This past weekend, the Born Centre for Culture and Memory was the venue for the 18th Science Festival, a large gathering for all audiences to engage with science and knowledge. The Sant Pau Research Institute was one of the participating entities, offering three workshops that captivated numerous families.

On Saturday afternoon, visitors were able to enjoy a dynamic and educational activity to find out what the brain, heart and blood look like and how they work through life-size 3D models and interactive posters. Children had to connect the parts of the organs and identify their functions in order to better understand these three fundamental pillars of the human body. The activity, led by Jorge Clusa, outreach coordinator at the Sant Pau Research Institute, was very popular among children.

On Sunday morning, Marta Cano and Romina Miranda, researchers from the mental health group at the Sant Pau Research Institute, also invited the youngsters to explore the structures of the brain and its functions by assembling a 3D paper puzzle of this organ. The attendees also had a lot of fun participating in an original brain bingo game in which each move revealed a curiosity about the human brain.

To close the Festival, on Sunday afternoon, Dr. Robert Belvís, Dr. Noemí Morollón, Dr. Juan Aibar, professionals of the Headache and Neuralgia Unit of the Hospital de Sant Pau, with the support of Iago Andreu, a clinical engineer from the hospital’s Dimension Lab, explored the complexity of neurosurgery. The attendees who joined us discovered how technology helps to plan operations with more precision and safety, and were able to live an immersive experience by trying on virtual reality glasses.

The Sant Pau Research Institute thanks everyone who made this success possible, both the organizers and the participants, who contributed to making this Science Festival a memorable edition.

Researchers at the Sant Pau Research Institute (IR Sant Pau) have published a study in Epilepsy & Behavior documenting a high frequency of neuropsychiatric symptoms in adults with tuberous sclerosis complex (TSC), a rare, multisystem genetic disorder with highly variable clinical expression. While the condition primarily affects the nervous system, it can also impact other organs such as the kidneys, heart, skin, and lungs.

The study provides an in-depth analysis of the cognitive and emotional profiles of 28 adult patients with confirmed TSC and no severe intellectual disability, highlighting an unmet clinical need. Although most participants exhibited significant emotional, cognitive, or behavioral alterations, only a minority had received specialized mental health care.

The most common symptoms included mood swings (reported in 80% of cases), excessive shyness (70%), and sleep and attention disorders (60%). Additionally, half of the patients reported low self-esteem. Despite this symptom burden, only four individuals—14% of the sample—had received psychiatric or psychological care. “Our patients have many problems in these neuropsychiatric domains, but they don’t seek help for them. And unfortunately, we don’t have the resources to monitor them more closely either because there are so many gaps in mental health care that this ends up being an unmet need,” explains Dr. Alba Sierra, researcher in the Epilepsy Group at IR Sant Pau, neurologist at Hospital Sant Pau, and corresponding author of the study.

Genetic Origin and Variable Manifestations

TSC is caused by mutations in the TSC1 or TSC2 genes, which lead to abnormal activation of the mTOR pathway and the formation of hamartomas—benign masses made up of normal but disorganized cells. These can develop in different organs. When they affect the central nervous system, they may cause epilepsy, intellectual disability, and neuropsychiatric disorders.

While the impact of epilepsy in TSC has been widely studied, emotional and cognitive symptoms—collectively known as TAND (TSC-Associated Neuropsychiatric Disorders)—have received less attention, especially in adults. “Disease severity is highly variable: some people have mild symptoms and are diagnosed by chance in adulthood, while others experience severe epilepsy, intellectual disability, and multi-organ involvement. That’s why we included a wide age range, from 18 to 65 years. This disease can manifest at any point in life,” notes Dr. Sierra.

Comprehensive Clinical and Neuropsychological Assessment

The study combined a clinical evaluation with an extensive neuropsychological battery. All patients underwent standardized intelligence testing (WAIS-IV) and cognitive screening (MoCA), along with specific scales to assess anxiety, depression, quality of life, and subjective health perception. The researchers also used the TAND-L checklist to detect symptoms across different domains, from behavior to academic skills. Clinically, the study considered epilepsy history, infantile spasms, findings from MRI and EEG, and genetic profile when available.

Beyond Epilepsy: Factors Linked to Greater Impact

Results showed a clear link between epilepsy severity and duration and poorer cognitive performance. Significant associations were also observed with other clinical factors. For example, patients with a history of infantile spasms or mutations in the TSC2 gene had more impaired cognitive profiles and greater emotional and academic difficulties. Additionally, the presence of hamartomas in the frontal and parietal lobes was associated with behavioral, learning, and other specific cognitive impairments.

“We found that epilepsy isn’t the only factor driving these symptoms. Genetics and the location of brain hamartomas also play a role. The impact is multifactorial,” emphasizes Dr. Sierra.

Cross-Specialty Coordination: A Structural Need

Beyond the clinical findings, the study encourages reflection on the current care model for TSC patients. Traditionally, neurology appointments have focused on controlling epileptic seizures, without systematically addressing neuropsychiatric symptoms. “We tend to focus heavily on purely neurological symptoms, and perhaps haven’t explored these other issues—ones that directly affect quality of life—as much. This study draws attention to the need to look beyond the seizures,” adds Dr. Sierra.

In line with this more holistic perspective, the team underscores the need for multidisciplinary care. TSC doesn’t just impact the brain—it can lead to serious complications in vital organs, including kidney failure, cardiac issues, or lung disease. “Follow-up has to be comprehensive. A systemically involved disease like this requires joint work among specialists. It’s the only way to ensure high-quality care,” concludes Dr. Sierra.

Future Outlook: Toward Longitudinal Follow-Up

The study opens the door to future research aimed at tracking the progression of these symptoms over time. Longitudinal studies could provide more in-depth insight into how neuropsychiatric alterations evolve with age and help develop more effective, personalized intervention strategies.

Reference Article:

Toscano-Prat C, García-Sánchez C, Ros-Castelló V, Barguilla-Arribas A, Saladich IG, Rodríguez-Clifford K, Torra-Balcells R, Boronat S, Sierra-Marcos A. Cognitive and neuro-psychiatric profile in adult patients with epilepsy secondary to Tuberous Sclerosis Complex. Epilepsy Behav. 2025;166:110380. https://doi.org/10.1016/j.yebeh.2025.110380

The Sant Pau Research Institute and The Hospital de Sant Pau, who have once again participated together in the BCN Salut Games— the solidarity olympics of the health and research sector— have been crowned champions of this year’s edition, which gathered a total of 5,435 participants from 51 different centers.

More than 400 professionals from Hospital de Sant Pau took part in this sports event, where Sant Pau finished in first place, followed by Hospital Clínic and Sant Joan de Déu, in second and third place respectively.

The aim of this solidarity olympics is to encourage physical activity and healthy habits in the healthcare field, while also fostering cohesion, togetherness, and motivation within institutions and among participating organizations.

In addition, Sant Pau raised a total of €2,597 this year in solidarity donations from participating professionals. These funds will go to the Kàlida Foundation, a support center for people affected by cancer, offering care and guidance to individuals going through or having gone through cancer, as well as to their close circle of family, caregivers, and friends.

Soon, the BCN Salut Games organization will present Sant Pau’s management team with the trophy recognizing them as champions of the 2025 edition. The Kàlida Foundation will also receive the solidarity check with the funds raised, handed over by Sant Pau’s management.

An international study involving researchers from the Sant Pau Research Institute (IR Sant Pau) has demonstrated that women who are carriers of genetic mutations causing frontotemporal dementia (FTD) show a greater capacity to compensate for brain damage than men, at least in the early stages of the disease. The discovery suggests that sex is a key biological factor in the evolution of this hereditary form of dementia and opens the door to more gender-sensitive precision medicine.

The article was published in the journal Alzheimer’s & Dementia, the official publication of the Alzheimer’s Association, and is part of a series of three scientific papers on sex differences in the clinical and biological manifestations of genetic FTD. The research is part of the North American ALLFTD consortium and included collaboration from leading neuroscience and neuroimaging centers in San Francisco (UCSF) and Toronto (University of Toronto).

“What we observed is that, for the same degree of brain damage, women with FTD performed better than men in executive function and social cognition tests. This indicates they have greater cognitive and behavioral reserve,” explains Dr. Jesús García Castro, neurologist and researcher in the team led by Dr. Ignacio Illán-Gala at the Sant Pau Memory Unit and Sant Pau Research Institute (IR Sant Pau), and first author of the study.

FTD is a neurodegenerative disease still not well known to the general public, but which has gained recent attention following the diagnosis of actor Bruce Willis. Unlike Alzheimer’s, which primarily affects memory, FTD presents as personality changes, social behavior disturbances, and language or speech difficulties. It typically begins at an earlier age—between 45 and 65 years—and may lead to a progressive loss of executive functions such as judgment, empathy, or impulse control. For this reason, the study of behavioral changes is key to early detection.

A longitudinal look at brain resilience

Frontotemporal dementia is a rare neurodegenerative disease that usually appears between 45 and 65 years of age and severely affects personality, social behavior, and language. In about 30% of cases, it is caused by mutations in genes such as C9orf72, GRN, or MAPT, which lead to abnormal protein accumulation and progressive loss of brain tissue, especially in the frontal and temporal lobes.

Thanks to the systematic follow-up of the ALLFTD consortium, the researchers were able to analyze over 670 brain MRIs and clinical data from 394 carriers of pathogenic mutations and 279 non-carrier relatives over several years. They studied both asymptomatic individuals (presymptomatic phase) and those already diagnosed with mild cognitive impairment or dementia.

“This longitudinal design allowed us to observe how the disease evolves even before the first symptoms appear. And this is where we saw the female advantage: women showed better cognitive performance despite having greater degrees of frontal brain atrophy,” highlights Dr. García Castro.

The team used an innovative methodology known as the residual approach, which quantifies cognitive reserve: the discrepancy between a person’s actual performance and what would be expected based on their degree of neurodegeneration. This approach revealed that women, especially those carrying the C9orf72 expansion, maintained better executive and social functioning despite cortical thinning.

An advantage that fades with disease progression

Statistical models also showed that this female advantage is not permanent. As the disease progresses and brain damage extends, compensatory capacity decreases, and deterioration trajectories equalize between men and women in advanced stages.

“It’s as if the female brain has more capacity to resist the disease for a time, but once a certain threshold is reached, the decline accelerates,” summarizes Dr. García Castro. “This matches what has been observed in Alzheimer’s: greater initial resilience in women, followed by faster deterioration when symptoms emerge.”

Indeed, the study observed a trend towards later symptom onset in women (up to 6.5 years on average), although this result did not reach statistical significance due to sample size.

Clinical implications and future research directions

The work has important implications for the design of clinical trials and progression prediction models in hereditary dementias. Until now, most studies had not considered sex as a differentiating variable, which may have obscured important patterns in treatment response or clinical evolution.

“Our findings reinforce the need to integrate sex and gender perspectives into precision medicine, especially in diseases like FTD, where variability is enormous even within the same genetic mutation,” notes Dr. García Castro.

The Sant Pau group, in collaboration with international partners of the ALLFTD consortium, continues to analyze other modulators of progression in genetic FTD, including immunological, hormonal, and structural markers.

Study funding

The research was conducted as part of the North American ALLFTD (Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects) consortium, funded by the U.S. National Institute on Aging (NIA) and the U.S. National Institute of Neurological Disorders and Stroke (NINDS).

In addition, the work was supported by the Carlos III Health Institute through multiple projects (PI20/01473, PI23/01786, PI18/00435, PI20/01330, PI21/01395, PI21/00791, CP20/00038, PI22/00307, INT21/00073, CM21/00243 and CM23/00176), co-financed by the European Union. It also received funding from the Biomedical Research Network Centre on Neurodegenerative Diseases (CIBERNED) and the European Regional Development Fund (ERDF) under the slogan “A way to make Europe”.

At the international level, the study was supported by the Alzheimer’s Association (grants AARG-22-923680, AARF-22-924456 and GBHI ALZ UK-21-720973), the Alzheimer Society (UK), and the Global Brain Health Institute (GBHI). It also received support from the Tatiana Pérez de Guzmán el Bueno Foundation, and from the Horizon 2020 programme of the European Union.

In Catalonia, the research was promoted by the Department of Health of the Generalitat through the Strategic Plan for Health Research and Innovation (PERIS), and was supported by clinical talent contracts such as Juan Rodés and Río Hortega.

This institutional support has made it possible to carry out a large-scale multicenter study with participation from 18 centers in the United States and Canada, and consolidates Sant Pau’s leadership in advancing precision medicine in the field of neurodegenerative diseases.

Reference article:

Garcia Castro J, Rubio-Guerra S, Casaletto KB, Selma González J, Memel M, Vaqué-Alcázar L, Morcillo-Nieto A, Arriola-Infante J, Dols-Icardo O, Bejanin A, Belbin O, Fortea J, Alcolea D, Carmona-Iragui M, Barroeta I, Santos-Santos M, Sánchez Saudinós MB, Sala Matavera I, Heuer HW, Forsberg LK, Kantarci K, Staffaroni AM, Tartaglia C, Rankin KP, Boeve B, Boxer A, Rosen HJ, Lleó A, Illán-Gala I, ALLFTD Consortium. Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia. Alzheimers Dement 2025;21:e70070. https://doi.org/10.1002/alz.70070

A team of researchers from the Sant Pau Research Institute (IR Sant Pau) has received the 2025 Best Communication Award from the Catalan Resuscitation Council (Consell Català de Ressuscitació, CCR), in recognition of the scientific and translational impact of their work.

The winning study, titled “Region-Specific Vulnerability to Brain Damage Following Cardiac Arrest and Cardiopulmonary Resuscitation: Preclinical Studies in Pigs,” was led by Dr. Gemma Vilahur, head of the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Research Group at IR Sant Pau and a member of CIBERCV.

The research offers a comprehensive and holistic understanding of the pathophysiological mechanisms that occur in the brain following a five-minute cardiac arrest and subsequent resuscitation. Using a preclinical model, the study analyzes markers related to glial activation, apoptosis, and the deregulation of cellular survival pathways. It reveals a differential neuronal response across brain regions, with more intense inflammatory reactions and greater vulnerability to neuronal loss in the cerebral cortex, caudate nucleus, and hippocampus. While further exploration of these findings is underway, the results may have important implications for the development and implementation of targeted neuroprotective strategies in patients who have suffered cardiac arrest.

The award was presented on Tuesday, May 20, during the closing ceremony for the awards and grants hosted by the Academy of Medical Sciences of Catalonia in Barcelona. Representing the team, María Ángeles Cánovas—who has been involved in the research project since its inception—accepted the award.

This recognition highlights the scientific excellence of the work being conducted at IR Sant Pau, particularly in the field of cardiovascular research and its connection to brain health. It also underscores the importance of cross-disciplinary and cross-institutional collaboration in advancing the understanding of complex conditions such as those resulting from cardiac arrest. The study involved researchers from Hospital Clínic de Barcelona, the Liverpool Centre for Cardiovascular Science (United Kingdom), and CIBERCV (Carlos III Health Institute).

Researchers from the Sant Pau Research Institute (IR Sant Pau) and CIBER-BBN have led an exhaustive scientific review of therapies aimed at the CXCR4 receptor, a key target in more than 20 types of cancer. The article, published in Biomarker Research, provides a comprehensive overview of the most advanced therapeutic and diagnostic approaches under development to act on this receptor, considered a poor-prognosis biomarker and a characteristic signature of tumor stem cells.

The CXCR4 receptor (C-X-C chemokine receptor type 4) is a membrane protein belonging to the family of G-protein-coupled receptors whose normal role is to guide cell migration, especially in the immune system and during embryonic development. Under physiological conditions it regulates processes such as hematopoiesis, tissue regeneration, and the inflammatory response, acting as a cellular docking site for its natural ligand, the chemokine CXCL12. However, this essential function becomes corrupted in pathological contexts such as cancer, where CXCR4 overexpression in tumor cells gives them advantages such as the ability to invade tissues, evade the immune system, and resist treatments.

Beyond its physiological role, CXCR4 has for decades been an object of interest in HIV research because the virus uses it as a co-receptor to enter certain immune cells. This intense work in the context of HIV infection made it possible to characterize its structure, develop multiple antagonists, and deepen our understanding of its activation mechanisms—knowledge that is now being repurposed in oncology.

“The CXCR4 receptor has proved to be an extraordinary molecular target for precision oncology. Its overexpression in many tumor types makes it a strategic target both for blocking cancer progression and for accurately delivering drugs to the most aggressive tumor cells,” emphasizes Dr. Ugutz Unzueta, researcher in the Oncogenesis and Antitumor Drugs group and coordinator of the review.

The IR Sant Pau group has been at the forefront of this line of research for the past fifteen years, with more than one hundred publications focused on developing nanomedicine based on protein nanoparticles that selectively recognize and attack CXCR4⁺ cells. Their approach has contributed significantly to expanding the therapeutic arsenal available against resistant tumors or those with a high risk of metastasis. This accumulated experience was decisive in leading a review that summarizes current knowledge and outlines future directions in the clinical development of this strategy.

New therapeutic horizons for a key molecular target

CXCR4 has been extensively validated as a therapeutic target. Developing new strategies therefore faces the challenge of improving efficacy without increasing toxicity, giving prominence to approaches that allow targeted, selective drug delivery. Designing functionalized nanoparticles, antibody-drug conjugates, photothermal molecules, or interfering RNA’s specifically aimed at CXCR4-positive cells opens new avenues to increase specificity and reduce adverse effects.

Looking ahead, prospects point to closer integration of diagnosis, patient selection, and treatment. Precision cancer medicine is moving toward combination therapies able to simultaneously recognize multiple tumor markers—such as CXCR4 together with others typical of tumor stem cells—helping overcome one of today’s main challenges: tumor plasticity and heterogeneity within the same tumor.

The review also argues for redesigning clinical trials. Instead of traditional models focused on specific tumor types, the authors highlight the value of so-called basket trials, which group patients by shared biomarkers—such as high CXCR4 expression—regardless of the tumor’s organ of origin. This approach would enable better patient selection and higher therapeutic response rates.

Meanwhile, molecular imaging technologies such as positron emission tomography (PET) with specific tracers are poised to play a fundamental role in patient detection, stratification, and monitoring. Agents like [68Ga]-Pentixafor allow non-invasive visualization of CXCR4 expression in tumors and target organs, facilitating both the selection of candidates for targeted therapies and real-time monitoring of response.

“Progress in personalized medicine for cancer treatment demands combining imaging technologies, molecular markers, and targeted therapies. CXCR4 is a paradigmatic example of how basic and applied research can converge to change clinical practice,” notes Ariana Rueda, first author of the study.

Reference article

Rueda A, Serna N, Mangues R, Villaverde A, Unzueta U. Targeting the chemokine receptor CXCR4 for cancer therapies. Biomarker Research. 2025;13:68. https://doi.org/10.1186/s40364-025-00778-y.

The Sant Pau Research Institute (IR Sant Pau) has secured funding for the creation of the Network for the Integrative Study of Synaptic Circuits and Their Role in Disease. This network will be coordinated by Dr. Àlex Bayés, head of the Molecular Synapse Physiology research group at IR Sant Pau. This thematic network, part of the State Program for Knowledge Transfer and Collaboration within the 2024–2027 State Plan for Scientific, Technical, and Innovation Research, is one of only two networks funded in the area of nervous system diseases. It was funded in a highly competitive call for proposals.

According to Dr. Bayés, “this network aims to foster scientific collaboration among basic and translational research groups working on synaptic circuits from very different, yet complementary, methodological approaches. The goal is to share knowledge and generate synergies to better understand the function of neuronal circuits and their dysfunction in neurodevelopmental disorders and neurodegenerative diseases.”

This is the third network of this kind led by Dr. Bayés from IR Sant Pau, following those established in 2015 and 2019. “We already have a solid track record in coordinating research networks. These initiatives not only help strengthen interdisciplinary research, but also increase the national and international visibility of our work and of IR Sant Pau.”

The network will consist of twelve research groups from different institutions across Spain, with experts in molecular biology, neuroscience, optical and electron microscopy, animal behavior, and optogenetics, among others. Network activities will include regular meetings, mobility programs for early-career researchers, and science outreach initiatives to bring research closer to the public. In addition, the network will promote data sharing, participation in collaborative research projects, and the application for new funding opportunities. The funding granted totals €28,000, to be distributed over two years.

With this initiative, IR Sant Pau reaffirms its commitment to high-quality basic and translational research, “which is essential for the later development of applied research,” says Dr. Bayés, as well as to building knowledge networks that contribute to scientific progress and the improvement of disease treatment. This new project further strengthens the institute’s position as a leader in synaptic circuit research and their role in brain health. It supports both the development of new research lines and the training of young scientists in a highly collaborative and innovative environment.

A recently published letter in The Lancet, signed by Dr. Juan Fortea and leading European experts in Alzheimer’s disease, celebrates the European Commission’s approval of lecanemab as a key milestone in transforming the diagnostic and therapeutic approach to the disease. The authors highlight that this decision finally enables a long-awaited paradigm shift in Europe: moving from symptom-based diagnosis in later stages to early biological diagnosis, opening the door to more precise, personalized, and effective care.

This advance, they emphasize, will benefit not only those who receive treatment with lecanemab, but also a much larger number of people with cognitive impairment, by fostering structural improvements in diagnostic, prognostic, and clinical follow-up systems. The introduction of this treatment requires a reorganization of care that may have broad positive effects beyond the drug itself.

However, the letter also delivers strong criticism of the European regulatory process. The authors express disappointment that the European Medicines Agency (EMA) has rejected the approval of donanemab, despite the scientific evidence and the fact that this treatment is already being used in many other countries around the world. This decision, along with the accumulated delays in the process, has led to a nearly two-year setback in access to disease-modifying therapies in Europe, with direct consequences for patients and their families.

The signatories call for deep reflection on the consistency and agility of regulatory evaluation processes in Europe and urge greater openness to emerging data and a more flexible, nuanced assessment of risk-benefit ratios that allows for informed decisions based on the most up-to-date evidence.

The letter concludes with a clear message: while regulatory caution is necessary, so too is therapeutic urgency in the face of a progressive and fatal disease like Alzheimer’s. Europe cannot afford to continue falling behind.

Reference:

Fortea J, Boban M, Engelborghs S, Frederiksen KS, Hort J, Kennelly S, Kramberger MG, Mehrabian S, Plantone D, Paquet C, Santana I, Scarmeas N, Solje E, Spiru L, Šutovský S, Vijverberg EGB, Winblad B, Jessen F. Regulatory asymmetry in Alzheimer’s disease care. Lancet. 2025. https://doi.org/10.1016/s0140-6736(25)00907-9.

An international team of researchers has discovered how cholesterol can disrupt the internal functioning of the heart by accumulating in the mitochondria of cardiomyocytes. They have also developed an experimental immunotherapy capable of reversing this process and restoring cellular energy production.

The study, recently published in the Journal of Lipid Research, was led by Dr. Vicenta Llorente-Cortés, researcher at the Lipids and Cardiovascular Pathology group of the Institute of Biomedical Research of Barcelona (IIBB-CSIC), part of the Spanish National Research Council (CSIC), the Sant Pau Biomedical Research Institute (IR Sant Pau), and the CIBERCV.

The research was conducted in collaboration with scientists from CIBERdem, the Institute of Molecular Biology of Barcelona (IBMB-CSIC), the University of Barcelona (UB), the Autonomous University of Barcelona (UAB), the University of California (USA), and the University of Toulouse (France).

The Heart, Vulnerable to Lipid Damage

The heart requires a high and constant energy supply and depends on the efficiency of its mitochondria to sustain continuous contraction of the cardiac muscle. In fact, cardiomyocytes (heart muscle cells) are among the most mitochondria-rich human cells—nearly a third of their volume consists of mitochondria. These organelles convert nutrients into energy through a process called oxidative phosphorylation, which is essential for heart function.

Several studies have indicated that under altered metabolic conditions—such as obesity, diabetes, or hypercholesterolemia—progressive mitochondrial dysfunction occurs, which worsens heart failure. This study identifies, for the first time, a precise cellular mechanism through which cholesterol esters, transported by lipoproteins, penetrate cardiomyocytes and accumulate inside their mitochondria, causing structural and functional impairments.

The LRP1 Receptor and Mitochondrial Cholesterol: A Direct Link

The researchers demonstrated that the LRP1 receptor, a protein located on the cell membrane of cardiomyocytes, is the main factor responsible for transporting esterified cholesterol from lipoproteins into cardiomyocytes. Under lipotoxic conditions, this cholesterol accumulates in mitochondrial membranes and interiors. The result is disruption of mitochondrial architecture, impairment of the respiratory chain, and a significant loss in energy production capacity.

“We have revealed a previously unknown mechanism: the cholesterol carried by lipoproteins doesn’t just affect blood vessels or accumulate in plaques—it actually penetrates the mitochondria of the heart. The accumulation of cholesterol esters in mitochondria compromises cellular respiration and, consequently, the function of the heart itself,” explains Dr. Vicenta Llorente-Cortés, CSIC researcher, lead author of the study, and coordinator of the CIBERCV and CIBERdem groups at IIBB-CSIC and IR Sant Pau.

To counter this harmful mechanism, the team developed an experimental immunotherapy based on monoclonal antibodies specifically targeting the P3 domain of the LRP1 receptor. This strategy achieves selective blockade that prevents the LRP1 receptor from transferring cholesterol esters—carried in the bloodstream by lipoproteins—into the cell interior.

A Multitechnic and Multiorganic Approach to Uncover a Hidden Mechanism

To conduct this research, the scientists used a combination of advanced bioenergetics techniques (University of California), mass spectrometry (University of Toulouse), and confocal and electron microscopy (IR Sant Pau and University of Barcelona). They used a rabbit model with a lipid profile similar to that of humans to simulate dyslipidemic conditions associated with cardiovascular disease (CSIC).

The researchers performed subcellular fractionation analyses to isolate mitochondria and quantify their lipid content, and used high-precision respirometry techniques to assess mitochondrial respiratory chain efficiency in the presence and absence of cholesterol accumulation in the hearts of the experimental model.

Anti-P3 Antibodies: An Experimental Solution with Great Potential

Trials conducted in the rabbit model—with a lipid and lipoprotein profile similar to that of humans—showed that this immunotherapy significantly reduces mitochondrial lipid load, particularly the content of cholesterol esters involved in cellular respiration. As a direct consequence, restoration of mitochondrial architecture was observed, including the recovery of mitochondrial aristae—key structures for cellular respiration. Furthermore, the therapy improves the efficiency of oxidative phosphorylation and normalizes ATP production, the energy molecule that powers heart contraction.

Another significant effect observed following treatment with anti-P3 antibodies was the improvement in the interaction dynamics between mitochondria and cytoplasmic lipid droplets, indicating a functional reorganization of cellular metabolism.

This therapeutic approach, both innovative and highly targeted, not only halts the damage caused by cholesterol accumulation but also reverses the effects on the heart’s energy machinery. According to the researchers, this strategy could potentially be applied in the future to treat various cardiovascular conditions where altered lipid profiles promote intracellular cholesterol deposition, such as in obesity, myocardial ischemia, or chronic hypercholesterolemia.

“Our experimental treatment allows us to act on the heart at a level that had not been targeted before: inside the cell, inside the mitochondria, where the vital energy of the cardiac muscle is generated,” emphasizes Dr. Vicenta Llorente-Cortés.

Responding to an Unmet Clinical Need

Cardiovascular diseases are responsible for one in three deaths worldwide. While current treatments have made significant advances in controlling traditional risk factors such as hypertension or plasma cholesterol, there is still no effective strategy to address intracellular metabolic damage in the heart, particularly mitochondrial damage.

This study proposes an entirely new approach: to intervene directly in the process that leads cholesterol to accumulate in the energy machinery of cardiac cells, thereby preventing the bioenergetic dysfunction that precedes heart failure.

“This discovery has clear clinical implications: it enables us to envision new therapies aimed at preserving mitochondrial function in patients with high cardiovascular risk. This is especially relevant in contexts where circulating cholesterol remains persistently elevated, and lowering it externally is no longer enough—we need to protect the heart from within,” concludes Dr. Llorente-Cortés.

Study Funding

This study was supported by the Carlos III Health Institute (ISCIII) through the cooperative research programs of the Biomedical Research Networking Centers in Cardiovascular Diseases (CIBERCV) and in Diabetes and Associated Metabolic Diseases (CIBERdem), as well as by funding from the European Regional Development Fund (ERDF). Additional funding came from the Spanish Ministry of Science, Innovation, and Universities, and from the Government of Catalonia through the Agency for Management of University and Research Grants (AGAUR). International collaborations were co-funded by research agencies in the United States and France, including the National Institutes of Health (NIH) and the Centre National de la Recherche Scientifique (CNRS).

Reference Article:

Benitez-Amaro A, Garcia E, LaChica Lhoëst MT, Polishchuk A, Zegri-Reiriz I, Vilades D, Guerra JM, Fernández-Del-Rio L, Mirabet S, Samouillan V, Shirihai O, Liesa M, Enrich C, Llorente-Cortés V. LRP1 immunotherapy enhances cardiomyocyte respiration by restricting cholesteryl ester accumulation in mitochondria. J Lipid Res 2025:100783. https://doi.org/10.1016/j.jlr.2025.100783

https://www.youtube.com/watch?v=1v9ONbGySCc&t=29s

A recent study has identified specific alterations in lipid metabolism associated with subclinical atherosclerosis in individuals with type 2 diabetes. This silent condition, known as atherosclerosis, occurs before cardiovascular events and causes a gradual narrowing of the arteries due to the buildup of fatty plaques. It is one of the main causes of complications in patients with diabetes.

The study, published in Cardiovascular Diabetology, was led by Dr. Dídac Mauricio, scientific director of the Diabetes and Metabolic Diseases area at CIBER (CIBERDEM) and researcher at Sant Pau Research Institute (IR Sant Pau), and Maria Barranco-Altirriba, first author of the article and researcher in the Bioengineering, Biomaterials and Nanomedicine area at CIBER (CIBER-BBN), also at the same institute. The study also involved other teams from CIBERDEM, CIBER-BBN, and the Obesity and Nutrition Physiopathology area (CIBEROBN) across different institutions.

The research analyzed more than 500 individuals, including patients with type 1 and type 2 diabetes and individuals without diabetes. It employed advanced lipid analysis technologies along with ultrasound imaging of the carotid arteries. Results indicated that nearly half of the participants displayed signs of subclinical atherosclerosis.

Lipid alterations in type 2 diabetes

“In patients with type 2 diabetes, we identified 27 distinct lipid species associated with the presence of atherosclerotic plaques in the arteries. Among the most implicated lipids were phosphatidylcholines and diacylglycerols, which showed both increases and decreases. Interestingly, the most marked changes were observed in people with type 2 diabetes who smoked or were not receiving treatment to control cholesterol,” explained Dr. Dídac Mauricio.

“These findings point to a significant alteration in lipid metabolism in type 2 diabetes, which could help identify high cardiovascular risk patients at an early stage. Furthermore, this opens the door to new studies aimed at finding more personalized prevention and treatment strategies based on each individual’s lipid profile,” the research team concluded.

Article reference:

Barranco-Altirriba M, Rossell J, Alonso N, Weber RJM, Ortega E, Lloyd GR, et al. Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes. Cardiovasc Diabetol. 2025;24(1):152. doi:10.1186/s12933-025-02701-z.

Intravenous administration of atorvastatin during acute myocardial infarction could become a new therapeutic strategy capable of limiting infarct size in patients with diabetic cardiomyopathy, a heart condition associated with diabetes.

This is suggested by a recent experimental study published in the journal Diabetes and led by Dr. Gemma Vilahur, head of the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases group at the Sant Pau Research Institute (IR Sant Pau) and researcher at the Spanish Network for Cardiovascular Research (CIBERCV), Carlos III Health Institute.

Atorvastatin is a widely used oral drug for lowering blood cholesterol levels and preventing the development of cardiovascular diseases. In this study, a new formulation of atorvastatin was used to allow intravenous administration during the acute phase of the infarction.

“The study shows, in an animal model of diabetic cardiomyopathy, that early administration of a single intravenous dose of atorvastatin after infarction reduces lesion size, improves cardiac function, and favorably modulates the processes of inflammation, cell death, and fibrosis that are triggered in the diabetic heart,” explains Dr. Vilahur.

An Unmet Medical Need

People with diabetes mellitus have a two- to threefold higher risk of suffering an acute myocardial infarction compared to individuals without the disease, and have a poorer post-infarction prognosis. Part of this vulnerability is due to both structural and functional alterations in the diabetic heart, known as diabetic cardiomyopathy. This condition is characterized by increased interstitial fibrosis at the cardiac level, persistent inflammation, and a poorer adaptation to ischemic stress.

Although various cardioprotective strategies have shown efficacy in experimental settings, the same benefits have not been replicated clinically. “This failure is partly attributed to the presence of comorbidities, which alter endogenous cardioprotective signaling pathways. Hence, the need to seek new strategies capable of protecting the heart against infarction in the presence of diabetes,” says Sebastià Alcover, first author of the article.

A Translationally Valuable Experimental Model

The study published in Diabetes uses a preclinical model that develops a diabetic cardiomyopathy phenotype with high similarity to the human condition, characterized by ventricular dysfunction and interstitial fibrosis.

In these animals with diabetic cardiomyopathy, acute myocardial infarction was induced by transient ligation (45 minutes) of the left anterior descending coronary artery, followed by 24 hours of reperfusion. Atorvastatin was administered to a group of animals intravenously and early after infarct induction, while another group received a vehicle. Additionally, for comparative purposes, two groups of normoglycaemic control animals (one treated and one untreated) were included.

“Intravenous atorvastatin treatment significantly reduced the infarction-induced cardiac damage in animals with diabetic cardiomyopathy compared to those that received the vehicle, achieving a benefit similar to that observed in the treated normoglycaemic animals. Moreover, this benefit was accompanied by better preservation of cardiac function,” adds Dr. Vilahur.

A Beneficial Effect Independent of the Lipid-Lowering Properties of Statins

According to Sebastià Alcover, “The observed benefits are not due to atorvastatin’s ability to lower circulating lipids, but rather to its capacity to inhibit the synthesis of isoprenoid intermediates by blocking the HMG-CoA reductase enzyme.” This inhibition leads to greater activation of the AMPK protein (a key enzyme in cardiac metabolism that is reduced in the presence of diabetes), reduced apoptotic cell death and inflammatory infiltration, as well as improved reparative fibrosis in the infarcted heart.

Clinical Outlook

Although this is an experimental study, the authors emphasize the importance of these preclinical results. “The possibility of having a drug that is widely used in clinical practice and capable of reducing cardiac damage in the presence of diabetic cardiomyopathy or other cardiovascular risk factors—as already shown previously by Dr. Vilahur’s group—deserves to be investigated in diabetic patients,” concludes Sebastià Alcover.

Reference Article

Alcover S, López S, Ramos L, Muñoz-García N, Gallinat A, Suades R, Badimon L, Vilahur G. Cardioprotection during myocardial infarction in diabetic cardiomyopathy. Diabetes 2025. https://doi.org/10.2337/db24-0510.

The Sant Pau Research Institute (IR Sant Pau) has formalized a strategic agreement with Ephion Health, a company specialized in developing artificial intelligence technologies for monitoring mobility in patients with movement-related diseases. Through this agreement, IR Sant Pau becomes a shareholder in the company, thereby consolidating a collaboration that began in 2021 and ensuring a long-term strategic partnership. This marks the first external startup in which IR Sant Pau is participating, representing a significant step forward in its innovation and technology transfer strategy.

Ephion Health was founded as a spin-off of Eurecat, Sant Joan de Déu, and The Collider at MWC, and from the beginning has worked with Dr. Luis Querol, a researcher at IR Sant Pau and an expert in peripheral neuropathies. Dr. Querol has led the clinical validation of Ephion Health’s technology applied to these conditions and will now join the company’s Advisory Board, continuing to provide clinical leadership in this area at Sant Pau.

In addition to his role as a researcher, Dr. Querol is a recognized authority in the field of peripheral neuropathies, further underscoring the importance of this collaboration. His involvement not only ensures that Ephion Health’s technology aligns with real clinical needs, but also exemplifies a new model of knowledge transfer in the biomedical field. The alliance goes beyond the typical relationship between researchers and companies, shifting from occasional external consulting to long-term strategic involvement. This enables innovation to reach clinical practice more quickly and effectively, directly benefiting patients and paving the way for similar future initiatives.

This agreement also represents an important milestone for IR Sant Pau, as Ephion Health becomes part of Sant Pau’s startup portfolio, reinforcing its commitment to innovation and technology transfer. Through this alliance, the goal is to promote a new model of collaboration between clinical researchers and companies, facilitating the implementation of innovative technologies in clinical care and directly benefiting patients.

Ephion Health’s technology makes it possible to obtain objective, quantifiable digital biomarkers related to patient movement, enabling a more accurate assessment of their progress. This tool represents a significant innovation compared to traditional evaluation methods, which often rely on subjective visual observations. The aim of the collaboration with IR Sant Pau is to validate this technology in peripheral neuropathies and develop a solution that can be applied in clinical practice, thereby addressing an unmet medical need.

In November 2023, the charity race L’Arriarem, organized by the family of Marc Riera i Castellà in his memory, raised over €96,000. Thanks to this momentum and all subsequent donations, €101,338 has been raised to date.

These donations have enabled the Sant Pau Research Institute (IR Sant Pau) to create a new line of research, led by Dr. Raúl Terés, Dr. Ana Sebio, and Dr. María Aguado, researchers from the Clinical Oncology Group, to study the effects of treatments on the quality of life of patients with Ewing sarcoma.

Until now, research on this type of cancer has mainly focused on determining the most effective therapeutic options and seeking new treatments to improve prognosis. However, the impact on patients’ quality of life is not as well understood, which limits the ability of healthcare systems to prevent and minimize these negative effects.

One of the first projects to be launched within this new research line will specifically analyze the effects of treatments for Ewing sarcoma on patients’ quality of life—covering physical, psychological, functional, occupational, economic, social, and reproductive aspects, among others.

Donations for Ewing Sarcoma research are being collected through the following page.

The goal is to reach €150,000, and all funds will be entirely dedicated to driving this new line of research on the impact of treatments on the quality of life of patients with Ewing sarcoma, with the aim of improving their comprehensive care and future.

Researchers at the Sant Pau Research Institute (IR Sant Pau), in collaboration with the Hospital de Sant Pau and the Josep Carreras Leukaemia Research Institute, have developed an innovative CAR-T cell therapy targeting the CD30 protein (HSP-CAR30), which has shown high efficacy in patients with refractory CD30+ lymphoma. In a phase I clinical trial, the results of which have been published in the prestigious journal Blood, this new CART30 has been shown to promote the expansion of memory T cells, leading to durable responses and improved clinical outcomes in treated patients.

Hodgkin lymphoma and other CD30+ lymphomas have posed a major challenge to the medical community, especially in relapsed or refractory cases where conventional treatments have so far shown limited effectiveness. Recently, CAR-T cell therapies have emerged as a promising alternative for the treatment of hematological malignancies, achieving highly positive results in leukemias and B-cell lymphomas. However, their application in CD30+ lymphomas has been limited due to the lack of persistence of the modified cells and the rapid relapse of patients. It is also worth noting the exceptionally low number of clinical trials in this area, which has hampered the development of new solutions.

Thanks to advances in genetic engineering and biotechnology, the IR Sant Pau team has managed to overcome these limitations with the creation of HSP-CAR30, an optimized version of CAR-T therapy that incorporates new strategies to improve the functionality and durability of therapeutic cells. This development represents a milestone in the fight against these types of cancer and opens new possibilities for patients who previously had very limited options.

Promising Results in the Phase I Clinical Trial

The phase I clinical trial included ten patients with relapsed or refractory classical Hodgkin lymphoma or CD30-positive T-cell lymphoma, with very positive results. According to Dr. Javier Briones, director of the Hematologic Oncology and Transplant Research Group at IR Sant Pau and head of the Hematology Department at Hospital de Sant Pau, and principal investigator of the study, “The most surprising finding of this study is that the overall response rate was 100%, something very uncommon in patients who have gone through multiple lines of treatment. Moreover, 50% of patients achieved complete remission, meaning the disease completely disappeared in imaging studies and clinical tests.”

Regarding the durability of the response, 60% of the patients who achieved a complete response remained in remission without signs of relapse after a median follow-up of thirty-four months. “This is crucial,” explains Dr. Briones, “because it indicates that the persistence of CAR-T cells in the body has a real and sustained impact on the disease, which is precisely what we look for in this type of therapy.”

From a safety perspective, the treatment showed a favorable profile, with no dose-limiting toxicities detected. Six patients experienced grade 1 cytokine release syndrome (CRS), and none developed neurotoxicity. Thus, the observed adverse effects were mild and manageable, reinforcing the feasibility of this therapy for clinical use.

One of the most notable aspects of the study is the high in vivo persistence of CAR30+ cells, which remained detectable in 60% of evaluable patients one year after infusion. In addition, during the peak of T-cell expansion, a predominance of central memory T cells (TCM) and stem cell-like memory T cells (TSCM-LIKE) was observed—both associated with treatment efficacy and durability.

A Promising Future for Patients with Refractory Lymphoma

“These results suggest that selecting the CD30 epitope and preserving less-differentiated T cells ex vivo may improve the efficacy of CAR-T therapy in patients with refractory Hodgkin lymphoma,” states Dr. Ana Caballero, attending physician in the Hematology Department and co-investigator of the trial, who emphasizes the importance of this finding: “If we can demonstrate in larger studies that this strategy works long-term, we may be looking at a paradigm shift in the treatment of refractory CD30+ lymphomas. This would bring hope to many patients who currently have very few viable therapeutic options.”

The study is registered at ClinicalTrials.gov (NCT04653649) and is currently in an expanded analysis phase to evaluate the efficacy of HSP-CAR30 in a larger number of patients. If these results are confirmed in future studies, this innovative therapy could represent a significant breakthrough in the fight against this disease.

HSP-CAR30: A Groundbreaking Study in Europe

The HSP-CAR30 treatment is the first European study of a CAR-T30 therapy to successfully complete its initial phase. The results of the phase I trial, now published in Blood, along with preliminary findings from the phase II trial, were presented at the 2024 Annual Meeting of the American Society of Hematology (ASH), one of the most important events for the scientific community, held late last year.

To date, 32 patients have been treated with HSP-CAR30 in the phase II trial, and the study has been expanded to include an additional 10 patients. According to Dr. Caballero, this expansion will strengthen the robustness of the results and establish a more solid foundation for the future development of this treatment. “The fact that over 55% of patients have achieved complete remission in phase II encourages us to move forward. These results are very hopeful for a population with limited treatment options,” said the researcher.

A New Approach to CAR-T Therapy in CD30+ Lymphoma

CAR-T cells act as a specialized army of the immune system. They are cells extracted from the patient and modified in the laboratory to recognize and attack specific cancer cells. In this case, HSP-CAR30 is designed to target the CD30 protein, which is present in tumor cells in Hodgkin lymphoma and other CD30+ lymphomas, and rarely expressed in healthy cells.

The challenge with previous CAR-T therapies was that, despite their initial effectiveness, many of these cells became exhausted too quickly or lost their ability to attack cancer over the long term. To overcome this barrier, researchers optimized the structure of HSP-CAR30 by directing it to a more stable region of the CD30 protein, preventing the tumor from evading the CAR-T cells by releasing CD30 fragments into the bloodstream.

Additionally, the manufacturing process has been refined to improve the quality and persistence of the modified T cells. An innovative strategy combining interleukin-21 (IL-21) with IL-7 and IL-15 has been implemented, promoting the expansion of T cells with long-term memory characteristics. This means that the treatment is not only effective in the short term but also offers a higher likelihood of lasting protection against the disease.

Dr. Laura Escribà, senior researcher and director of CART30 Production Quality Control, explains: “The goal of this optimization is to ensure that CAR-T cells are not only effective initially but remain active in the body for much longer. We want the patient’s immune system to retain a pool of defense cells ready to act in case the cancer tries to return.”

Funding and Support for the Study

Several organizations and foundations have supported the Sant Pau project. The Josep Carreras Foundation against Leukaemia and the Josep Carreras Leukaemia Research Institute played a key role in the project by acquiring essential equipment and providing funding for the production of therapies for the first ten patients. In this regard, the Josep Carreras Institute acquired two new cell production units that have been installed at Sant Pau. For the purchase of the first one, the Josep Carreras Foundation launched a fundraising campaign in 2018 titled “The Unstoppable Cell Factory.” The Josep Carreras Foundation has contributed over two million euros to support the launch of this trial.

This study was also made possible thanks to the support of other institutions and funding bodies. In particular, it has received backing from La Marató de TV3 (Exp. 20130710), the Carlos III Health Institute (ISCIII FIS PI15/1383 and PI18/01023; European Union), the “La Caixa” Foundation, the Agency for the Management of University and Research Grants (AGAUR, SGR2021/1139), and the Network for Advanced Therapies (RICORS, ISCIII; RD21/0017/0011; Next Generation, European Union). The study has also received support from the Blood and Tissue Bank (BST).

Reference Article:

Caballero AC, Ujaldón-Miró C, Pujol-Fernández P, Montserrat-Torres R, Guardiola-Perello M, Escudero-López E, Garcia-Cadenas I, Esquirol A, Martino R, Jara-Bustamante P, Ezquerra P, Soria JM, Iranzo E, Moreno-Martinez M-E, Riba M, Sierra J, Alvarez-Fernández C, Escribà-Garcia L, Briones J. HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma. Blood 2025;145:1788–801. https://doi.org/10.1182/blood.2024026758

The Sant Pau Research Institute (IR Sant Pau) expresses its great satisfaction and pride in the awarding of the Creu de Sant Jordi to Dr. Montserrat Baiget—an honor granted by the Government of Catalonia to individuals who have rendered outstanding service to the country in the civic, cultural, or scientific fields.

This award recognizes an extraordinary professional career marked by commitment, innovation, and dedication to the advancement of science and public health. Dr. Baiget has been a key figure in the development of human genetics in Catalonia and throughout Spain, where, as early as the 1970s, she led the creation of the first Genetics Service at Sant Pau Hospital—also the first of its kind in the country—which she directed until her retirement in 2017.

Over nearly five decades, Dr. Baiget has been a true pioneer, particularly in the field of genetic and molecular diagnosis of hereditary diseases such as thalassemia, hemophilia, and muscular dystrophy. Her vision and drive made it possible to incorporate the most advanced molecular genetics techniques into our healthcare system long before they became standard practice, paving the way for personalized medicine and pharmacogenetics.

She was also one of the first to implement the study of genes involved in hereditary cancer, offering thousands of women at high risk of developing breast or ovarian cancer the chance to follow personalized prevention and treatment protocols. Her work has had a direct and profound impact on the lives of many individuals and families.

In the research field, Dr. Baiget played a decisive role in establishing IR Sant Pau as a CERCA center. She has published over 450 scientific articles in international journals, presented nearly 650 papers at conferences, contributed to around thirty chapters in specialized books, and supervised 16 doctoral theses, all awarded the highest distinction.

Her leadership has been evident both in directing the Genetics Service and in advancing research at Sant Pau, helping to build a model of scientific and human excellence. A full member of the Royal Academy of Pharmacy, Dr. Baiget has broken barriers in a historically male-dominated environment, becoming a role model for new generations of women scientists.

Dr. Baiget expressed how deeply moved she is by this recognition:
“Throughout my life, I’ve received many awards, but the one that has made me happiest—by far—is the Creu de Sant Jordi. Because it feels like it comes from home, from my country.”

She also emphasized that, even though she began her career in a world dominated by male doctors, she never felt questioned for being a woman or a pharmacist. “When I started at Sant Pau, it was a world of men and doctors. I’m a pharmacist. But I don’t recall any moment when my work was questioned because I was a woman or a pharmacist. I’ve always been treated equally. That’s the truth. I’ve had—and still have—great friends in this institution.”

Finally, she expressed gratitude for the opportunity Sant Pau gave her to grow professionally. “When I started out, I was lucky that the stars aligned in my favor: a hospital, a department, supervisors who let me do my work. With that supportive foundation, I launched studies that were the first of their kind in Catalonia and Spain. And I think that being a pioneer is part of what the Creu de Sant Jordi is recognizing.”

The Creu de Sant Jordi is, without a doubt, a well-deserved tribute to a brilliant career and a collective gesture of appreciation for her irreplaceable contributions to medicine, science, and society.

From IR Sant Pau and the Sant Pau Hospital, we wholeheartedly congratulate Dr. Montserrat Baiget and share in the joy of this meaningful recognition.

Thank you for everything, Dr. Baiget—and congratulations!

A study involving researchers from the Sant Pau Research Institute (IR Sant Pau) and the Universitat Autònoma de Barcelona, led by the University of Oxford, has analyzed trends in colorectal cancer in the United Kingdom between 2000 and 2021 using real-world primary care clinical databases. The research, published in The American Journal of Gastroenterology, has revealed a steady increase in early-onset colorectal cancer (in people under 50) over the past two decades.

According to the study, although the overall incidence of colorectal cancer has stabilized—thanks in part to screening programs introduced in 2006—there has been a noticeable rise among younger populations. “It’s not an explosion of cases in absolute numbers, but the concern is that this increase is sustained in an age group where this trend was not typically seen,” explains Dr. Patricia Pedregal, from the Digestive Pathology Research Group at IR Sant Pau and a specialist in the Digestive Diseases Department at Hospital Sant Pau, first author of the study.

The study is based on data from over 150,000 patients diagnosed in the U.K., with a total cohort exceeding 35 million people. “One of the strengths of this study is that by using real population-based databases, we’re not extrapolating estimates—we’re working with data directly recorded by primary care physicians,” adds Dr. Pedregal.

Screening Works, but Doesn’t Reach Everyone

The analysis also proves that the implementation of screening programs has had a positive impact on older age groups, stabilizing or even reducing incidence among people aged 60 to 79, and slightly improving survival in that group. However, individuals under 50 are not included in these programs, which may partly explain the increase in that population.

“Stabilization in older adults confirms that screening works. But we need to start a conversation about whether we should begin earlier. It’s also essential for doctors and patients to be alert to warning signs—even in younger people,” emphasizes Dr. Pedregal.

Stagnant Survival Rates

Another key finding of the study is the limited improvement in survival rates over time, despite advances in treatments. Overall survival one year after diagnosis is 78%, but this drops to 51% at five years and 38% at ten years. “We would expect to see a clearer improvement with today’s treatments, but that’s not reflected in the data. This suggests that beyond treatment, there are structural and diagnostic factors we need to improve,” warns the researcher.

The study also confirms that the United Kingdom still has poorer colorectal cancer survival rates compared to other European countries with similar healthcare systems, although the reasons for this are not entirely clear.

Research with Real-World Data

One of the major methodological contributions of this study is the use of real-world data from primary care records rather than traditional cancer-specific registries. This allowed for a more representative cohort of the general population and a very extensive longitudinal follow-up—over two decades in some cases.

“Cancer registries are created for specific purposes, and many times estimates are used to calculate incidence and prevalence. In our case, all calculations come from an integrated database with real information from patients treated within the U.K. public health system. That gives our results greater robustness and validity,” notes Dr. Patricia Pedregal.

In addition, these databases make it possible to analyze large-scale epidemiological patterns without the need to individually recruit patients—something that would be virtually unfeasible in a traditional hospital setting. “Having a sample of over 35 million people and more than 20 years of data is a unique opportunity to understand the true evolution of colorectal cancer in the population. This information can help shape public health policies, optimize screening programs, and in the future, guide more personalized treatment strategies,” adds the researcher.

This approach also highlights the role of primary care not just as the first level of care, but as a key source of information for biomedical research. “These databases reflect the real activity of general practitioners and make it possible to generate evidence applicable to routine clinical practice. They are a powerful tool for advancing cancer research,” concludes Dr. Pedregal.

A Grant That Supports International Research

This research was made possible thanks to a two-month research stay by Dr. Patricia Pedregal at the University of Oxford, as part of her doctoral thesis. It was supported by a 2024 grant from the Fundació Privada for placements in biomedical research centers or leading hospitals.

During this stay, Dr. Pedregal joined the team at the University of Oxford’s Centre for Statistics in Medicine, which specializes in the analysis of real-world clinical data. This direct collaboration has already led to new scientific projects. Currently, two additional studies are underway: one using data from six European countries and another focused again on the U.K. There are also efforts to replicate this research using data from the Catalan healthcare system.

“This stay allowed me to learn firsthand how leading groups in clinical epidemiology and large database analysis work. It was a key experience in my development as a researcher and has opened up new collaboration opportunities that will undoubtedly impact future research lines in digestive health and cancer,” says Dr. Patricia Pedregal.

Reference Article

Pedregal-Pascual P, Guarner-Argente C, Tan EH, Golozar A, Duarte-Salles T, Rosen AW, Delmestri A, Man WY, Burn E, Prieto-Alhambra D, Newby D. Incidence and survival of colorectal cancer in the United Kingdom from 2000-2021: a population-based cohort study. Am J Gastroenterol 2025. https://doi.org/10.14309/ajg.0000000000003460

The outreach projects of the Iberoamerican Cochrane Centre (CCIb) will be visible on the streets of Barcelona during this Holy Week through a communication campaign aimed at bringing scientific health evidence closer to the public. The campaign, which began this past Tuesday, April 15, and will run through Monday, April 21, consists of a series of posters displayed in about ten bus shelters across the city. These posters pose general health-related questions designed to spark public curiosity.

Does listening to music help relieve insomnia? or Does intermittent fasting help with weight loss? are some questions featured on the posters. By scanning a QR code, interested individuals can access the answers and learn more about these and other health interventions. The campaign is supported by the Spanish Foundation for Science and Technology (FECYT) and the Organization of Consumers and Users (OCU), along with Hospital Sant Pau in Barcelona and the Sant Pau Research Institute (IR Sant Pau), with which the CCIb is affiliated.

“With this campaign, we aim to raise public awareness of our main outreach projects, such as Nutrimedia, Cochrane Responds, and Keys to Critical Thinking in Health, as well as invite interested citizens to participate in our studies to help improve science communication,” says Gonzalo Casino, Knowledge Transfer Manager at the CCIb.

Cochrane Responds is a monthly outreach project focused on the Cochrane systematic reviews that are of most interest to the public. The OCU has collaborated on this initiative since its launch in 2020. To date, over fifty health interventions have been featured in various formats, applying scientific evidence to communication efforts.

Nutrimedia, a joint project of the CCIb and Pompeu Fabra University in Barcelona, aims to provide citizens with scientific data and criteria to make informed decisions about nutrition and health. Its distinctive feature is that it evaluates how trustworthy certain health claims are—especially those circulating in the media and on social networks—while also answering questions submitted by the public.

Other projects featured in this campaign include Keys to Critical Thinking in Health and SimpleGRADE, which explains the certainty of evidence and the GRADE system in plain language.

A team from the Sant Pau Research Institute (IR Sant Pau), in collaboration with the Catalan Down Syndrome Foundation, has published in the journal Annals of Neurology the largest study to date on brain metabolism—measured through fluorodeoxyglucose positron emission tomography (FDG-PET)—in adults with Down syndrome. The results prove that Alzheimer’s-related neurodegeneration, as measured by FDG-PET, begins many years before the first symptoms appear and can already be detected from age 35.

“In this study, we analyzed how brain metabolism changes in people with Down syndrome throughout the different stages of Alzheimer’s disease: from those who show no symptoms yet, through a prodromal stage where cognitive symptoms begin to appear without affecting functionality, all the way to the dementia stage,” explains Dr. José Enrique Arriola-Infante, first author of the study, who conducted the research at IR Sant Pau and currently works at the Torrecárdenas University Hospital (Almería, Spain).

A Unique Model for Studying Alzheimer’s

People with Down syndrome have a unique genetic predisposition: overexpression of the APP gene due to the triplication of chromosome 21 leads to overproduction of beta-amyloid protein, making them a natural genetic model for Alzheimer’s. It is estimated that over 90% of this population will develop the disease over their lifetime.

“The age at which boys and girls with Down syndrome start showing reduced brain metabolism is much earlier than in healthy controls. From age 35, we already see significant differences,” Dr. Arriola points out. “From a very young age, even before symptoms appear, they already show brain hypometabolism in regions typically affected by Alzheimer’s disease: the parietal and temporal lobes.”

Rigorous Design with Imaging Techniques and Biomarkers

The study is part of the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI), an internationally recognized cohort. A total of 105 adults with Down syndrome in different clinical stages of Alzheimer’s disease—asymptomatic, prodromal, and with dementia—were included, along with a group of 71 healthy controls without intellectual disability.

All participants underwent an FDG-PET scan, which visualizes glucose consumption as a marker of brain activity. Structural MRI scans were also performed, along with cerebrospinal fluid extractions to analyze key biomarkers such as beta-amyloid, phosphorylated tau, and neurofilament light chain (NfL), the latter being an indicator of axonal damage.

Images were analyzed using advanced voxelwise statistical techniques, which allow researchers to detect abnormalities at each point in the brain without needing to predefine specific regions. “This analysis allows us to skip any a priori assumptions about anatomical regions and explore where in the brain the effects are occurring. It helps detect the areas where changes emerge earliest,” explains Dr. Alexandre Bejanin, neuroscientist with the Neurobiology of Dementia group at IR Sant Pau and senior author of the paper. “This method is more sensitive than regional analyses, where signals might be missed. It lets us map the exact topography of hypometabolism.”

Age—Not Sex or Disability—as a Key Factor

Beyond brain metabolism, the team also examined how variables such as sex or the degree of intellectual disability might influence outcomes. The findings were clear: the only truly significant factor was age. “Sex did not significantly affect brain metabolism, nor did the degree of intellectual disability,” summarizes Dr. Arriola. “What we did see is that age is directly related to metabolic decline. The older the person, the closer their pattern is to typical Alzheimer’s.”

Dr. Bejanin adds: “The effect of age is stronger in people with Down syndrome than in the general population. That’s because they are essentially all genetically predisposed to develop Alzheimer’s. So, age functions like a marker of the silent progression of the disease.”

Link to Alzheimer’s Biomarkers

One of the most important findings was the strong association between brain hypometabolism and biomarker levels in cerebrospinal fluid. In particular, neurofilament light chain (NfL), a marker of axonal damage, was found to be the most closely associated with metabolic loss.

“What we’ve seen is that the biomarker most related to metabolism is NfL, which also measures neurodegeneration,” explains Dr. Bejanin. “This confirms that the hypometabolism detected by PET is a highly reliable reflection of the disease process.”

The study also found associations with beta-amyloid (Aβ42/40) and phosphorylated tau (p-tau 181) levels, reinforcing the interpretation of hypometabolism as an indicator of Alzheimer’s-related degeneration.

Implications for Clinical Trials and Early Treatment

Although FDG-PET is a technique with some logistical limitations—such as requiring the injection of a radioactive tracer—the study highlights its usefulness as a tool for early diagnosis in people with Down syndrome. “What our work shows is that this test’s ability to detect neurodegeneration is strong even in the earliest stages, when individuals are still asymptomatic,” says Dr. Arriola. “This can help us better select participants for clinical trials of treatments aimed at modifying the course of the disease.”

Dr. Bejanin also emphasizes its clinical value. “We already knew this technique is sensitive for detecting neurodegeneration in sporadic Alzheimer’s. What we’re showing now is that it’s also effective in a genetic form like the one seen in Down syndrome.”

Looking Ahead

The team is already working on complementary research lines. “We’re comparing FDG-PET with other neuroimaging techniques such as structural MRI and cerebral perfusion imaging. This will help us determine which is more sensitive for detecting neurodegeneration in the very early stages,” says Dr. Bejanin. These MRI-based techniques would also be less invasive, as they don’t require injection of radioactive tracers.

Reference Article

Arriola-Infante JE, Morcillo-Nieto AO, Zsadanyi SE, Franquesa-Mullerat M, Vaqué-Alcázar L, Rozalem-Aranha M, Arranz J, Rodríguez-Baz Í, Maure-Blesa L, Videla L, Barroeta I, Del Hoyo Soriano L, Benejam B, Fernández S, Sanjuan-Hernández A, Giménez S, Alcolea D, Belbin O, Flotats A, Camacho V, Lleó A, Carmona-Iragui M, Fortea J, Bejanin A. Regional brain metabolism across the Alzheimer’s disease continuum in Down syndrome. Ann Neurol 2025. https://doi.org/10.1002/ana.27226

A study led by Dr. Ariadna Tibau, researcher at the Sant Pau Research Institute (IR Sant Pau) and oncologist at Hospital de Sant Pau, was recently published in the journal JAMA Network Open. The article systematically analyzes for the first time which factors contribute to a faster transition from accelerated to regular approval of oncology drugs by the U.S. Food and Drug Administration (FDA). The study also included participation from Alejandra Romano, oncology resident at Hospital Sant Pau, and Dr. Ignasi Gich, researcher with the Clinical Epidemiology and Health Services Group at IR Sant Pau.

The FDA’s accelerated approval pathway, in place since 1992, allows new drugs for serious conditions to reach patients more quickly. This route is based on preliminary results using surrogate clinical endpoints, but continued approval of these drugs is contingent on follow-up confirmatory trials demonstrating their efficacy and safety.

This international, retrospective study evaluated 102 indications for oncology drugs that received accelerated approval between 1992 and 2022 and subsequently gained full FDA approval before August 31, 2024. The findings show that conversion to full approval occurs more rapidly when certain characteristics are present at the time of initial approval: priority review designation, absence of serious safety warnings, initiation of confirmatory trials before approval, and an intermediate or high clinical benefit based on the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS).

“Our analysis shows that drugs with greater therapeutic potential and no major safety concerns at the time of accelerated approval tend to complete confirmatory trials more quickly and receive full approval sooner,” explains Dr. Ariadna Tibau. “This information can be very useful for regulators and clinicians, as it helps anticipate which drugs are more likely to demonstrate real benefit for patients.”

The study also highlights that among the confirmatory trials analyzed, those that showed a significant benefit in overall survival or quality of life were completed in less time. In contrast, drugs with less clear results took significantly longer to achieve full approval, which may expose patients to treatments of uncertain value over extended periods.

One of the key contributions of this work is the use of the ESMO-MCBS scale to assess the clinical benefit of drugs. According to Dr. Tibau, “It is essential that approval mechanisms be accompanied by tools that help prioritize therapies with the highest real clinical value. In this regard, the ESMO-MCBS can support more informed decision-making both in regulatory settings and clinical practice.”

The study was conducted in collaboration with leading research centers such as Harvard Medical School, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, the Vall d’Hebron Institute of Oncology (VHIO), Queen’s University (Canada), and the Clinical Epidemiology team at Hospital de Sant Pau. The work was supported by the Kaiser Permanente Institute for Health Policy, with grants from Arnold Ventures, The Commonwealth Fund (for Dr. Kesselheim), and the Alfonso Martín Escudero Foundation (for Dr. Tibau).

Reference Article:

Tibau A, Hwang TJ, Romano A, Borrell M, Gich I, Molto C, Kesselheim AS. Factors in time to full approval or withdrawal for anticancer medicines granted accelerated approval by the FDA. JAMA Netw Open. 2025;8:e252026. https://doi.org/10.1001/jamanetworkopen.2025.2026