—reduces inflammation and provides protection against the formation of abdominal aortic aneurysm in an experimental model.

The research was led by Dr Cristina Rodríguez Sinovas, head of the Cardiovascular Remodelling Regulatory Mechanisms research group at IR Sant Pau, and Dr José Martínez-González from IIBB-CSIC, both researchers in the Cardiovascular Diseases area of CIBER (CIBERCV).

AAA mainly affects men over the age of 65, with an estimated prevalence of between 4% and 8%. The prevalence in women is significantly lower (around 1% to 2%), but the risk of aortic rupture is higher, and they also have a worse prognosis following surgery.

This disease is characterised by exacerbated inflammation and destructive remodelling of the arterial wall. Currently, the only therapeutic option is surgical intervention in high-risk cases, highlighting the need for alternative strategies.

In this study, samples from AAA patients were analysed, and research was conducted on inflammatory cell cultures and a preclinical mouse model of the disease. “The results show the strong induction of the active form of ACLY in the inflammatory infiltrate of the human aneurysm and how the administration of bempedoic acid in an experimental mouse model improves survival, limits the disorganisation and rupture of elastic fibres in the vascular wall, and attenuates both local and systemic inflammatory responses,” explains Dr Rodríguez Sinovas, coordinator of the study.

“The study highlights the contribution of ACLY in AAA and suggests the potential of repurposing bempedoic acid for the management of these patients, while also laying the groundwork for future clinical trials to assess the potential benefits of this drug in AAA,” concludes Dr Lidia Puertas-Umbert, the study’s first author and a researcher at CIBER and IIBB-CSIC.

The study also involved the collaboration of CIBER research groups from the areas of Cardiovascular Diseases and the Pathophysiology of Obesity and Nutrition, based at the Vall d’Hebron Research Institute and the University of Barcelona.

Reference article:

Puertas-Umbert L, Alonso J, Blanco-Casoliva L, Almendra-Pegueros R, Camacho M, Rodríguez-Sinovas A, Galán M, Roglans N, Laguna JC, Martínez-González J, Rodríguez C. Inhibition of ATP-citrate lyase by bempedoic acid protects against abdominal aortic aneurysm formation in mice. Biomed Pharmacother 2025;184:117876. https://doi.org/10.1016/j.biopha.2025.117876.

The Sant Pau Research Institute (IR Sant Pau) and the Fundació Puigvert, a national and European reference centre in the diagnosis and treatment of rare renal and urogenital diseases, have participated in a decisive step in the management of Alport syndrome with the publication of the first multidisciplinary clinical guideline that integrates a systematic review of the literature, expert multidisciplinary experience, and patient associations.

This tool, recently published in Nephrology Dialysis Transplantation (ERA/Oxford Academic), addresses one of the most common hereditary kidney diseases within its low prevalence at the population level, characterised by haematuria (microscopic blood loss in urine), proteinuria and, in some cases, kidney failure and hearing and vision impairments.

The new guideline stems from the collaboration between experts in nephrology, genetics, ophthalmology, pathology, and otorhinolaryngology, based on an exhaustive bibliographic review combined with data from accumulated clinical experience in both paediatric and adult populations. It provides clear recommendations for monitoring and personalised treatment, integrating patients’ real experiences and needs through the involvement of their associations.

Alport syndrome affects both children and adults and is caused by the presence of abnormal collagen at the renal level. It presents in two forms, depending on its hereditary pattern.

• The X-linked variant mainly impacts males, whereas the autosomal recessive form modifies both boys and girls, presenting hearing problems and ocular alterations.
• The autosomal dominant form, diagnosed mostly in adults, does not involve hearing or visual impairment and has significantly lower severity in terms of renal involvement. It is the most common form.

Molecular Genetics, a Key Factor

Recently, thanks to advances in genetic diagnosis, we have been able to more accurately identify patients with the dominant variant of Alport syndrome (COL4A3, COL4A4).

Dr Roser Torra Balcells, a nephrologist, expert in Hereditary Kidney Diseases (HKD), Coordinator of Rare Diseases at the Fundació Puigvert, and researcher in the Nephrology group at the Sant Pau Research Institute (IR Sant Pau), has led the development of the clinical guidelines, hosting international experts at the Fundació Puigvert for the consensus meeting. Her expertise has been decisive in consolidating a comprehensive approach that allows for early diagnosis and the best treatment.

Dr Mònica Furlano, also a researcher in the Rare Diseases group at the Fundació Puigvert and in the Nephrology group at IR Sant Pau, highlights: “With this guideline, we aim to improve diagnosis and treatment, as well as open new lines of research to identify the factors involved in disease progression, which we still do not fully understand and need to investigate further.”

Another relevant aspect of this guideline is that it emphasises the essential role of a multidisciplinary approach, integrating various disciplines with the close collaboration of patient associations to ensure that recommendations are practical and adapted to clinical reality. Furthermore, strategies are proposed to avoid unnecessary treatments—such as the indiscriminate use of immunosuppressants—and to minimise exposure to nephrotoxic drugs, thereby ensuring better renal survival and, ultimately, a better quality of life.

With this contribution, the Fundació Puigvert reaffirms its commitment to innovation and excellence in the management of hereditary kidney diseases, consolidating its position as a pioneering centre in integrating research and clinical practice. The publication of this multidisciplinary guideline marks a milestone, as Dr Roser Torra explains: “It is the first comprehensive clinical guideline on Alport syndrome, a condition that is increasingly being diagnosed in our country.”

Reference article:

Torra R, Lipska-Ziętkiewicz B, Acke F, Antignac C, Becker JU, Cornec-Le Gall E, van Eerde AM, Feltgen N, Ferrari R, Gale DP, Gross O, Haeberle S, Wlodkowski T, Heidet L, Lennon R, Massella L, Topaloglu R, Pfau K, Del Prado Venegas Pizarro M, Zealey H, ERKNet, ERA Genes&Kidney and ESPN WG Hereditary Kidney Disorders groups. Diagnosis, management and treatment of the Alport syndrome – 2024 guideline on behalf of ERKNet, ERA and ESPN. Nephrol Dial Transplant 2024. https://doi.org/10.1093/ndt/gfae265.

On Rare Disease Day, the Sant Pau Research Institute (IR Sant Pau) reaffirms the significance of scientific and clinical advancements in improving the diagnosis and treatment of these little-known conditions.

Rare diseases affect a relatively small number of people compared to more common illnesses, yet they have a profound impact on patients and their families. There are an estimated 7,000 rare diseases, around 80% of which are of genetic origin. Despite their low individual prevalence, they collectively affect millions worldwide. In Catalonia alone, approximately 350,000 people are thought to be living with a rare disease.

A Leading Centre for Biomedical Research in Rare Diseases

IR Sant Pau has established itself as a leading research centre in this field, thanks to the work of its Cross-disciplinary Programme in Genomic Medicine and Rare Diseases. With over 310 researchers and technicians working across 18 research groups, the programme has published more than 2,000 scientific papers and reviews since 2018, cementing Sant Pau’s position as a key player in this area.

Furthermore, Sant Pau is the Spanish institution with the strongest representation in the CIBERER (Spain’s Networked Centre for Biomedical Research on Rare Diseases), with five research groups funded by the Carlos III Health Institute (ISCIII). This involvement highlights Sant Pau’s role as a leading institution in translational research, bridging the gap between laboratory discoveries and clinical practice.

Precision Medicine: Paving the Way for a Promising Future

IR Sant Pau is deeply committed to personalised and precision medicine, a field that tailors treatments to the individual genetic profile of patients. The institute is actively involved in the IMPaCT project (Infrastructure for Precision Medicine Associated with Science and Technology), leading two major initiatives:

• IMPaCT-Genomics, led by Dr Jordi Surrallés, which aims to integrate genomics into the healthcare system to enhance the diagnosis and treatment of rare diseases.
• IMPaCT-Data, under the leadership of Dr José Manuel Soria, focusing on the management and large-scale analysis of medical data to advance research and improve clinical decision-making.

Additionally, Sant Pau is at the helm of four in-house projects in personalised medicine and collaborates extensively with other institutions, reinforcing its commitment to biomedical innovation.

Breakthroughs in Rare Disease Research

Lately, IR Sant Pau has made significant advances in the study and treatment of various rare diseases, pioneering new therapeutic approaches. One notable breakthrough is the demonstration of non-pharmacological therapies, such as cognitive rehabilitation and music therapy, in patients with Huntington’s disease, leading to cognitive improvement and delayed neurological deterioration.

Another study has identified the immune system’s key role in the progression of motor neurone disease (ALS), potentially paving the way for earlier diagnosis and new therapeutic strategies. Meanwhile, the institute is leading the SPAiN project, which seeks to improve the treatment of autoimmune neuropathies in Spain, ensuring fairer access to care.

A further achievement is the development of a new scale to assess the progression of cerebral small vessel disease linked to the NOTCH3 gene, which will facilitate earlier diagnosis and the design of targeted treatments.

These developments are just a few examples of the groundbreaking research being carried out at IR Sant Pau, which remains dedicated to translating scientific discoveries into tangible solutions that improve the lives of those affected by rare diseases.

As Rare Disease Day is observed worldwide, it serves as a crucial reminder of the efforts made by patients, researchers, and healthcare professionals who, day after day, strive to improve our understanding and treatment of these conditions.

During 2025, Condis Supermarkets is dedicating its Charity Rounding Up initiative to eight health-related research projects. One of these will be the Sant Pau Research Institute (IR Sant Pau), focused on women’s cardiovascular health. This campaign is already active in the supermarkets of the chain and will run until April 13th.

Women’s cardiovascular health is a crucial issue, and unfortunately, it is often poorly understood. According to the World Health Organization (WHO), cardiovascular diseases (CVD) are the leading cause of death among women worldwide, surpassing even cancer, accounting for 35% of female deaths.

Key figures:

• Approximately 8.6 million women die each year from cardiovascular diseases.
• Women are more likely to exhibit atypical symptoms of heart attacks, which can make early diagnosis difficult.
• The incidence of cardiovascular diseases can significantly increase after menopause, due to the decline in estrogen levels.

The biomedical research on women’s cardiovascular health conducted by IR Sant Pau is essential to improve diagnosis, tailor treatments, and identify risk factors.

Thanks to the donations raised, we will be able to:

• Conduct research on the causes and symptoms of CVD in women.
• Organize awareness campaigns about the importance of cardiovascular health.
• Launch training programs for healthcare professionals to improve diagnosis and treatment of cardiovascular diseases in women.

To continue this vital research, we need your support. Donations are essential to fund studies, clinical trials, and education and awareness programs on women’s cardiovascular health.

You can make your donation at Condis Supermarkets or through this website.

Dr Jordi Surrallés, Director of Sant Pau Research Institute (IR Sant Pau), has been recognised by the College of Biologists of Catalonia for his outstanding career and contributions to biology and biomedical research. This annual award honours professionals who have made significant contributions to scientific knowledge and its application in society.

This distinction is part of the Biologist’s Day Awards, an initiative launched by the College of Biologists of Catalonia in 2017. Held annually on 25 April, the event pays tribute to professionals in the field of biology. The date marks the anniversary of the publication of the DNA structure by James Watson and Francis Crick in 1953, a landmark moment in biological history. The awards acknowledge individuals or institutions that have significantly enhanced the prestige of the profession, either through their scientific achievements or their service to the field of biology.

The College’s Governing Board granted this award to Dr Surrallés in recognition of his ongoing research into the mechanisms that maintain genome stability and protect against disease, cancer, and ageing. He was also commended for his ability to translate this knowledge into innovative therapeutic and diagnostic strategies in oncology, precision medicine, and rare diseases, such as Fanconi anaemia.

Dr Surrallés graduated in Biological Sciences from the Autonomous University of Barcelona (1990) and obtained his PhD in Genetics (1994). He then expanded his postdoctoral experience in the Netherlands and Finland before establishing his own research team at the Autonomous University of Barcelona, where he serves as a Professor of Genetics. In 2017, he was appointed Head of the Genetics Service at Sant Pau Hospital and currently serves as Scientific Director of IR Sant Pau. He also leads research groups at both IR Sant Pau and the Centre for Biomedical Research in Rare Diseases (CIBERER). Since 2008, he has held the prestigious ICREA Academia recognition.

Throughout his career, Dr Surrallés has led over 60 competitive research projects funded by public and private institutions worldwide. He has also been involved in clinical trials, patents, and collaborations with biotechnology and pharmaceutical companies. In addition, he has delivered dozens of lectures at international conferences, published nearly 150 scientific articles, and supervised 20 doctoral theses.

Alongside Dr Jordi Surrallés, the College of Biologists of Catalonia has recognised seven other professionals in the 2025 Biologist’s Day Awards. Among them is Eloïsa Matheu de Cortada, an expert in animal acoustic communication and soundscapes, and founder of the Alosa record label. Another recipient is Dr Alfonso Valencia Herrera, a PhD in Biochemistry and Molecular Biology, an ICREA Research Professor, and Director of the Life Sciences Department at the Barcelona Supercomputing Centre.

In the field of environmental management, the award has been given to Ramon Jordana i de Simon, a graduate in Biological Sciences from the University of Barcelona and former Deputy Director-General for Hunting Activities and Inland Fisheries in the Catalan public administration. In the field of microbiology, Dr Jordi Barbé Garcia has been recognised. He is the Rector’s Commissioner at the Autonomous University of Barcelona for secondary education relations and is known for his significant contribution to teaching.

In the area of biomedical research, the College has awarded Dr Eduard Batlle Gómez, a researcher specialising in colorectal cancer and metastasis at the Institute for Research in Biomedicine (IRB Barcelona), for his studies on the relationship between intestinal stem cells and cancer development. In the field of bio-entrepreneurship, Salvador Garcia López, founder of “Sanitat Vegetal”, has been recognised for his work in integrated pest management in green spaces and gardening. Finally, science communicator Pere Estupinyà Giné has been honoured for his work in making biology and science accessible to the general public.

Through these awards, the College of Biologists of Catalonia highlights the contributions of these professionals across various areas of biology, from research and education to environmental management and science communication.

Dr Lorena Alba-Castellón, a researcher in the Oncogenesis and Antitumour Drugs research group at the Sant Pau Research Institute (IR Sant Pau) and affiliated with the Centre for Biomedical Research in Network – Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), has been awarded a €172,000 grant from the Spanish Association Against Cancer (AECC) in Barcelona as part of the 2024 call for applications. This funding will be allocated to the project Targeted and personalised nanomedicine as a therapeutic tool for patients with advanced-stage colorectal cancer, which falls under the Innova category. This category aims to identify projects that focus on the validation and commercial exploitation of research outcomes in the field of cancer.

The project aims to develop a new therapeutic tool based on nanoparticles specifically targeting the tumour microenvironment, a key factor in tumour resistance to conventional treatments. This microenvironment comprises non-tumour cells, such as fibroblasts, immune cells and blood vessels, which protect the tumour and contribute to its aggressiveness. Dr Alba-Castellón’s research has developed a nanoparticle capable of selectively eliminating pro-tumour fibroblasts, thereby reducing tumour size and modifying its environment to enhance an anti-tumour immune response.

“With this AECC grant, we will be able to advance the development of this innovative strategy by studying its effects on human samples from volunteer patients at Sant Pau Hospital. Moreover, we will confirm that, thanks to its specificity, it does not damage healthy tissues or cause systemic toxicity like other available therapies,” explains Dr Alba-Castellón.

The AECC 2025 Grant Award Ceremony took place on 24 February 2025 at the MGS auditorium in Barcelona. During the event, a total of 49 research grants were awarded in the province of Barcelona, with a total investment of €12 million. The aim of these grants is to promote innovative projects that contribute to exceeding a 70% cancer survival rate by 2030.

The event was also attended by prominent figures from the scientific and medical sectors, as well as institutional representatives, who highlighted the importance of research in advancing new treatments and improving the quality of life for cancer patients.

With this new grant, IR Sant Pau strengthens its position as a reference centre in biomedical research and innovation, reaffirming its commitment to translational research to improve the quality of life for cancer patients.

The prestigious Journal of Neurology has just published the results of a study carried out by researchers at the Sant Pau Research Institute (IR Sant Pau), demonstrating the benefits of cognitive rehabilitation and music therapy in patients with mild to moderate cognitive impairment associated with Huntington’s disease.

The study, conducted at the Clinical School of Neuropsychology and Language Pathology at Sant Pau Hospital, was led by Dr Andrea Moreu-Valls, Dr Arnau Puig-Davi, and Dr Saúl Martínez-Horta. The results confirm that these non-pharmacological interventions not only improve patients’ cognitive status but also promote structural and functional changes in the brain, delaying the progression of neurological deterioration.

According to Dr Jaime Kulisevsky, head of the Parkinson’s Disease and Movement Disorders Group at IR Sant Pau and director of the Parkinson’s and Movement Disorders Unit at Sant Pau Hospital, who coordinated the study, “this work demonstrates that cognitive intervention can not only improve patients’ functionality but also influence neuronal plasticity mechanisms, opening new therapeutic perspectives.”

Study Methodology

The clinical trial, lasting twenty-four weeks, included 44 participants with early or intermediate-stage Huntington’s disease. The patients were divided into three groups: one received cognitive training through the NeuronUP platform, another underwent active music therapy sessions, and a control group received no intervention. Each session lasted 45 minutes and was conducted weekly. Researchers assessed patients’ progress through neuropsychological evaluations, functional impact questionnaires, and neuroimaging studies.

The results showed a significant improvement in cognitive functions and a reduction in apathy in patients who participated in either of the two therapies. Changes were also observed in brain functional connectivity and the preservation of certain brain areas, suggesting a neuroprotective effect.

Impact on the Brain and Disease Progression

Dr Saúl Martínez-Horta, also a researcher in the Parkinson’s Disease and Movement Disorders Group at IR Sant Pau and a participant in the study, highlights the significance of the findings: “Thanks to magnetic resonance imaging techniques, we have been able to demonstrate that these interventions not only impact cognitive performance but also modify brain function and help preserve areas particularly affected by Huntington’s disease, such as the caudate and putamen.”

This finding is particularly relevant, as until now, there was no objective evidence demonstrating the direct influence of these types of interventions on preserving brain structure in Huntington’s patients. The study indicates that cognitive stimulation techniques may help reduce the loss of grey matter in key brain regions, potentially slowing disease progression.

Dr Arnau Puig, another researcher involved in the study, also emphasises the importance of patient motivation: “Apathy is one of the main challenges in Huntington’s disease. Many patients stop engaging in activities due to a lack of motivation, which worsens their quality of life. We have observed that participation in these therapies not only improves cognition but also helps them feel more active and engaged, which is very valuable for both patients and their families.”

Dr Kulisevsky adds: “We must bear in mind that this is a neurodegenerative disease with relatively rapid progression. The fact that we can observe positive changes suggests that deterioration could be less severe if this type of treatment were applied continuously.” He further states: “Moreover, these results make us reflect on the need to invest more efforts in these types of interventions. Traditionally, medicine has prioritised pharmacological treatments, but studies like this demonstrate that there are valid alternatives that can significantly improve patients’ quality of life.”

What is Huntington’s Disease?

Huntington’s disease is a hereditary neurodegenerative disorder caused by a mutation in the HTT gene, leading to progressive degeneration of neurons in certain brain areas, affecting motor control, cognition, and the emotional state of patients. The first symptoms usually appear between the ages of 30 and 50 and include involuntary movements, cognitive difficulties, and psychiatric disorders.

It is a rare disease, with an incidence of approximately 5 to 10 cases per 100,000 people. Currently, there is no cure, and its progressive course inevitably leads to a gradual loss of functional independence and quality of life.

Applications in Other Neurodegenerative Diseases

The researchers also emphasise that these strategies could be useful for other neurodegenerative diseases. “This is a clear example of translational research,” states Dr Kulisevsky. “Our findings suggest that these types of interventions should be integrated into the care offering for patients with neurodegenerative diseases, just as is done with physiotherapy or speech therapy.”

Dr Saúl Martínez-Horta highlights that these interventions could also be applied to diseases such as Parkinson’s or Alzheimer’s: “We know that neurodegeneration affects various brain areas and that neuronal plasticity can help maintain certain functions for longer. Our study suggests that, although they are not a cure, these therapies can help preserve patients’ quality of life for a longer time, delaying the loss of autonomy.”

In this regard, the researchers advocate for integrating these types of interventions into standard treatment protocols, as Dr Saúl Martínez-Horta emphasises: “This study shows us that non-pharmacological therapies have real potential and could become a standard component in the treatment of these diseases.”

Reference Article:

Moreu-Valls A, Puig-Davi A, Martinez-Horta S, Kulisevsky G, Sampedro F, Perez-Perez J, Horta-Barba A, Olmedo-Saura G, Pagonabarraga J, Kulisevsky J. A randomised clinical trial to evaluate the efficacy of cognitive rehabilitation and music therapy in mild cognitive impairment in Huntington’s disease. J Neurol 2025;272:202. https://doi.org/10.1007/s00415-025-12927-2

The Sant Pau Research Institute (IR Sant Pau) has been honoured in the research centre category at the second edition of the Transconca Awards 2025, an event that recognises the work of professionals, organisations and companies dedicated to rare diseases.

The award was given for research on CADASIL, a rare neurovascular disease of genetic origin. This recognition highlights IR Sant Pau’s contribution to scientific progress and improving the quality of life of those affected by this condition.

The awards ceremony took place on Sunday, 23 February, at the football ground in La Pobla de Claramunt, where professionals and organisations committed to rare diseases gathered. Dr Elena Muiño and Dr Jesús Martín, members of IR Sant Pau’s Pharmacogenomics and Neurovascular Genetics Research Group, accepted the award on behalf of the research team.

“We would like to thank this platform for allowing us to express our commitment to researching these diseases. This recognition is a great motivation to continue advancing CADASIL research. Initiatives like this set an example, and we hope even more people will join this cause next year,” said Dr Muiño during the event.

The Transconca Awards, organised by the entity of the same name, aim to raise awareness and support research and the work of professionals and families striving to improve the lives of people with rare diseases. For IR Sant Pau, this recognition serves as further motivation to continue investigating and advancing knowledge of these conditions.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a rare genetic disease that affects the brain’s blood vessels. It is caused by pathogenic genetic variants in the NOTCH3 gene and leads to alterations in cerebral blood flow, resulting in ischaemic strokes, migraine with aura, cognitive decline and, in advanced stages, dementia. There is currently no curative treatment, but ongoing research is essential to better understanding the disease and developing new therapeutic strategies.

A team of researchers from the Sant Pau Research Institute (IR Sant Pau) has published a study in the Journal of Neuroinflammation that, for the first time, examines in depth the role of the peripheral immune system in amyotrophic lateral sclerosis (ALS) at the single-cell level. Their findings suggest that immune system cells—particularly two subpopulations of Natural Killer (NK) cells—may play a crucial part in the development and progression of this neurodegenerative disease.

ALS is a condition that causes the progressive degeneration of motor neurones, leading to a loss of muscle function and, eventually, affecting vital functions such as breathing. At present, there is still no curative treatment or sufficiently effective therapy to halt its progression, and the estimated average survival after diagnosis is between 3 and 5 years.

First detailed analysis of the immune system in ALS

Although the role of the immune system had already been demonstrated in diseases such as Alzheimer’s, until now, there had not been a similarly in-depth study confirming this significance for ALS. “It was suspected that there could be an immunological component involved in the disease, but it had not been demonstrated in depth at the cellular level,” explains Dr Oriol Dols, a researcher in the Neurobiology of Dementias group and Memory Unit at IR Sant Pau, who coordinated the study.

To address this challenge, 14 patients with sporadic ALS—i.e. with no known genetic mutations explaining the condition (around 90% of ALS cases)—were recruited and their immune profile compared with that of 14 healthy individuals who served as a control group.

Using single-cell RNA sequencing—a technique that allows researchers to analyse gene expression in individual cells—the scientists were able to study over 100,000 immune cells from peripheral blood one by one, detecting highly specific cellular and genetic alterations in each subpopulation of lymphocytes, monocytes and, notably, NK cells.

Altered NK cell subpopulations

NK cells are primarily known for their role in defending against viral infections or tumour cells. However, this study showed an abnormal increase in certain subpopulations of NK cells in ALS patients, which also presented a hyperactivated state.

“The key finding is that not only are NK cells increased overall, but there are two very specific subpopulations with different implications,” notes Dr Dols. One of these subpopulations appears to exert a modulator effect on other immune cells, such as CD8 or CD4 T lymphocytes; the other is closely associated with neurodegenerative processes, as evidenced by a connection with neurofilament levels, a marker of neuronal damage. “This suggests that these NK cells might directly influence motor neurone injury,” adds the specialist.

Changes also in monocytes and T lymphocytes

In addition to NK cells, the study reveals alterations in subpopulations of monocytes and CD8 T lymphocytes with an increased capacity for antigen presentation. Altogether, this indicates a global immune system imbalance that may contribute to a neuroinflammatory environment and speed up the death of motor neurones.

“Knowing that the peripheral immune system is involved in ALS opens up new lines of inquiry: from the search for blood biomarkers to facilitate earlier diagnosis, to prospective therapies targeting these specific subpopulations,” says Esther Álvarez-Sánchez, also a researcher in the Neurobiology of Dementias group and Memory Unit at IR Sant Pau, and first author of the article.

At present, there is no approved drug that specifically modulates NK cells or T lymphocytes in the context of ALS, so these findings represent an initial step towards developing more targeted and combined treatments.

Next steps and impact

This study was carried out with the largest cohort so far analysed by single-cell RNA sequencing in ALS (14 patients and 14 controls). The statistical outcomes confirm the robustness of the immune differences detected, and the team is already conducting a longitudinal follow-up of the same patients one year later to gauge how the immune profile evolves.

Likewise, in vitro experiments are being designed to combine patients’ NK cells with motor neurones, to decipher which specific signals trigger the hyperactivation of these subpopulations and how they relate to neuronal death. “Understanding the mechanism that drives part of the immune system to become ‘uncontrolled’ is essential, and we must also explore how to modulate it without impairing the beneficial functions of these cells,” explains Dr Dols.

Although this work does not immediately translate into a treatment, the identification of key immune subpopulations in ALS is a promising step forward. “Just as in cancer we have learned to regulate the immune response to combat tumours, in ALS we are moving towards the idea of combining therapies addressing both neurodegeneration and the altered immune response,” concludes Dr Dols.

Reference article:

Álvarez-Sánchez E, Carbayo Á, Valle-Tamayo N, Muñoz L, Aumatell J, Torres S, Rubio-Guerra S, García-Castro J, Selma-González J, Alcolea D, Turon-Sans J, Lleó A, Illán-Gala I, Fortea J, Rojas-García R, Dols-Icardo O. Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis. J Neuroinflammation 2025;22:15. https://doi.org/10.1186/s12974-025-03347-0.

As part of the celebration of the International Day of Women and Girls in Science, on Sunday, 9th February, more than 2,500 people enjoyed the Women and Girls in Science Festival, an event organised by the Sant Pau Research Institute (IR Sant Pau) to bring science closer to everyone and to encourage scientific vocations among girls and young people. The Panoramic Area of Tibidabo Amusement Park was transformed into a large open-air laboratory, where researchers shared their passion with the public through experiments, workshops, and interactive activities.

A day full of experiments and science

With more than 20 workshops and educational activities, involving over 60 professionals and volunteers from Sant Pau, families had the opportunity to enjoy a unique day, combining learning with fun.

• Scientific experiments in action: from extracting DNA from fruit to viewing cells and tissues under a microscope, children were able to experience science up close.
• 3D models of the human body: three-dimensional representations of organs helped to better understand their functions.
• Healthy habits in motion: physical skill circuits, reflex tests, and nutrition workshops highlighted the importance of physical activity and a balanced diet.
• Talks on mental and sexual health: designed for young people, these sessions provided practical tools for maintaining emotional and physical well-being.
• Meetings with female researchers: professionals from Sant Pau shared their experiences, inspiring many young girls to see themselves as future scientists.

Dr Jordi Surrallés, Director of IR Sant Pau, highlighted the significance of such initiatives: “At IR Sant Pau, we celebrate this event as an opportunity to recognise and promote female talent in all areas of research, convinced that a diversity of perspectives enriches science and drives innovation.”

He also emphasised the need to ensure equal opportunities for all female researchers. “It is essential to actively encourage girls and young women to participate in scientific projects and to provide an inclusive and diverse environment that fosters significant progress in public health.”

The Mariona Project

The “Mariona Researcher” project is an educational and outreach initiative developed by IR Sant Pau. Mariona is a character who represents an eight-year-old girl passionate about science and medicine, whose mission is to inspire children and young people to explore the world of scientific research. At this age, many girls tend to lose interest in science, partly due to persisting stereotypes and a lack of female role models—an issue that this project aims to address.

The project also highlights the role of women in science, showcasing real-life examples of female researchers who share their professional and personal experiences to promote gender equality in the field.

Science with a gender perspective

At IR Sant Pau, a continuous dialogue with society is fostered, aligned with its Responsible Research and Innovation (RRI) plan and its goals for Scientific Education and Public Engagement. As a CERCA centre and an accredited Unit of Scientific Culture and Innovation (UCC+i) by FECYT, its commitment to bringing research closer to the public is unwavering. As the only research institute in Catalonia with a transversal gender research programme, IR Sant Pau is at the forefront of the latest scientific advancements and highlights the importance of gender-sensitive research and the role of women in the future of science.

Meanwhile, Tibidabo Amusement Park, known for its dedication to educational and social projects, collaborates with various organisations to promote socially impactful initiatives. In this context, the park provided an ideal setting to showcase the work of IR Sant Pau to families.

Several companies also participated in the celebration of the Women and Girls in Science Festival. Casio, through its Women Do Science project, designed special edition calculators featuring Mariona, which were distributed to children wearing wristbands from other events. Additionally, Grupo Julià facilitated the event’s logistics, while Ametller Origen Fundació, 4M, MODIband Projectes Culturals, Technovation Girls Catalonia, Funky Fun Crew, and DiR supported the organisation of various activities, making this an inspiring and unforgettable day.

A new multicentre study reveals why the structure of the ApoB100 protein, present in LDL together with so-called “bad cholesterol”, plays a crucial role in the propensity of LDL to accumulate in the arterial walls of patients with familial hypercholesterolaemia, thus promoting the formation of atherosclerotic plaque.

The work is co-led by the researcher from the Institute for Biomedical Research of Barcelona (IIBB-CSIC) and CIBERCV, Vicenta Llorente Cortes, and the researcher from the University Toulouse Paul Sabatier, Valerie Samouillan.

Familial hypercholesterolaemia is a relatively common genetic disorder. It affects approximately one in every 200 or 300 people. Those affected have had high levels of low-density cholesterol (LDL) since birth and, consequently, a higher risk of cardiovascular disease and increased rates of premature death from this cause.

Why do LDL particles clump together more in this congenital disease? Are there biochemical and physical differences that explain it? That is what they have tried to clarify in this study, published in the Journal of Lipid Research.

The work involved 10 research centres in Spain and France. Among them, and in addition to the IIBB-CSIC and CIBER, are the Institute of Materials Science of Barcelona (ICMAB-CSIC), the Sant Pau Research Institute (IR Sant Pau), the Autonomous University of Barcelona (UAB), the CIRIMAT Institute (Toulouse, France) and the Miguel Servet Hospital in Zaragoza.

Structure of ApoB100: less flexible in small, dense LDL of patients with familial hypercholesterolaemia

LDL particles in patients with familial hypercholesterolaemia show a greater tendency to aggregate and form plaques. This is due, explains Vicenta Llorente Cortes, “to the fact that the ApoB100 protein in LDL has a particular structural conformation, with a high percentage of rigid alpha helices [secondary structures], compared to the LDL of healthy patients.”

Based on samples from 35 patients with familial hypercholesterolaemia and 29 healthy individuals as a control group, the researchers have demonstrated that in patients with familial hypercholesterolaemia, the protein present in LDL is smaller due to its high esterified cholesterol content and has less structural flexibility compared to the LDL of healthy individuals. As a result, these LDL exhibit a reduced ability to recover their structure in the arterial intima, favouring their accumulation in the inner wall of the arteries.

Various techniques to study LDL particles

Among other things, the study measured how easily LDL particles clump together using dynamic light scattering techniques, as well as the size, composition and structure of LDL particles by electron microscopy.

As Llorente explains, one of the most impactful findings was detecting the difference in the percentage of flexible secondary structures in the ApoB100 of patients with FH, which would not have been possible without the collaboration of the biophysics group led by Dr Samouillan (University of Toulouse). This group applied FTIR infrared spectroscopy to determine the structure of the protein and, in particular, to quantify the content of stable alpha helices and flexible alpha helices in the LDL of the control groups and patients.

The results suggest that developing strategies to structurally preserve ApoB100, and in particular the percentage of flexible alpha helices in LDL, could be a new way to reduce the risk of heart disease in these patients.

This finding provides a new perspective for understanding how alterations in the structure of ApoB100 can directly influence the risk of developing cardiovascular diseases. It also opens up possibilities for designing specific therapies aimed at modulating the flexible alpha helix content in LDL, helping to prevent atherosclerosis.

“In our research group,” adds Vicenta Llorente, “we are comparing whether PCSK9 inhibitors [a type of drug] can help preserve the percentage of flexible alpha helices and whether these effects are comparable with those achieved through innovative peptide tools developed in our group specifically for this purpose. With these new peptide tools, we aim to preserve the structural flexibility of the ApoB100 protein in the LDL of patients with familial hypercholesterolaemia.”

Reference article:

Maria Teresa La Chica Lhoëst, Andrea Martínez, Eduardo Garcia, Jany Dandurand, Anna Polishchuk, Aleyda Benitez-Amaro, Ana Cenarro, Fernando Civeira, Amable Bernabé, David Vilades, Joan Carles Escolà-Gil, Valerie Samouillan, Vicenta Llorente-Cortes. ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients. Journal of Lipid Research. https://pubmed.ncbi.nlm.nih.gov/39557294/