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/

The Sant Pau Research Institute (IR Sant Pau) will lead the innovative SPAiN project (Spanish Partnership for Autoimmune Neuropathies), a national initiative aimed at transforming the knowledge and care of autoimmune neuropathies (ANs), a group of rare diseases affecting the peripheral nervous system.

For its development, the project has been awarded €1,634,710.00 through the “PMPER-24 – Research Projects on Rare Diseases” call by the Carlos III Health Institute, as part of the Joint Missions of the Ministry of Health and the Ministry of Science, Innovation and Universities. A total of €20 million has been allocated to rare disease research projects, resulting in the approval of eight research projects across Spain, two of which are based in Catalonia: the IR Sant Pau project and another led by the Germans Trias i Pujol Research Institute (IGTP). This last project aims to create a national network to tackle the challenges of type 1 myotonic dystrophy, in collaboration with the INCLIVA Health Research Institute at the University Clinical Hospital of Valencia.

Under the leadership of Dr Luis Querol, researcher of the Neuromuscular Diseases Group at IR Sant Pau and neurologist at the Neuromuscular Unit of the Neurology Department at Sant Pau. The IR Sant Pau plays a central role in this national network. It brings together 17 reference centres across 9 autonomous communities. This leadership reflects the institute’s excellence as a neuromuscular reference centre in Spain and its commitment to translational research.

ANs, a group of rare diseases affecting the peripheral nervous system, pose a significant medical challenge due to their difficult diagnosis and the limitations of current treatments. These conditions include Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy. Although treatable, these diseases present diagnostic and therapeutic challenges that can compromise patients’ quality of life.

“These diseases pose numerous challenges. Their causes remain largely unknown, diagnosis is difficult, and while therapeutic options exist, they are limited and urgently need updating. SPAiN was created with the aim of transforming our understanding of these conditions and improving the lives of those affected,” explains Dr Querol.

The project will leverage cutting-edge technologies such as genomics, proteomics, and antigenomics to identify more precise biomarkers and explore new therapeutic pathways. These tools will enable personalised treatments and improved patient monitoring, thereby reducing the impact of these diseases on patients’ lives.

A direct impact on healthcare

One of SPAiN’s key pillars is ensuring that scientific advancements reach patients equitably across the entire country. Thanks to the network led by IR Sant Pau, any patient, regardless of their location, will be able to benefit from the expertise and resources of the country’s leading reference centres.

“Autoimmune neuropathies impact a small but dispersed population, making the creation of a national network crucial. At Sant Pau, we have worked to ensure that SPAiN reaches every corner of Spain, providing more equitable care and opportunities for patients to participate in cutting-edge research,” emphasises Dr Querol.

IR Sant Pau’s role as a national and international leader

IR Sant Pau’s leadership in this project is built on its long-standing role as a reference centre for autoimmune neuropathies. For years, the institute has been involved in international networks such as IGOS (International Guillain-Barré Syndrome Outcome Study) and INCBase (International CIDP Database). Now, by coordinating SPAiN, it seeks to drive advancements that will establish Spain as a global reference in this field.

“This project is a unique opportunity to showcase the expertise accumulated at Sant Pau and to expand our impact through a national network that is also connected to major international consortia. This demonstrates our institute’s commitment to scientific excellence and to improving patients’ lives,” states Dr Querol.

An investment in the future of personalised medicine

SPAiN will not only lay the foundations for new therapies and better diagnostics, but it will also enhance our understanding of the mechanisms behind these rare diseases. The project will run over the next two years, making use of existing resources and expanding the research and healthcare network.

“Although autoimmune neuropathies are rare diseases, their consequences can be devastating. SPAiN aims to break down barriers, creating tools that not only enhance diagnosis but also enable the development of more effective and accessible treatments,” concludes Dr Querol.

The Hypatia Mars association presented, on 28 January at the Modernist Building of Hospital Sant Pau, the second mission of female researchers of different ages and disciplines, which will take place from 2 to 15 February at the Mars Research Desert Station (MDRS) in the Utah desert, United States. During this mission, a new crew of analogue astronauts will live in isolation conditions, coinciding with the International Day of Women and Girls in Science, celebrated on 11 February. The project will once again have the collaboration of the Sant Pau Research Institute (IR Sant Pau) and Hospital Sant Pau, both of which already participated in the first mission.

What is the Hypatia II Project?

The Hypatia II project encompasses a series of initiatives aimed at exploring and overcoming the challenges posed by space exploration in terms of health, well-being, and sustainability from a female perspective. Within this framework, a project focused on menstrual health stands out, led by Dr Marina Martínez, a postdoctoral researcher in the Department of Geology at the Autonomous University of Barcelona (UAB), supported by a Margarita Salas grant. She is also a member of the Center for Advanced Sample Analysis of Astromaterials from the Moon and Beyond (Chip Shearer, PI) at SSERVI (NASA). In this project, she will collaborate with Dr Joaquim Calaf and Dr Josep Perelló, researchers from the Reproductive Health Group at IR Sant Pau and the Gynaecology and Obstetrics Service at Hospital Sant Pau.

This project addresses an often-overlooked issue: how to manage menstrual cyclicity during space missions, especially long-duration ones, such as the colonisation of the Moon or Mars. Currently, the suppression of the menstrual cycle through hormonal methods is a common practice among astronauts. However, this solution can lead to gender inequalities and negative implications for the female body.

Objectives of the Menstrual Health Project

The project is structured around three main areas of action aimed at integrating the perspective of female cyclicity in space exploration.

First, it seeks to make the female hormonal cycle visible and respected by incorporating this knowledge into the organisation of space missions. This includes adapting tasks, work rhythms, and environmental conditions to the specific needs of each phase of the crew members’ cycles.

Second, the project prioritises research and the implementation of sustainable solutions for menstrual management. Among these solutions, the use of the menstrual cup, developed in collaboration with AstroCup, stands out as an alternative that helps reduce waste, improve hygiene, and ensure greater comfort in microgravity environments.

Finally, the project explores the potential of menstrual blood as fertiliser through experiments with plants grown in space conditions. The goal is to assess its viability as a useful resource within an efficient recycling system aligned with the zero-waste principle.

An Initiative Within a Global Programme

This project is just one of the multiple research lines being developed within the Hypatia II programme, a multidisciplinary initiative that promotes a more inclusive, sustainable, and innovative approach to space exploration. The knowledge gained from these investigations will not only benefit space missions but also have direct applications on Earth in areas such as health, sustainability, and gender equality.

A study recently published by researchers from the Sant Pau Research Institute (IR Sant Pau) and the Stroke Unit of Sant Pau Hospital in Journal of Lipid Research provides new evidence on the essential role of the qualitative properties of lipoproteins, such as LDL and HDL, in the pathophysiology of cardiovascular diseases, including ischaemic stroke. The findings underscore the importance of going beyond traditional quantitative cholesterol levels to evaluate the risk of these pathologies.

Dr Sonia Benítez, a researcher in the Cardiovascular Biochemistry Research Group at IR Sant Pau and one of the study’s authors, emphasised that “it is not so much the amount of LDL or HDL as their quality that determines the residual risk of ischaemic stroke. This study confirms that some qualitative alterations in lipoproteins, such as the increased negative electric charge in LDL and HDL (LDL(-) or HDL(-)), could play a causal role in the progression of cardiovascular diseases.”

The relationship between ischaemic stroke and lipoproteins

Ischaemic stroke, one of the leading causes of mortality and disability worldwide, is often linked to carotid atherosclerosis. Approximately 20% of strokes are directly associated with the presence of atheromatous plaques in the carotid arteries, significantly increasing the risk of severe vascular events. Traditionally, the clinical management of these patients has focused on reducing LDL and HDL cholesterol levels. However, this new study from IR Sant Pau highlights that the qualitative characteristics of lipoproteins are also crucial in the development and progression of these diseases. This new perspective creates opportunities to innovatively address lipoprotein alterations and associated risks.

The study was conducted as an observational cohort study at Sant Pau Hospital between January 2016 and March 2019. The population studied included adult patients who had experienced anterior circulation ischaemic stroke and recently diagnosed carotid atherosclerosis, as well as a control group of healthy subjects. Lipoproteins were isolated from blood samples of 27 healthy subjects and 64 patients with carotid atherosclerosis seven days and one year after the stroke.

Alterations in qualitative properties

Seven days after the first stroke, LDL showed an increase in negative charge, an elevation of pro-inflammatory ceramides and triacylglycerols, and a decrease in phospholipids and cholesterol. A comprehensive lipidomic study of LDL was conducted in collaboration with Dr Öörni’s group at the Wihuri Research Institute in Helsinki. These LDL modifications are associated with inflammatory and atherogenic processes that increase the vulnerability of carotid plaques. Regarding HDL, protein composition alterations were identified, such as a reduction in apoA-I levels and an increase in apoA-II and apoC-III, impairing their antioxidant and anti-inflammatory properties and compromising their ability to prevent LDL modification and its inflammatory effect.

A notable aspect is that these qualitative alterations persist despite the early introduction of medications like statins. “This suggests that these modifications are deeply rooted in the patient’s pathophysiology. However, one year after the stroke, thanks to therapeutic interventions such as statins and antiplatelet agents, as well as possible lifestyle improvements, lipoproteins showed significant improvement,” adds Dr Sonia Benítez.

Thus, LDL became less prone to oxidation and aggregation, while HDL partially recovered its protective properties. Additionally, a reduction in LDL(-) and HDL(-) levels—electronegative lipoprotein subtypes with high atherogenic potential—was observed. “This may mean that therapeutic interventions can partially reverse the harmful effects of these alterations,” adds Dr Núria Puig, also a researcher in the Cardiovascular Biochemistry Group and the first author of the publication.

A paradigm shift

This research introduces a paradigm shift in understanding the functional role of lipoproteins in cardiovascular diseases, particularly in ischaemic stroke associated with carotid atherosclerosis. The findings underscore the need for an integrative approach to explore the qualitative properties of lipoproteins to identify patients at high risk of complications, even when their quantitative lipid levels appear normal.

This can help personalise treatments based on the specific characteristics of each patient and better tailor pharmacological and non-pharmacological interventions. The researchers also point towards developing therapeutic strategies aimed at modifying lipoprotein composition, with a potential positive impact on preventing cardiovascular complications. This includes reducing LDL(-) and HDL(-) through dietary changes, physical exercise, and more consistent adherence to statin treatments.

Clinical implications and future directions

However, the study has some limitations, such as the small sample size, which makes it difficult to generalise the results. This highlights the need for studies with larger cohorts to confirm the findings and analyse specific subgroups, such as by sex or type of therapeutic intervention. In this regard, Dr Pol Camps from the Stroke Unit, second author of the publication, and Dr Benítez have recently formed, along with other European groups, a consortium called BioStroke focused on stroke biomarker research, aiming to establish collaborations that will allow for expanding studies to larger patient cohorts.

According to Dr Benítez, “translational research in this field is key to bringing these findings into clinical practice. Our future goal is to develop tools to identify patients at higher risk and eventually design therapeutic strategies aimed at reversing these lipoprotein alterations.” This research opens a promising avenue for future clinical approaches that focus not only on traditional lipid levels but also on the qualitative properties of lipoproteins, thereby complementing current therapeutic strategies and reducing the risk of stroke recurrence and other cardiovascular complications.

Reference article:

Puig, N., Camps-Renom, P., Hermansson, M., Aguilera-Simón, A., Marín, R., Bautista, O., … Benitez, S. (2024). Alterations in LDL and HDL after an ischemic stroke associated with carotid atherosclerosis are reversed after 1 year. Journal of Lipid Research, (100739), 100739. doi:10.1016/j.jlr.2024.100739

The Sant Pau Research Institute (IR Sant Pau) has been selected to coordinate the ambitious European project Synapsing, an unprecedented initiative funded with seven million euros by the European Union through the Horizon-Europe programme. This project, involving thirteen leading institutions in clinical research, neuroimaging, and social sciences from nine European countries, aims to revolutionise the diagnosis and management of psychiatric and neurodegenerative diseases through blood biomarkers, socioeconomic data, and innovative tools.

The coordination of the project will fall to Dr Olivia Belbin, head of the Molecular Neurodegeneration Group at IR Sant Pau, who will bring her expertise in translational research to advance understanding of neurodegenerative diseases. Dr Maria J. Portella, head of the Mental Health Research Group, will also play a key role, contributing her specialised knowledge in mental health to ensure effective integration between both fields of study. This joint leadership reinforces the multidisciplinary and collaborative character of the project, highlighting the synergy between two traditionally separate areas of research.

Synapsing not only promises scientific advances but also seeks to promote greater equity in medical care. By integrating knowledge from different disciplines and geographical areas, the project aims to create a diagnostic and therapeutic model applicable across Europe. “IR Sant Pau is coordinating, for the first time, a European project of this scale, marking a historic event in our trajectory and consolidating our position as a reference centre in clinical and translational research,” highlighted Dr Belbin.

Unprecedented Innovation

In the field of mental health and neurodegenerative research, the lack of objective diagnostic tools and personalised treatments remains a significant challenge. Synapsing represents a paradigm shift, seeking practical and scientific solutions to these problems.

“Psychiatric disorders, such as schizophrenia, major depressive disorder, and bipolar disorder, often share symptoms with neurodegenerative diseases like Alzheimer’s and Parkinson’s. This overlap causes delays in diagnoses and complicates the administration of appropriate treatments,” explained Dr Portella, who added that this new European project will attempt to address this issue through an innovative approach based on biomarkers and transdiagnostic data.

Among Synapsing’s primary objectives is the integration of advanced technologies, multimodal data, and biological samples from patients with psychiatric and neurodegenerative diseases into unified and easily accessible collections. This will overcome the lack of transdiagnostic research resources and establish the foundations for a better understanding, diagnosis, and measurement of psychiatric symptoms.

The project will also seek to understand the shared pathophysiological mechanisms of synaptic degeneration that lead to clinical symptoms common to both types of disorders. This knowledge will guide the development of more effective and specific therapeutic strategies. “Another key aspect is the development of blood biomarkers to improve diagnosis. Synapsing seeks to establish tools that allow for faster and more objective diagnoses of disorders such as major depressive disorder, bipolar disorder, and schizophrenia, reducing errors and confusion with neurodegenerative diseases,” commented Dr Belbin.

Additionally, the project aims to better manage patients with psychiatric symptoms through biomarkers that enable the measurement of treatment efficacy and the prediction of therapeutic outcomes. “This will help personalise therapies and ensure more rigorous monitoring of patient progress,” added Dr Portella.

Analysing Sociodemographic Risk Factors

Another fundamental pillar is the analysis of modifiable sociodemographic risk factors that may be associated with biological changes in patients with psychiatric and neurodegenerative diseases. The findings from this research will provide evidence for designing public policies aimed at preventing the debilitating symptoms of these diseases.

Finally, Synapsing focuses on engaging the research community, clinicians, and patients in a collective effort to bridge the gap between research, clinical practice, and governmental policies. This objective aims to ensure that scientific advances translate into tangible benefits for patients and society.

A Collaborative and Multidisciplinary Approach

Synapsing will bring together experts from various disciplines, including neurology, psychiatry, biology, social sciences, and ethics. This approach is essential to addressing the complexity of these diseases, which are often studied separately but share underlying mechanisms. As Dr Belbin commented, “For the first time, a project of this magnitude addresses both psychiatric disorders and neurodegenerative diseases, recognising their overlaps and leveraging a transdisciplinary approach to better understand these pathologies.”

IR Sant Pau will play a central role in all phases of the project thanks to collaboration between its Memory Unit and its Mental Health Unit. As Dr Portella highlighted, “This collaboration marks a turning point in integrating the efforts of two traditionally separate areas. It is an example of how breaking down barriers between disciplines can generate significant advances in patient care.” This synergy is expected to enable the integration of clinical, neurobiological, and sociodemographic data for a more in-depth understanding of these conditions.

Creation of a Large Cohort

One of the main innovations will also be the generation of an unprecedented cohort, including more than 3,000 patients from various European countries, encompassing both psychiatric and neurodegenerative diseases. By unifying clinical, neurobiological, and sociodemographic information in a single database, the project aims to provide a unique tool for future research.

The cohort will not only allow for the identification of blood biomarkers distinguishing these pathologies but will also facilitate the analysis of sociodemographic risk factors. “For the first time, we will have a database integrating multidimensional information from patients across the psychiatric and neurodegenerative spectrum. This will be crucial for understanding the connections between these diseases and how they evolve in different contexts,” said Dr Belbin.

Furthermore, this joint effort establishes a new way of addressing challenges in mental health and neurodegenerative research. The quality and scale of this data will help outline more effective clinical guidelines and design personalised treatments, opening new doors in translational medicine. “This integrated and accessible database will have a lasting impact, allowing researchers and clinicians across Europe to advance together towards more equitable and personalised medicine,” emphasised Dr Portella.

Expected Results

The Synapsing project will span five years, aiming to achieve significant advances in the diagnosis, treatment, and prevention of psychiatric and neurodegenerative diseases. Among the most anticipated results is the identification of key blood biomarkers in 2025, marking a historic milestone for personalised medicine. Additionally, the first scientific articles reflecting the impact of this project on understanding these complex diseases are expected to be published in 2026.

Beyond scientific advances, the project seeks to transform the clinical and social approach to these conditions. The collected data will be used to update clinical guidelines, enabling more precise diagnoses and treatments tailored to the specific needs of each patient. Similarly, evidence-based recommendations will be developed for public policies aimed at mitigating the risk factors associated with these diseases.

The social focus of Synapsing is also essential. Through a specially designed questionnaire, sociodemographic factors influencing the progression and development of these diseases will be identified. “This project not only seeks biomedical results but also aims to improve patients’ living conditions by understanding how factors such as unemployment or socioeconomic inequality affect their health,” pointed out Dr Belbin. These findings will enable governments to implement more effective preventive measures and reduce inequalities in healthcare.

L’Institut de Recerca Sant Pau (IR Sant Pau) ha estat beneficiat amb una ajuda d’1.406.625 euros per part de l’Institut de Salut Carlos III de Madrid (ISCIII). Aquest suport econòmic es destinarà a modernitzar i millorar la Unitat d’Investigació Clínica del centre, reforçant la seva capacitat per dur a terme estudis d’alta qualitat i donar resposta a les necessitats dels pacients. L’ajuda s’emmarca en un projecte de l’ISCIII per impulsar la investigació a Espanya, tant mitjançant la millora de les unitats ja existents com amb la creació de noves.

En el cas de l’IR Sant Pau, els fons permetran optimitzar els espais i adquirir equipaments d’última generació, amb especial atenció a les tecnologies informàtiques i la telemedicina. Aquestes millores beneficiaran especialment els pacients amb patologies neurodegeneratives i malalties complexes, consolidant l’IR Sant Pau com un referent en recerca biomèdica.

“Aquesta ajuda ens brinda l’oportunitat de fer un salt qualitatiu en les nostres capacitats de recerca. A l’IR Sant Pau estem compromesos a oferir als nostres pacients els tractaments més innovadors, i aquesta millora ens permet avançar en aquesta direcció”, va explicar la Dra. Rosa Antonijoan, directora de Farmacologia Clínica del Centre d’Investigació del Medicament de l’IR Sant Pau i responsable del projecte.

“Volem ser un referent en assaigs clínics per a pacients fràgils, especialment aquells amb patologies neurodegeneratives. Aquesta inversió ens permetrà garantir que els nostres pacients tinguin accés a investigacions capdavanteres en un entorn segur i adequat”, va afegir la Dra. Antonijoan.

Adaptació a les noves necessitats dels pacients

La unitat d’investigació clínica de l’IR Sant Pau ja compta amb una trajectòria consolidada, però aquest projecte potenciarà les capacitats del centre per tal d’adaptar una zona amplia per pacients amb dificultat d’accés a instal·lacions i garantir l’atenció del pacient fràgil en un entorn controlat i proper al personal clínic. Aquesta zona inicialment estava dissenyada per a la participació de pacients sans. “La recerca en neurociències i els assaigs oncològics de fase 1 són àrees prioritàries per a l’IR Sant Pau, però els pacients que hi participen són fràgils i necessiten cures especials que ara, amb l’ampliació, esperem poder oferir de manera més adequada”, va apuntar la Dra. Antonijoan.

Entre les principals millores hi ha la redistribució dels espais per maximitzar l’ús de les instal·lacions i atendre un major nombre de pacients. Es preveu ampliar l’espai disponible per a la investigació clínica a la planta 1 de l’institut, passant dels 1.371,12 m² actuals als 1.612,10 m². La reforma inclourà l’accessibilitat plena per als participants, amb zones de circulació àmplies, sales d’espera confortables, espais que garanteixin la privacitat i una senyalització clara. També es treballarà per millorar el benestar dels acompanyants, humanitzant l’entorn.

Una part de l’ajuda es destinarà a l’adquisició d’equipaments avançats, amb la incorporació de tecnologies de telemedicina i sistemes informàtics per gestionar els assaigs. Es busca implementar un model de recerca clínica descentralitzada, amb l’objectiu d’incrementar la participació de col·lectius vulnerables en els estudis, incloent-hi persones grans, amb malalties neurològiques o minoritàries.

També està prevista l’adequació de les instal·lacions per garantir la comoditat i seguretat dels pacients amb malalties com Alzheimer, Parkinson, Huntington o ELA. Aquestes adaptacions ampliaran la capacitat dels investigadors per dur a terme estudis més complexos i ambiciosos, incrementant l’impacte dels resultats tant en la comunitat científica com en l’atenció als pacients.

Impuls als assaigs clínics en fases inicials

Un dels objectius principals del projecte és enfortir els assaigs clínics en fases 1B i 2, àrees on l’IR Sant Pau ja ha demostrat un gran potencial. Aquestes fases són essencials per avaluar la seguretat i els primers indicis d’eficàcia dels tractaments. A més, es contempla la possibilitat d’integrar assaigs de fase 3 quan sigui necessari, posicionant l’IR Sant Pau com a líder en recerca translacional.

S’espera augmentar tant el nombre de pacients que participen en els assaigs com la qualitat i humanitat de la seva experiència. Les mesures proposades fomentaran l’equitat i la justícia en la distribució de la recerca, alhora que afavoriran el reclutament i la permanència dels pacients en els estudis. Així, la unitat es consolidarà com un pol d’atracció per a la recerca clínica pública i privada, amb especial atenció als pacients fràgils, en particular aquells amb malalties neurològiques o rares. Tot això es farà minimitzant els desplaçaments, amb un impacte ambiental positiu gràcies a la reducció d’emissions de CO₂.

Interoperabilitat per sistemes informàtics

L’ajut també és destinarà a desenvolupar i implementar un model d’interoperabilitat per sistemes informàtics, cosa que resulta imprescindible per situar al pacient al centre de la informació sanitària. Aquest model permetrà la coordinació i l’accés eficient a la documentació clínica. Amb un sistema interoperable, els professionals de la salut podran accedir ràpidament a la informació rellevant, millorant així la presa de decisions clíniques i optimitzant l’atenció al pacient.

Aquest enfocament també facilitarà la integració de dades provinents de diverses fonts, amb la qual cosa es promourà una atenció més coordinada i efectiva i s’asseuran d’aquesta manera les bases per a una col·laboració en xarxa per a la realització d’assajos clínics descentralitzats i preparar la informació per a possibles usos secundaris en xarxa.

Calendari d’implementació

El desenvolupament del projecte està planificat per a un període de dos anys. Durant aquest temps, s’adquiriran els equipaments i es completaran les obres necessàries abans de finals de 2026. Per al 2027, l’IR Sant Pau espera tenir totes les millores plenament operatives, consolidant-se com un centre de referència en investigació clínica avançada.

A més, es proporcionarà formació especialitzada al personal del centre per garantir l’ús òptim dels nous recursos i tecnologies, assegurant una atenció de màxima qualitat als pacients que participin en els estudis.

As part of the annual meeting of the American Society of Haematology (ASH) 2024, one of the foremost global events in this field, Dr Ana Caballero, researcher in the Cellular Immunotherapy and Gene Therapy group at the Sant Pau Research Institute (IR Sant Pau) and associate in the Haematology Service led by Dr Javier Briones, delivered an oral presentation on the results of the phase I/II clinical trial of the HSP-CAR30 treatment for patients with refractory or relapsed Hodgkin lymphoma and CD30+ T-cell lymphoma. This innovative cellular therapy, a pioneering development in Europe, was entirely designed and manufactured at the IR Sant Pau and Hospital. It has drawn significant interest due to its safety and efficacy in a patient population with unmet therapeutic needs.

To date, 32 patients have been treated with HSP-CAR30, and plans are in place to enrol an additional 10 patients to further bolster the findings. According to Dr Caballero, this expansion will help confirm the robustness of the preliminary results and establish a firmer basis for the treatment’s future development. The results presented indicate that 55% of patients treated with HSP-CAR30 achieved complete remission of the disease—an impressive figure considering the severity of the studied population. Additionally, it was estimated that 41% of patients would remain progression-free two years post-treatment, an encouraging indicator of the therapy’s potential to provide long-term cancer control.

Dr Ana Caballero highlighted the significance of these results: “What is most encouraging is that the responses are not only effective but also durable, representing a genuine advance for a population with very limited options,” she explained.

An innovative treatment developed entirely at Sant Pau

The HSP-CAR30 treatment is based on genetically modified CAR T-cell technology, designed to specifically recognise and attack the CD30 antigen present in tumour cells. “We designed a treatment combining a second-generation CAR T-cell with an enriched population of memory T-cells, optimised to deliver a potent and long-lasting response,” explained Dr Laura Escribá, coordinator of CAR T-cell production and quality control within the Cellular Immunotherapy group of the Haematology Service. She added, “The results we are seeing are promising and reflect the team’s effort to offer a solution to patients who have no other therapeutic options.”

A safe and long-lasting drug

One of the most notable features of HSP-CAR30 is its manageable safety profile. During the trial, side effects such as cytokine release syndrome were mostly mild and controllable with available treatments. The incidence of neurotoxicity was minimal, underscoring the therapy’s potential as not only effective but also a safe option. “Our goal was always not just to develop a treatment that works, but also one that is tolerable for patients. We know that quality of life is just as important as survival,” Dr Caballero emphasised.

The initial results also demonstrate significant persistence of the therapeutic effect. According to the data presented, the modified CAR T-cells remain active in the patient’s body for up to 24 months post-infusion, reinforcing their ability to offer lasting tumour control. Dr Caballero explained that the focus on memory T-cells is key to extending the treatment’s benefits: “Our product is designed to last and to continue combating cancer over time. This is particularly important for patients facing aggressive and refractory tumours.”

Commitment to research

Hodgkin lymphoma (HL) is known for its high cure rate in the early stages of treatment. However, up to 30% of patients experience recurrence or fail to respond to initial therapies, leaving them in a critical situation with few alternatives. In her presentation at ASH, Dr Caballero stressed the importance of addressing this unmet need: “Hodgkin lymphoma, although treatable in most cases, presents a major challenge when patients fail to respond to conventional treatments. It is precisely in this population that HSP-CAR30 is showing its transformative potential.”

The ASH Congress, recognised as the leading international forum in haematology, was the ideal platform to showcase the potential impact of HSP-CAR30. The presentation generated widespread interest among specialists and experts, who emphasised the importance of further advancing these innovative therapies. Dr Caballero underlined the urgency of continuing research and development of the treatment: “Although the results are encouraging, we know there is still work to be done. These preliminary data are a significant step, but we remain committed to validating and improving this treatment for future patients.”

The development of HSP-CAR30 exemplifies Sant Pau’s leadership in advanced immunotherapy. This project demonstrates how interdisciplinary collaboration and academic research can have a direct and meaningful impact on patients’ lives. “We are proud of what we have achieved so far, but our ultimate goal is for treatments like HSP-CAR30 to become an accessible therapeutic option for patients facing this type of cancer,” concluded Dr Caballero.

Researchers from the Neurobiology of Dementia group at the Sant Pau Research Institute (IR Sant Pau) have published two pioneering studies in the journals Alzheimer’s & Dementia and Neurology, revealing key advances in understanding Alzheimer’s disease in individuals with Down syndrome (DS). They have demonstrated the relationship between white matter hyperintensities and cerebral microhemorrhages with the development of this disease in this population.

Studies in individuals with DS are crucial because this population has a highly determined genetic risk for developing Alzheimer’s due to the triplication of chromosome 21. This genetic condition leads to the overproduction of beta-amyloid, one of the primary biological characteristics of the disease. As a result, almost all individuals with DS show biological signs of this condition from the age of forty, although clinical symptoms may appear later.

This phenomenon makes DS a unique model for studying the early mechanisms of Alzheimer’s disease and its interactions with cerebrovascular factors, providing data that may also be applicable to the general population. “The life expectancy of individuals with DS has significantly increased in recent decades, but this success has highlighted the need to address the growing impact of Alzheimer’s in this population,” says Dr. Alexander Bejanin, researcher in the Neurobiology of Dementia group at IR Sant Pau, who coordinated the two studies now published. “Our studies allow us to identify key factors that could improve early detection and prognosis of the disease, not only in individuals with DS but also in the general population.”

White matter hyperintensities

White matter hyperintensities (WMHs) are detected through magnetic resonance imaging (MRI) as bright areas in the brain. In individuals with DS, these lesions appear earlier and with greater severity than in the general population. They are key indicators of cerebrovascular issues and are strongly linked to the progression of Alzheimer’s disease.

According to Alejandra Morcillo-Nieto, the lead author of the study published in Alzheimer’s & Dementia, “WMHs are crucial for understanding how cerebrovascular disease and Alzheimer’s disease are related in individuals with DS. These lesions are particularly prevalent in periventricular, frontal, parietal, and occipital regions, and this is the first study to identify the areas where they are most common in this population.”

The study, which analysed 261 adults with DS and 131 adults without this condition, shows that “WMHs increase with age and are correlated with biomarkers such as beta-amyloid and phosphorylated tau, suggesting a direct connection with the pathophysiology of Alzheimer’s disease, independent of vascular risks,” says Morcillo-Nieto. Moreover, these anomalies are related to clinical status, suggesting that they may be directly influencing functional deterioration.

Cerebral microhemorrhages

Cerebral microhemorrhages are small deposits of blood in the brain that may indicate vascular damage and are associated with Alzheimer’s disease. In individuals with DS, these lesions are more frequent and primarily concentrate in the posterior regions of the brain, such as the cerebellum and occipital areas. This is one of the findings of the study published in Neurology, and although they are not exactly the same areas as those for WMHs, they are strongly related.

According to Sàra Zsadanyi, the lead author of the study, “microhemorrhages are a key piece of understanding the risk of complications in anti-amyloid therapies. Their increasing prevalence with age allows us to better identify key moments for intervention.” The study identified microhemorrhages in 20% of individuals with DS, compared to only 8.9% in healthy controls.

These lesions increase not only with age but also with clinical severity, rising from 12% in early stages to 35% in advanced stages of dementia. The results also show a correlation with Alzheimer’s disease biomarkers, highlighting their relevance for monitoring and treating this vulnerable population.

Overall assessment of advances

According to Dr. Alexander Bejanin, “with our studies, we want to highlight the crucial role of characterising these two vascular lesions in the development of new therapies for Alzheimer’s disease.” Dr. Bejanin also emphasises that the findings “are not only relevant for Down syndrome but have broader implications for understanding Alzheimer’s disease in general.”

These discoveries have a direct impact on the management and treatment of the disease. “With the arrival of new anti-amyloid therapies, these lesions are a crucial factor to consider, as they may increase the risk of adverse effects,” warns Dr. Bejanin. This underscores the importance of using MRI to monitor disease progression and personalise treatments.

Future perspectives

The research also opens the door to exploring new preventive and therapeutic strategies. According to Dr. Bejanin, “studies in DS allow us to better understand the relationship between vascular lesions and Alzheimer’s pathology, offering a unique opportunity to apply this knowledge to the general population.” The researchers highlight that these findings could improve understanding of the role of vascular lesions in Alzheimer’s, both as a cause and a consequence of the disease.

Sant Pau Hospital is an international reference centre for neurodegenerative diseases associated with DS. Its Alzheimer-Down Unit, the only one in Spain, continues to lead research redefining the future of diagnosis and treatment for these conditions. This unit works in a multidisciplinary way, combining clinical and translational research with a personalised approach to meet the specific needs of individuals with DS.

Reference articles:

• Morcillo-Nieto AO, Zsadanyi SE, Arriola-Infante JE, (…) Bejanin A. Characterization of white matter hyperintensities in Down Syndrome. Alzheimer’s Dement. 2024; 1-15. https://doi.org/10.1002/alz.14146
• Zsadanyi SE, Morcillo-Nieto AO, R. Aranha M, (…), Bejanin A. Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome. Neurology 2024; 103:e209676. https://doi.org/10.1212/WNL.00000000002096

Researchers from the Sant Pau Research Institute (IR Sant Pau) have collaborated with an international team to develop a tool that promises to transform how small vessel disease associated with the NOTCH3 gene is assessed and managed, including CADASIL, the most severe presentation of this condition. Published in the prestigious journal JAMA Neurology, the study introduces a staging scale that classifies the progression of this disease into five main stages and nine subgroups, offering for the first time a clear model to understand its evolution.

Dr Israel Fernández-Cadenas, head of the Pharmacogenomics and Neurovascular Genetics Group at IR Sant Pau and one of the researchers involved in developing this classification, explains that this advancement represents a fundamental shift in the management of these diseases. “Until now, it was known that CADASIL progressed over time, but physicians lacked tools to classify its progression systematically. The new scale, however, provides a framework that allows doctors to place patients in a specific stage, which not only helps provide them with a clearer understanding of their prognosis but also reduces the uncertainty that characterises many rare diseases like this one.”

Easy Application to Clinical Practice and Research

The scale has been designed to integrate data from magnetic resonance imaging (MRI) and functional assessments, tools already part of routine medical practice. According to Dr Elena Muiño, a researcher in Dr Fernández-Cadenas’ group and another contributor to the development of the classification, this means that its implementation will not require additional investments or complex technologies, a key factor for its adoption in diverse medical settings, including those with limited resources.

One of the major advantages of this tool is that it not only facilitates a better understanding of the disease’s progression but also improves the way experimental treatments are designed and evaluated. “By classifying patients according to the stage of the disease, clinical trials will be able to identify more precisely which therapies are effective for each stage,” explains Dr Muiño.

Application in Other Contexts

The impact of this scale is not limited to CADASIL. Although this study focused on patients with genetic variants associated with the NOTCH3 gene, the model could also be applied to other forms of small vessel disease, including sporadic forms such as those caused by hypertension. Dr Muiño emphasises that “CADASIL is considered the genetic model par excellence for small vessel disease. Therefore, it seems logical to think that this classification system will be applicable to other causes of small vessel disease, facilitating their study, which also lack a specific treatment.”

The development of the scale initially involved a cohort of 195 patients with CADASIL and was later validated in a sample of over 1,700 individuals from various regions worldwide, confirming its international applicability. Additionally, a longitudinal follow-up of up to 18 years allowed researchers to observe how the disease progresses in most patients, particularly over long periods. This knowledge not only helps set clearer expectations for patients and their families but also provides a solid foundation for designing more specific therapeutic interventions.

A Challenge that Still Remains

Despite these advances, Dr Muiño acknowledges that treating CADASIL remains a challenge. “Currently, there are no specific therapies for this disease beyond general measures to manage cardiovascular risk factors. However, implementing this scale represents an essential step towards developing targeted treatments.”

The publication of this study in a high-impact journal such as JAMA Neurology underscores its scientific and clinical significance, highlighting the importance of a multidisciplinary and international approach to tackling complex diseases like this. “This is a crucial step forward in shedding light on an area that, until now, was filled with uncertainty,” concludes Dr Muiño. “Not only are we giving patients a better understanding of what they face, but we are also laying the groundwork for future treatments that could change their lives.”

About CADASIL and the NOTCH3 Gene

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a genetic condition that affects the brain’s small blood vessels, causing an alteration in blood flow distribution to various brain regions. This condition is caused by genetic variants in the NOTCH3 gene, located on chromosome 19, whose alteration leads to the aggregation of the Notch3 protein and other proteins, ultimately resulting in damage to the blood vessel wall.

The progressive damage to these small vessels leads to clinical manifestations including recurrent strokes, migraines, mood disorders, and, in advanced stages, vascular dementia. Most cases typically manifest between the ages of 45 and 60, although earlier and later forms have been described depending on the location of the genetic variant and individual factors such as sex and cardiovascular risk factors.

Although CADASIL has historically been considered a rare disease, recent studies suggest its prevalence could be much higher than previously estimated. It is believed that up to 1 in 300 people carries a pathogenic genetic variant in the NOTCH3 gene. Indeed, many individuals may not develop severe symptoms or may present with milder forms of the disease depending on the location of the genetic variant. This observation has generated growing interest in research, as it could explain a significant proportion of undiagnosed cerebrovascular diseases, particularly in older adults.

Reference Article:

Gravesteijn G, Rutten JW, Cerfontaine MN, Hack RJ, Liao Y-C, Jolly AA, et al. Disease severity staging system for NOTCH3-associated small vessel disease, including CADASIL. JAMA Neurol [Internet]. 2024; Disponible en: http://dx.doi.org/10.1001/jamaneurol.2024.4487