The Sant Pau Research Institute (IR Sant Pau) and the CADASIL Spain Association (ACE) have strengthened their collaboration with a new contribution of 15,000 euros. This is aimed at advancing the research being carried out at the center on CADASIL, a hereditary disease that affects the small blood vessels in the brain and can cause recurrent strokes, severe migraines, cognitive impairments, and mood disorders.

This new donation, which adds to those made in previous years, highlights ACE’s commitment to biomedical research and to the work of the scientific teams striving to improve the diagnosis and treatment of this rare disease.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a condition caused by mutations in the NOTCH3 gene, which alter the structure of the walls of cerebral blood vessels and impair blood flow. Despite advances in understanding its genetic basis and mechanisms of progression, no curative treatment currently exists, and clinical management is primarily focused on controlling symptoms and vascular risk factors.

The new financial contribution will help advance a drug repurposing project being developed by the Pharmacogenomics and Neurovascular Genetics Research Group at IR Sant Pau, led by Dr. Israel Fernández. The team focuses on identifying drugs already approved for other indications that may have a beneficial effect in CADASIL. This strategy helps reduce research time and costs, as it builds on compounds that have already demonstrated safety in humans. The ultimate goal is to discover new therapeutic pathways that could slow down or reverse the progression of the disease.

With this new contribution, ACE continues a collaboration that has been ongoing for years with IR Sant Pau. Over this time, the association has consistently supported the funding of various research lines related to the genetic, molecular, and clinical understanding of CADASIL. This has facilitated the acquisition of materials, the performance of specific analyses, and participation in national and international collaborative projects.

This continued involvement has made it possible to keep research on this rare disease active, where available resources are often limited, and has strengthened a relationship of trust and cooperation between ACE and the IR Sant Pau scientific team. Thanks to this support, researchers have been able to generate results that contribute to a more profound understanding of the disease mechanisms and to guide new therapeutic research directions.

IR Sant Pau deeply appreciates the trust and support of ACE, which are essential for advancing scientific knowledge and promoting new strategies for CADASIL, with the goal of improving the quality of life of affected individuals and their families.

An international team of researchers has demonstrated that the tetravalent dengue vaccine Qdenga provides significant protection against the disease under real-world conditions during the major 2024 epidemic in São Paulo, Brazil. The study, published in the journal The Lancet Infectious Diseases and led by Dr. Otavio Ranzani, head of the DataHealth Lab group at the Sant Pau Research Institute (IR Sant Pau). Together with Dr. Julio Croda, Fiocruz, Brazil, provides the first evidence of the vaccine’s effectiveness following its approval.

Dengue is one of the fastest-growing mosquito-borne viral diseases worldwide, driven by climate change and the spread of the Aedes mosquito. Each year it causes millions of infections in tropical and subtropical regions, and more outbreaks are being detected in non-endemic areas, such as Europe. In this context, having effective vaccines with solid real-world effectiveness data is an urgent public health need.

A Groundbreaking Study Conducted Amid an Epidemic

The study was carried out in the state of São Paulo, the epicenter of the 2024 dengue epidemic, which recorded tens of thousands of cases. Health authorities decided to prioritize vaccination in adolescents aged 10 to 14, since in endemic areas this age group accounts for a large proportion of symptomatic cases and faces a considerable risk of hospitalization. This age range is also consistent with the current WHO vaccination recommendation. In addition, this group is highly exposed to the mosquito vector due to their daily activities and mobility, which increases the likelihood of infection. In this context, an immunization campaign was launched that, over the course of the year, administered nearly 690,000 doses of Qdenga.

The research team analyzed more than 90,000 adolescents who presented with acute fever and underwent specific laboratory tests (NS1 antigen detection or PCR). Using a design known as test-negative case-control, they compared the proportion of vaccinated individuals among those who tested positive for dengue and those who tested negative, allowing estimation of the real-world effectiveness of the vaccine under everyday conditions.

Results showed that after a single dose, the vaccine reduced symptomatic dengue cases by around 50% with the first dose and by 62% with the second, and hospitalizations by 68%. Protection began 14 days after the first dose, was maintained during the first three months, and then declined, reinforcing the importance of completing the recommended and approved two-dose schedule for longer-lasting protection.

“This study design allowed us to quickly and accurately evaluate the vaccine’s effectiveness amid an epidemic, using real patient data from the healthcare system. It is a powerful approach to generate evidence in health emergencies,” explained Dr. Ranzani.

A Robust Study, Though With Some Limitations

The study has several strengths that reinforce the validity of its results. It is the first evaluation of the Qdenga vaccine under real-world conditions, beyond clinical trials, and was conducted in an exceptional context: a major dengue epidemic in São Paulo. The large number of adolescents included in the analysis enabled robust estimates of effectiveness, while the use of a test-negative case-control design reduced the risk of biases related to healthcare-seeking behavior. In addition, results remained consistent across different analytical methods, providing greater confidence in the conclusions.

However, the authors also noted some limitations that should be considered. Vaccine coverage achieved was relatively low, which limited the study’s power to analyze effectiveness after the second dose in detail. Information on prior dengue immunity among adolescents was also unavailable. Finally, serotype circulation during the outbreak was concentrated on DENV-1 and DENV-2, preventing evaluation of effectiveness against all four virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4).

“Although the study has some limitations, the findings consistently show that Qdenga protects against dengue and reduces the risk of hospitalization. These data will be critical in guiding countries’ vaccination decisions,” emphasized Dr. Ranzani.

International and European Relevance

Until now, evidence on the vaccine was based solely on controlled phase 3 clinical trials. This new study is the first to demonstrate its impact on the general population under real-world conditions, in the midst of a major epidemic, reinforcing its value for public health decision-making.

Although Europe is not an endemic region, the spread of the Aedes mosquito linked to climate change has favored the emergence of local dengue outbreaks in countries such as France and Italy, while imported cases among travelers continue to rise. Catalonia is an example of this trend: between 2022 and 2024, more than 500 imported dengue cases were reported, mainly in people who had traveled to endemic regions. However, episodes of local transmission have already been detected, with two cases in 2018–2019, one in 2022, and an outbreak in 2024.

“Although in Catalonia and Europe most cases are still imported, the risk of local transmission is increasing. Having effective vaccines like Qdenga can make a difference in responding to future outbreaks and protecting travelers,” said Dr. Ranzani.

Public Health Implications

The results of this study are highly practical. On one hand, they support the use of Qdenga in emergency campaigns in endemic countries, where dengue outbreaks can quickly overwhelm health systems and cause a high number of hospitalizations. Evidence indicates that a single dose already provides significant protection within a few weeks, making the vaccine a key tool to curb ongoing epidemics and reduce hospital burden.

On the other hand, the data are also relevant for non-endemic countries, where most cases are imported but the risk of local transmission is increasing. In this context, the vaccine may play an essential role in traveler prophylaxis and in the prevention of autochthonous outbreaks, strengthening health system preparedness against the spread of the Aedes mosquito.

“The message is clear: the vaccine works and can protect against both mild and severe dengue. But to ensure sustained protection, we must complete the vaccination schedule. Our results can help policymakers and regulatory agencies better plan vaccination strategies,” added Dr. Ranzani.

The study was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) in Brazil and involved an international group of researchers, including collaborators from the United States, in partnership with the São Paulo State Health Department.

A New Research Group at IR Sant Pau

This study is part of the first investigations of the DataHealth Lab, a newly established group at IR Sant Pau under the direction of Dr. Otavio Ranzani. Its creation responds to the need for teams capable of generating scientific evidence that is not only methodologically rigorous but also has a tangible impact on population health and public policy.

The DataHealth Lab is built on three main pillars: Epidemiology, Data Science, and Implementation Science. From this multidisciplinary perspective, the group addresses some of the most pressing challenges in global health. These include the effects of climate change and exposure to environmental pollutants on health, the growing threat of respiratory and emerging infections, the impact of antimicrobial resistance on health systems, and the improvement of critical care. Another key focus is the evaluation of the real-world effectiveness of vaccines, a line of work directly connected to the newly published study on the dengue vaccine.

The lab is also committed to innovation in critical care, exploring new strategies such as adaptive clinical trials, the use of telemedicine to improve care under high-pressure conditions, and the integration of artificial intelligence tools to support clinical decision-making. All this is pursued with a vision of open, inclusive, and sustainable science, oriented toward generating knowledge useful to society and health systems.

With the creation of the DataHealth Lab, IR Sant Pau strengthens its leadership in biomedical research and consolidates its role as a benchmark in the use of advanced data to tackle major public health challenges nationally and internationally.

Article Reference:

Ranzani OT, Lazar Neto F, Mareto LK, Brumatti TS, de Oliveira RD, da Silva PV, dos Santos ER, D’Agostini TL, De Paula RAC, Dean NE, Ko AI, Cummings DAT, Andrews JR, Hitchings MDT, Croda J. Effectiveness of the TAK-003 dengue vaccine in adolescents during the 2024 outbreak in São Paulo, Brazil: a test-negative, case–control study. *Lancet Infect Dis* 2025. https://doi.org/10.1016/s1473-3099(25)00382-2

Dr. Saül Martínez-Horta, researcher at the Sant Pau Research Institute and neuropsychologist in the Movement Disorders Unit of the Neurology Department at Sant Pau Hospital, has been appointed the new Coordinator of the Neuropsychology Section of the Spanish Society of Neurology (SEN). This appointment represents recognition of both his clinical and research career as well as the growing role that neuropsychology plays within neurology.

The SEN, founded in 1949, is the leading scientific entity in neurology in Spain. With nearly 4,000 members, its mission is to promote scientific and clinical progress in neurology, foster continuing education for professionals, improve patient care for those with neurological diseases, and encourage research and outreach to advance the neurological health of the population.

Within this society, the Neuropsychology Section —created in 2012— aims to strengthen the presence of the discipline in the neurological field. Its main lines of action include developing specialized training programs, creating a nationwide map of neuropsychology, accrediting professional activity, drafting its manuals and guidelines, and establishing collaboration agreements that foster research and clinical practice.

Neuropsychology has undergone remarkable progress recently, driven by several factors: advances in neuroimaging, technologies applied to assessment, the development of new treatments for neurological diseases, and increasingly precise identification of prodromal and asymptomatic phases of neurodegenerative processes. In this context, the new leadership of the Section faces challenges focused on consolidating professional recognition, promoting multicenter research, and transferring knowledge into daily clinical practice.

According to Dr. Martínez-Horta, “this appointment is also a collective responsibility: neuropsychology must continue to grow hand in hand with neurology, and this is only possible through collaboration among professionals and institutions.” He adds, “our goal is for neuropsychology to be seen not only as an assessment tool but as a key element in understanding and comprehensively addressing neurological diseases.”

This appointment is also a source of pride for the Sant Pau Research Institute and Sant Pau Hospital, which congratulate Dr. Martnez-Horta on this new responsibility. They wish him great success in a stage that will further strengthen the role of neuropsychology in Spanish neurology.

For the third consecutive year, Club Natació Banyoles (CN Banyoles) has made a donation to the Sant Pau Research Institute to support the project dedicated to the study of Ewing Sarcoma, a rare type of cancer that mainly affects children and adolescents.

The funds come from the Marc Riera Castellà Memorial, a charity water polo tournament organized by the club in memory of Marc Riera, a young athlete who lost his life to this disease. All proceeds from the tournament have been allocated to support the research being carried out at Sant Pau.

A project born from solidarity

The Ewing Sarcoma research project was launched thanks to the initiative of Marc’s family and the charity race Arriarem, which mobilized hundreds of people to raise funds and raise awareness about the disease. Since then, various activities and organizations have joined the cause, consolidating a community-driven movement that has already raised over €100,000 for research.

In the case of the Marc Riera Castellà Memorial, the latest edition held in 2025 raised €6,000. Altogether, over its three editions, Club Natació Banyoles has contributed €11,500 to the Sant Pau project.

Research focused on patients’ quality of life

The project, led by Dr. Raúl Terés, Dr. Ana Sebio, and Dr. María Aguado, researchers from the Clinical Oncology Group at IR Sant Pau, aims to analyze the impact of treatments on patients’ quality of life, addressing physical, psychological, social, occupational, and reproductive aspects.

This line of research is pioneering because it not only studies therapeutic effectiveness but also the overall well-being of patients, with the goal of developing strategies to improve life after treatment.

Those who wish can continue supporting this project through the website.

The ultimate goal of the project is to reach €150,000, which will be fully allocated to this line of research.

Mariona’s Adventure has arrived at the Barcelona Zoo with resounding success. All the scheduled workshops were fully booked, and participants enjoyed a day of scientific discovery in a unique setting where biomedical research and environmental education came together. Held on Saturday, September 27, this mission marked a major highlight of the project’s second edition, as for the first time it moved beyond Tibidabo Amusement Park to reach another emblematic space in the city. The goal is to expand outreach settings and grow the community that accompanies Mariona in her scientific adventures.

This mission was dedicated to the nervous system and was carried out in collaboration with both the science communication team of IR Sant Pau and the educational staff of the Barcelona Zoo. They joined forces to offer a complete and enriching experience. IR Sant Pau professionals prepared interactive workshops to explain in a simple and engaging way how the brain works and which structures are part of the nervous system. Through games such as science bingo and assembling a paper puzzle, children learned playfully about the functions that allow us to think, feel, and move. They also had the chance to see and handle 3D models of real brains—an experience that helped them better understand the size and characteristics of this organ, as well as the changes it undergoes when it becomes ill and its cells stop functioning. In addition, outdoors, a giant science memory game challenged the memory of both children and adults, turning learning into a collective and participatory game.

Meanwhile, the zoo’s educational team contributed their expertise to explain the role of the nervous system in the animal world. Through their outreach work and the zoo animals themselves, they showed how the senses are essential for survival and adaptation in each species. Families were able to closely observe examples demonstrating how night vision, smell, or enhanced hearing are key to communication and defense in animals in their natural habitats.

In this way, science and nature came together in a privileged setting, creating an immersive experience that allowed participants to discover the complexity and beauty of the nervous system in both humans and animals. The activity reinforced the idea that scientific research and environmental education share a common goal: fostering curiosity, knowledge, and respect for life.

You can find more information on the website:

https://www.santpau.cat/es/web/public/mariona-investigadora

The Mariona Project

The “Mariona Investigadora” project is an educational and outreach initiative developed by IR Sant Pau. Mariona is a character that symbolizes an eight-year-old girl passionate about science and medicine, whose purpose is to inspire children and young people to explore the world of scientific research. It is precisely at this age—around eight years old—that girls often begin to lose interest in science, due to persistent stereotypes and the lack of role models. This project seeks to address that gap.

Through a series of missions and challenges designed to be carried out at Tibidabo Amusement Park and at the Barcelona Zoo, Mariona encourages children to discover the secrets of the human body. They take part in scientific experiments and learn about the importance of adopting a healthy lifestyle.

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

Science With a Gender Perspective

IR Sant Pau continuously fosters dialogue with society, aligned with its RRI plan and with its objectives for Scientific Education and Public Engagement. As a CERCA center and as a Scientific Culture and Innovation Unit accredited by FECYT, it has a strong commitment to bringing research closer to society. As the only research institute in Catalonia with a transversal gender research program, IR Sant Pau serves as a spokesperson for the latest scientific advances. It underscores the importance of conducting research with a gender perspective and promoting the role of women in research and the future of science.

Upcoming Activities in the Second Edition:

• November 22, 2025 – Tibidabo Amusement Park: Mission on the respiratory system
• February 15, 2026 – Grand finale at Tibidabo Amusement Park coinciding with the International Day of Women and Girls in Science

On the occasion of Familial Hypercholesterolemia (FH) Awareness Day, the Sant Pau Research Institute (IR Sant Pau) highlights its commitment to biomedical research aimed at improving the diagnosis and treatment of this highly prevalent genetic disease with a strong impact on cardiovascular health.

Heterozygous familial hypercholesterolemia (FH) is a genetic disorder that affects approximately 1 in 250 people. It is transmitted in an autosomal dominant manner, meaning that inheriting a single altered copy of the gene from one parent is sufficient to develop the disease. It is caused by mutations in key genes of lipid metabolism, such as LDLR, APOB, or PCSK9, which regulate how the body clears LDL cholesterol, commonly known as “bad cholesterol.”

Under normal conditions, the liver removes this cholesterol from the blood and clears it from circulation. This clearance process is essential for maintaining healthy levels. However, in individuals with FH, the clearance mechanism is impaired, leading to excessive LDL cholesterol accumulation in the blood from birth. This buildup significantly increases the risk of developing premature atherosclerotic cardiovascular disease, such as myocardial infarction or angina, at much earlier ages than in the general population—even before the age of forty.

Despite its frequency, FH remains underdiagnosed. It is estimated that fewer than 20% of cases are identified, representing a major missed prevention opportunity. Moreover, even among diagnosed patients, there are wide variations in treatment intensity and adequacy, which negatively impact long-term prognosis.

SAFEHEART: An International Reference Cohort for FH Research

IR Sant Pau actively participates in SAFEHEART, a nationwide, prospective, multicenter cohort in Spain that conducts clinical, lipid, and genetic follow-up of individuals with FH. SAFEHEART was launched in 2004 by the Familial Hypercholesterolemia Foundation, which has since promoted, managed, and coordinated it under the leadership of Dr. Pedro Mata. With more than 4,000 genetically confirmed patients, it is the largest and best-characterized registry of this disease worldwide. Over the years, this cohort has generated numerous reference studies to better understand the natural history of FH and improve clinical management.

One of the most recent studies from this cohort has analyzed in depth the differences between men and women in lifetime burden of atherosclerotic cardiovascular disease. The analysis, involving Dr. Teresa Padró, head of the Cardiovascular Disease Evolution Biomarkers Group at IR Sant Pau and member of the CIBER of Cardiovascular Diseases (CIBERCV), aimed to determine the extent to which sex influences cardiovascular risk. It also sought to determine the age of event onset in people with FH. The results were published in The Lancet Diabetes & Endocrinology.

“Having access to such a well-characterized cohort as SAFEHEART, with over a decade of follow-up and genetically confirmed diagnoses, has allowed us for the first time to robustly analyze how sex influences the cardiovascular prognosis of these patients,” emphasized Dr. Padró.

Women With FH Show Better Clinical Outcomes

The findings are conclusive. Over the follow-up period, women with FH showed a significantly lower risk of cardiovascular events compared to men. Moreover, when these events did occur, they did so at older ages. The mean age of onset of the first cardiovascular event was 61.6 years in women compared with 50.6 years in men. This more than decade-long difference remained even after adjusting for age, family history, traditional risk factors such as hypertension, diabetes, or smoking, as well as lipid profile and type of treatment received.

In terms of event-free survival from major cardiovascular outcomes, such as myocardial infarction, stroke, or coronary revascularization, women also fared better. While the median age of the first event in men was 55.5 years, in women this was delayed until 74.9 years. Thus, the probability of remaining free of cardiovascular disease from birth was considerably higher in the female group.

“Women not only experience fewer cardiovascular events, but these occur later in life. This forces us to reflect on the possible biological bases of this protection and, at the same time, on the biases that still exist in clinical care,” noted Dr. Padró.

Although both men and women achieved similar reductions in LDL cholesterol during follow-up, men more frequently received high-intensity statin combinations with ezetimibe or PCSK9 inhibitors, indicating differences in therapeutic strategies applied according to patient sex. Nevertheless, women with FH in the SAFEHEART cohort showed a lower incidence of coronary disease and lower cardiovascular mortality during follow-up.

These differences may be partly explained by intrinsic biological factors, such as higher HDL cholesterol levels in women, the protective effect of sex hormones before menopause, or lower overall atherosclerotic burden at younger ages.

“The combination of protective biological factors and clinical factors yet to be fully addressed should encourage us to consider more personalized treatment strategies. We cannot assume cardiovascular risk is the same for all patients with FH. Incorporating the sex perspective into clinical practice is essential,” said the IR Sant Pau researcher.

IR Sant Pau Research Drives More Personalized and Equitable Medicine

For years, IR Sant Pau has worked to promote cardiovascular medicine based on risk stratification and personalized clinical decision-making. In the case of FH, this vision involves not only early detection of carriers of pathogenic genetic mutations but also tailoring treatment to each patient’s individual profile, considering clinical, biological, and social characteristics, including sex.

IR Sant Pau’s contribution to the SAFEHEART cohort reinforces the institution’s commitment to translational research that directly impacts clinical practice and public health. Through multidisciplinary teams, collaborative networks, and a comprehensive approach to patient care, the center contributes to advancing knowledge, management, and prognosis of preventable cardiovascular diseases.

“Our goal as researchers is that no patient with FH goes unidentified and untreated. At the same time, we aim to ensure that treatment is the most appropriate for each individual. This is the foundation of medicine that is fairer, more effective, and more humane,” concluded Dr. Padró.

Article Reference:

de Isla LP, Vallejo-Vaz AJ, Watts GF, Muñiz-Grijalvo O, Alonso R, Diaz-Diaz JL, Arroyo-Olivares R, Aguado R, Argueso R, Mauri M, Romero MJ, Álvarez-Baños P, Mañas D, Cepeda JM, Gonzalez-Bustos P, Casañas M, Michan A, Muñoz-Torrero JFS, Faedo C, Barba MA, Dieguez M, de Andrés R, Hernandez AM, Gonzalez-Estrada A, Padró T, Fuentes F, Badimon L, Mata P, SAFEHEART Investigators. Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study. Lancet Diabetes Endocrinol 2024;12:643–52. https://doi.org/10.1016/S2213-8587(24)00192-X

The Sant Pau Research Institute (IR Sant Pau) has been selected in the CaixaImpulse 2025 call by the “la Caixa” Foundation to promote an innovative project in the field of cardiology. This project is led by Dr. Dabit Arzamendi and Dr. Abdel Hakim from Sant Pau Hospital, together with Dr. Oscar Camara from Pompeu Fabra University (UPF).

Procedures such as valve replacement or left atrial appendage closure can cause leaks when implanted devices do not optimally fit the patient’s anatomy. These leaks are serious, as they can lead to heart failure, stroke, or damage to blood cells, with a strong impact on quality of life. Currently available devices are standardized and manufactured in a limited number of sizes, which often prevents a precise fit.

The project proposes a new strategy based on personalized medicine, using advanced 3D modeling and virtual simulations to design custom-made devices tailored to each patient. The methodology involves creating a digital model of the heart, assessing the extent and behavior of the leaks, and developing specific solutions that allow for more effective and lasting sealing. This approach is expected to reduce risks such as clot formation, avoid repeated interventions, and improve recovery.

In an initial phase, the team will validate the devices through simulations and imaging techniques, with the goal of optimizing the designs and demonstrating their effectiveness under realistic conditions. The ultimate purpose is to improve clinical outcomes and provide greater quality of life for patients with complications following the implantation of cardiac devices.

According to Dr. Dabit Arzamendi, “Our goal is to bring truly personalized solutions into the clinical setting that respond to each patient’s anatomy. We believe this approach will reduce serious complications and significantly improve recovery and quality of life for affected individuals.”

CaixaImpulse 2025: Biomedical Innovation With Impact

The CaixaImpulse 2025 call aims to accelerate the arrival of innovations in biomedicine and health to the market, supporting projects that address unmet clinical needs and fostering the creation of science-based products, services, and companies.

In this edition, the “la Caixa” Foundation has allocated €3.8 million to promote 31 biomedical projects from research centers, hospitals, and universities in Spain and Portugal. The call received a total of 428 applications, evaluated by international panels of experts in health innovation.

The selected projects are distributed across different areas: 14 in the field of therapies, 12 in medical devices, 4 in diagnostics, and 1 in digital health. Depending on their level of maturity, initiatives receive funding ranging from €50,000 to €500,000 and can advance to later phases as they reach development milestones.

In addition to financial support, CaixaImpulse offers participating teams specialized training, mentorship, and expert guidance in key areas such as technology transfer, intellectual property, exploitation strategies, and access to investors.

Since its launch in 2015, CaixaImpulse has supported 263 projects, contributed to the creation of 54 spin-offs, and helped raise more than €180 million in additional funding from investors and competitive calls.

The approval of new antibody-based drugs for Alzheimer’s disease—lecanemab and donanemab—and of blood-based diagnostic tests marks the beginning of a new era in the diagnosis and treatment of this condition. However, without swift reforms in healthcare systems, public policies, and social attitudes, their full potential will not be realized, warn 40 leading Alzheimer’s experts in The Lancet Series on Alzheimer’s disease.

Alzheimer’s disease accounts for approximately 70% of all dementia cases and is one of the leading causes of disability, resulting in high social and economic costs.

In a novel comparison, the series highlights that new monoclonal antibody treatments can slow the progression of Alzheimer’s disease to a level comparable with the effectiveness of drugs used in cancer, rheumatoid arthritis, and multiple sclerosis. Nonetheless, the authors note that differences in patient age, clinical outcomes, and side effects mean these comparisons must be interpreted with caution.

Despite the similarity in treatment effectiveness for other diseases, the high costs of the drugs, the complex requirements of diagnostic testing, suboptimal attention to behavioral symptoms, and insufficient resources threaten to leave Alzheimer’s patients behind.

Encouragingly, improvements in Alzheimer’s disease prevention are also on the horizon, with the emergence of Brain Health Services, which identify people at high risk of developing the disease and provide them with personalized treatment programs. However, most Alzheimer’s cases occur in individuals at low or normal risk, making population-level measures that reduce risk—such as healthier urban design and restrictions on alcohol and sugary drinks—essential.

The authors call for coordinated global action to ensure that rapid scientific progress in the field of Alzheimer’s disease is matched by reforms in healthcare provision, policies, and society.

Among the series’ authors are two Spanish researchers: Dr. Juan Fortea, from the Sant Pau Research Institute (IR Sant Pau) and head of the Sant Pau Memory Unit, and Dr. Eider Arenaza-Urquijo, from ISGlobal. Both contributed to the section on diagnosis, a field currently undergoing a true revolution thanks to the arrival of blood biomarkers. These tests make it possible to detect biological changes of Alzheimer’s even before the first clinical symptoms appear, opening the door to interventions at very early stages of the disease and maximizing the impact of new treatments.

In Dr. Fortea’s words, “We are witnessing a milestone in the treatment of Alzheimer’s with the first drugs capable of modifying the course of the disease. This breakthrough makes continued progress in diagnosis even more significant and important, especially with the development of biomarkers that allow us to identify patients in the earliest stages. Only then can we ensure that new treatments are administered at the right time and have the greatest possible benefit for patients.”

The lead author of the series, Professor Giovanni Frisoni from the University of Geneva (Switzerland), states, “Blood tests, biological drugs for Alzheimer’s disease, and preventive interventions are shifting care into an entirely new and exciting landscape. However, patients’ longstanding needs will not disappear. On the contrary, more primary care physicians and dementia specialists will need to master the less flashy but steady advances made over recent decades in the care and treatment of behavioral disorders. This includes the use of sophisticated imaging and laboratory diagnostic tools, and psychosocial care. A concerted societal effort in this direction will ensure that our current and future patients fully benefit from the potential of scientific and technological advances.”

To access the articles, visit:

https://www.thelancet.com/series-do/alzheimers-disease

Cancer continues to be one of the leading causes of death worldwide and in Spain. According to the report Cancer Figures in Spain 2025 by the Spanish Society of Medical Oncology (SEOM), nearly 300,000 new cases of cancer will be diagnosed in Spain this year, with colorectal, breast, lung, prostate, bladder, lymphoma, and myeloma being the most common. In 2023, tumors accounted for more than a quarter of all deaths in Spain (26.5%), with 115,889 deaths, placing them practically at the same level as cardiovascular diseases as the leading cause of mortality.

Despite these figures, research has enabled survival to improve significantly. Five-year net survival now reaches 55.3% in men and 61.7% in women, nearly double the rate of four decades ago. These advances are due both to earlier diagnosis—which allows treatment of the disease in its initial stages—and to the development of increasingly effective and personalized therapies.

Immunotherapy and CAR-T Therapies: A New Horizon

Among the most innovative treatments that have transformed cancer care is immunotherapy, which harnesses the patient’s immune system to recognize and destroy tumor cells. One of the most promising modalities is CAR-T therapy, which genetically modifies the patient’s T lymphocytes to specifically and more effectively target and eliminate tumor cells.

The Sant Pau Research Institute (IR Sant Pau) is one of the few centers in Europe to develop, academically and independently—without pharmaceutical industry support—two CAR-T therapies:

• HSP-CAR19M, directed at B-cell lymphomas via the CD19 antigen, including diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. It is enriched with memory T cells to ensure durability and is being developed within the TERAV network of the Instituto de Salud Carlos III.
• HSP-CAR30, targeting the CD30 antigen, focused on classical Hodgkin lymphoma and other CD30⁺ tumors. It is the first academic European CAR-T therapy against this target, also designed with memory T cells to reinforce efficacy and persistence.

The most recent major achievement in this line of research has been the highly positive results in patients with refractory Hodgkin lymphoma treated with HSP-CAR30. These patients had already undergone multiple lines of unsuccessful treatment, placing them in a very difficult clinical situation with few therapeutic alternatives. In this context, the new academic HSP-CAR30 therapy developed at IR Sant Pau has achieved high rates of long-lasting responses, with patients remaining disease-free for more than three years. This confirms the potential of second-generation CAR-T therapies designed at the same center.

In the Phase I clinical trial, all patients treated responded to therapy. Moreover, half achieved complete remission, meaning the disease completely disappeared in imaging studies and follow-up clinical analyses. Another relevant finding is that these responses have been sustained over time in a large proportion of cases, demonstrating that the therapy is not only effective in the short term but also capable of inducing long-term disease control. Phase II of the trial, the only one of its kind in Europe, will conclude this October, marking a milestone in the history of CAR-T therapy.

Dr. Javier Briones, head of the Cellular Immunotherapy and Gene Therapy Group at IR Sant Pau and the Hematology Service at Sant Pau Hospital, who is responsible for developing these therapies, emphasized, “The high overall response rate is very uncommon in patients who have undergone multiple lines of treatment. Moreover, 50% achieved complete remission, with the disease disappearing in imaging studies and clinical analyses. This is crucial because it demonstrates that the persistence of CAR-T cells has a real and sustained effect on the disease, which is precisely what we seek.”

The CXCR4 Receptor: A Key Target Against Metastasis

Cancer research at IR Sant Pau is not limited to CAR-T therapies. Another major strategic focus of the institute is the study of the CXCR4 receptor, a protein that plays a fundamental role in tumor progression. Numerous studies have shown that its overexpression is associated with a greater ability of malignant cells to invade and spread, making it a true “Achilles’ heel” in multiple types of cancer.

The Oncogenesis and Antitumor Drugs Group, led by Dr. Ramon Mangues, has been researching CXCR4 for more than fifteen years. It has developed a unique nanomedicine platform capable of selectively directing therapeutic agents against tumor cells that express high levels of this receptor. These protein–drug nanoconjugates release their cytotoxic payload only in such cells, reducing adverse effects on healthy tissues.

In preclinical models, these nanoconjugates have shown high efficacy in both solid and hematologic tumors. In particular, a CXCR4-targeted nanotoxin was able to slow colorectal cancer growth and activate the patient’s immune response, opening possibilities for combinations with immunotherapy. In addition, the group has contributed to an international review on innovative therapies targeting CXCR4, positioning Sant Pau as an emerging reference in anti-metastatic treatments.

The strength of this research line has allowed the technology developed at Sant Pau to be transferred to the business sector through Nanoligent, a joint spin-off of the UAB and IR Sant Pau itself. The company, co-founded by Dr. Mangues, is currently focusing its efforts on the clinical development of CXCR4-targeted nanoconjugates, with the goal of making them available to patients in the coming years. This step reflects the institute’s commitment to translational innovation and collaboration with the biotechnology sector to accelerate the arrival of new treatments to the healthcare system.

Dr. Ramon Mangues stressed, “Metastasis remains the leading cause of cancer-related death, and CXCR4 is key in this process. Targeting it precisely allows us to selectively destroy the most aggressive cells while reducing toxicity. Our experience places us in a unique position to move forward toward anti-metastatic therapies with clinical potential in the coming years.”

Cancer Research Expands at Sant Pau

IR Sant Pau’s commitment to cancer research is also reflected in the creation of new specialized groups. One of them is the TRAIL Group (Thoracic Surgery Research and Innovation in Lung Cancer), led by Dr. Juan Carlos Trujillo-Reyes, which focuses its work on lung cancer, the leading cause of cancer death worldwide. Its research lines range from early diagnosis through screening programs to improving surgical techniques, with a special emphasis on robotic surgery, as well as integrating molecular and clinical biomarkers into clinical practice.

Another newly created group is the Gynecological and Breast Pathologies Group, coordinated by Dr. Silvia Cabrera Daz. This group focuses its research on gynecological neoplasms—endometrium, ovary, uterus, vulva, vagina, and breast—as well as benign pathologies with major impact on women’s quality of life, such as endometriosis, fibroids, and chronic pelvic pain. With a multidisciplinary approach, the group combines clinical care, teaching, and research, with the goal of generating cutting-edge knowledge and improving women’s healthcare in a highly complex hospital setting.

An international group of experts, including Dr. Saül Martínez-Horta, researcher at the Sant Pau Research Institute (IR Sant Pau) and neuropsychologist at the Movement Disorders Unit of Hospital Sant Pau, has published in the journal Movement Disorders a scientific review that thoroughly analyzes the most widely used neuropsychological tools to assess attention, working memory, and executive functions in Parkinson’s disease. The work, promoted by the International Parkinson and Movement Disorder Society (MDS), provides clear recommendations on which instruments should be used for a more accurate evaluation of the cognitive status of these patients, both in clinical practice and in research.

The evaluation of these cognitive functions is key because their deterioration is one of the most common non-motor complications in Parkinson’s disease. It can appear in very early stages, even before motor symptoms, and is associated with a progressive loss of autonomy and quality of life. However, the great variety of existing tests, differences in their psychometric quality, and the lack of unified criteria have so far hindered consistent assessment. According to Dr. Martínez-Horta, “It is not enough to use any test available; we need instruments with a solid scientific basis, adapted to the clinical reality of the Parkinson’s patient, and that allow us to detect subtle but significant changes.”

Eight Tests With the Highest Guarantees

The review assessed a total of 30 instruments and concluded that 8 of them offer the best guarantees of reliability, validity, and clinical applicability. Four focus mainly on attention and working memory: three subtests of the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV)—Digit Span, which measures immediate memory and the ability to manipulate information; Coding, which evaluates processing speed and visuomotor coordination; and Symbol Search, which examines speed in visual discrimination and concentration—as well as the Trail Making Test, which analyzes processing speed, mental flexibility, and visual search. The WAIS-IV is one of the most widely used scales internationally to measure cognitive abilities, and its subtests provide results that can be compared with large normative datasets.

The other four recommended tests are oriented toward executive functions: Similarities, another WAIS-IV subtest that explores abstract verbal reasoning; the Wisconsin Card Sorting Test, considered the benchmark for evaluating cognitive flexibility and the ability to adapt to new rules; the Verbal Fluency Tests, which measure the ability to generate words according to phonemic or semantic criteria; and the Stroop Color-Word Test, in its abbreviated Victoria version, which evaluates the inhibition of automatic responses and adaptation to changing conditions. As Dr. Martínez-Horta points out, “These tools have not only proven to be reliable and valid, but they are also sensitive to changes that occur during the disease and to the effects of certain treatments.”

From Theory to Clinical Practice

For the authors, having this classification has an immediate impact on clinical practice, as it provides professionals with a clear guide to making informed decisions. Dr. Martínez-Horta emphasizes that “In the clinic, choosing the right test can make the difference between detecting an early cognitive change or overlooking it.” This is especially relevant in Parkinson’s disease, where cognitive changes may be subtle in the early stages and go unnoticed if tools with sufficient sensitivity are not used.

The review also highlights that the selection of the test should be adapted not only to the purpose of the evaluation—early detection, long-term monitoring, or assessing the effect of therapies—but also to the characteristics and limitations of the patient. Factors such as educational level, emotional state, fatigue, or motor fluctuations can influence performance and, therefore, the interpretation of results. “If a patient presents motor impairment that makes writing or manual speed difficult, a test requiring these skills could show low performance not because of a real cognitive deficit, but because of interference from motor symptoms,” the researcher explains. In such cases, the recommendation is to prioritize verbally administered or adapted tools that minimize the impact of these limitations.

The paper stresses that using standardized, evidence-based tests improves diagnostic accuracy and promotes homogeneity in research, making it easier to compare results across different centers and studies. This, in turn, helps advance knowledge of the disease and develop more effective interventions to preserve cognitive function.

An International Reference Framework

The review establishes which tests are the benchmarks and identifies those that, despite their common use, have limitations and require further research to confirm their utility. The analysis indicates that some widely used instruments lack normative studies specific to the Parkinson’s population or present reliability issues when applied in real-world clinical contexts. In such cases, the expert group recommends cautious use, always combined with complementary measures.

For Dr. Martínez-Horta, this work represents “an important step toward standardizing cognitive evaluation in Parkinson’s disease on a global scale.” The researcher stresses that “We want this guide to serve as a tool to unify criteria and improve the quality of cognitive evaluations in Parkinson’s disease worldwide.” Having an international reference framework allows data obtained in different countries and centers to be comparable, which is essential for establishing progression patterns, identifying risk factors, and evaluating the impact of new treatments.

In addition, homogeneity in the choice of tools will make it possible to integrate large international databases, fostering collaborative studies with larger and more representative samples. “Homogeneity in evaluation is key to advancing research, comparing data between centers, and ultimately offering better care to patients,” he concludes. The ultimate goal, as the author group highlights, is for this consensus to translate into more precise evaluations, earlier diagnoses, and more effective intervention strategies.

Reference Article:

Biundo R, Bezdicek O, Cammisuli DM, Cholerton B, Dalrymple-Alford JC, Edelstyn N, Fiorenzato E, Holker E, Martinez-Horta S, Martini A, Santangelo G, Segura B, Siri C, Tröster A, Mestre TA, Ferro ÁS, Hyczy de Siqueira Tosin M, Skorvanek M, Weintraub D, Geurtsen GJ, and the members of the MDS Clinical Outcome Assessment Scientific Evaluation Committee. Attention/working memory and executive function in Parkinson’s disease: Review, critique, and recommendations. Mov Disord 2025. https://doi.org/10.1002/mds.30293

A review article published in Nature Reviews Neurology, whose first author is Dr. Marta Caballero from the team of Dr. Luis Querol, member of the Neuromuscular Diseases Group at the Sant Pau Research Institute (IR Sant Pau), analyzes recent advances in the diagnosis and treatment of primary autoimmune neuropathies—a group of rare and debilitating disorders of the peripheral nervous system that includes Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

For more than three decades, the therapeutic approach to these disorders has relied on nonspecific strategies such as intravenous immunoglobulin, corticosteroids, or plasma exchange. Although these have improved the prognosis for many patients, their effectiveness is limited, and not everyone responds in the same way. Moreover, these therapies do not target the specific mechanisms that trigger the disease.

A New Direction

The review article explains how, lately, research has enabled a qualitative leap in this field. One of the most significant advances is the identification of autoantibodies directed against essential proteins at the nodes of Ranvier—structures critical for the transmission of nerve impulses. This finding, in which the Neuromuscular Diseases Unit at Sant Pau Hospital has played a leading role, led to the recognition of a new diagnostic category: autoimmune nodopathies. These are neuropathies in which the immune system specifically attacks these regions of the nerve fiber, disrupting communication between neurons and causing weakness and loss of sensation.

This new concept helps explain the clinical heterogeneity of some patients and opens the door to more targeted treatments. At the same time, the diagnostic criteria for GBS and CIDP have been redefined, enabling more accurate detection of disease, reducing misclassification, and better guiding therapeutic decisions.

The article coordinated by Dr. Querol also reviews targeted therapies that are beginning to reach clinical practice. A notable example is efgartigimod, recently approved in Europe and the United States as the first specific treatment for CIDP. This drug lowers the levels of pathogenic antibodies in the blood and represents a paradigm shift after more than 30 years without therapeutic innovations of this magnitude. In addition, clinical trials are underway with complement inhibitors, which have shown promising results not only in CIDP but also in GBS and multifocal motor neuropathy.

Another key aspect is biomarkers, which provide objective information about disease activity and progression. Among the most promising are serum neurofilament light chain, which reflects axonal damage, as well as specific autoantibodies and proteins unique to peripheral nerves, such as peripherin or periaxin. Validating these biomarkers will not only allow earlier diagnosis but also help predict treatment response and personalize patient follow-up.

A Transformation in Patient Care

“The field of autoimmune neuropathies is undergoing a true transformation,” explains Dr. Marta Caballero. “We are moving from general therapies to strategies that target the exact mechanisms causing the disease. This means we will be able to be much more precise, reduce treatment toxicity, and improve patients’ quality of life.”

Dr. Querol, for his part, emphasizes the importance of the new biomarkers. “Thanks to these tools, we will not only be able to diagnose more quickly and reliably, but also to monitor disease progression and treatment response in an objective way. This is an essential step toward advancing personalized medicine in this field.”

The advances summarized in this review place primary autoimmune neuropathies—until now considered orphan diseases in terms of innovation—at the center of a paradigm shift. More profound understanding of their mechanisms, the availability of more rigorous diagnostic criteria, the arrival of new targeted therapies. The development of reliable biomarkers will allow patients to receive care that is more effective, safer, and tailored to their individual needs.

Reference Article:

Caballero-Ávila M, Pascual-Goñi E, Lleixà C, Martín-Aguilar L, Collet-Vidiella R, Querol L. The changing landscape of primary autoimmune neuropathies. Nat Rev Neurol 2025. https://doi.org/10.1038/s41582-025-01133-3

During September and October, My Alma, a brand specialized in intimate and menstrual wellness products, is launching a solidarity campaign to support ovarian cancer research at the Sant Pau Research Institute.

For every product sold through its online store, My Alma will donate a solidarity round-up, which will become a direct contribution to fund a pioneering project at our center.

A company committed to women’s health

My Alma was created with the mission of placing women’s health at the center, offering more sustainable, healthy, and body- and environmentally-friendly products. Inspired by her own personal experience, its founder also wanted the brand to become a driver of social change, raising awareness and providing resources for medical research that directly affects women.

Supporting ovarian cancer research

The funds raised will go to an innovative project at the Sant Pau Research Institute that studies how signals from the nervous system can influence the growth and spread of tumors. The goal is to find new strategies to tackle ovarian cancer that is resistant to current treatments and to offer new hope to patients.

Raising awareness to break taboos

As part of this collaboration, My Alma and Sant Pau will also publish a series of educational video capsules, created by Sant Pau professionals, on topics related to menstruation. The aim is to provide rigorous information, promote women’s health, and help break down taboos that are still present in society.

A collaboration with impact

Through this initiative, My Alma and the Sant Pau Research Institute are joining forces to advance research and improve the lives of women living with this disease, while also promoting awareness and health education.

The Sant Pau Research Institute (IR Sant Pau) has approved the creation of the new research group TRAIL (Thoracic Surgery Research and Innovation in Lung Cancer), dedicated to advancing research and innovation in the field of thoracic surgery and lung cancer. The group will be led by Dr. Juan Carlos Trujillo-Reyes, head of the Joint Thoracic Surgery Service of Sant Pau and del Mar hospitals. The founding members of the new group, in addition to Dr. Trujillo, are Dr. Elisabeth Martínez, a specialist in minimally invasive techniques and in improving patients’ quality of life, and Dr. Josep Belda Sanchis, a thoracic surgeon with more than thirty years of experience in complex lung surgery and oncological pathology.

According to Dr. Trujillo, “Lung cancer remains the leading cause of cancer mortality worldwide and in Spain. That is why it is essential to commit to research and innovation in early diagnosis and advanced surgical techniques that allow us to improve outcomes and patient survival.”

TRAIL was established with the goal of consolidating high-quality research with a real impact on clinical practice. It is a pioneering and distinctive initiative within the national landscape, standing out for its innovative character and the uniqueness of its proposal in the current research context. Its main lines of research include early diagnosis of lung cancer through screening programs and advanced imaging techniques; optimal surgical selection after induction treatments; improvement of surgical techniques and perioperative outcomes, with a special focus on robotic surgery and prehabilitation programs; and translational research on biomarkers to integrate molecular and clinical data into therapeutic decision-making.

“Sant Pau offers us a privileged environment to develop high-level research, thanks to multidisciplinary collaboration and a direct connection with clinical practice. This synergy is key to generating knowledge that has an immediate impact on patients,” says Dr. Trujillo.

Dr. Juan Carlos Trujillo earned his degree in medicine and surgery from the Autonomous University of Barcelona (2009) and his PhD in medicine from the same university (2022). A specialist in thoracic surgery, he has worked at Sant Pau since 2015 and has been one of the main drivers of minimally invasive surgery at the center. He combines his clinical activity with teaching as an associate professor at the Autonomous University of Barcelona (UAB) and with an outstanding research career, with more than 60 publications in high-impact journals.

He has played a key role in the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), where he coordinated the Thoracic Oncology Area and the CASSANDRA project, the first nationwide pilot study on lung cancer screening. Furthermore, he currently coordinates SEPAR’s research and development projects in thoracic oncology and is co-director of the national thymic tumor database. In 2024, he received SEPAR’s Young Investigator of the Year Award.

According to Dr. Trujillo, “The creation of the TRAIL group allows us to structure and strengthen all the work we are already doing in research and innovation in thoracic surgery and lung cancer. Our goal is to generate useful knowledge that translates into better patient care and reduced mortality from this disease.”

With its creation, TRAIL aims to consolidate Sant Pau as a reference center for research and innovation in thoracic surgery and lung cancer, promoting multidisciplinary synergies and training new generations of professionals in the biomedical field.

Springer Nature has just published the Atlas of Virtual Surgical Planning and 3D Printing for Cranio-Maxillo-Facial Surgery, an internationally recognized reference work that marks a milestone in the integration of technological innovation and the humanization of healthcare in the field of cranio-maxillofacial surgery. The book was edited by Dr. Alessandro Tel, a specialist in maxillofacial surgery at the Department of Head and Neck Surgery and Neurosciences at the University Hospital of Udine (Italy), and Dr. Massimo Robiony, Associate Professor of Maxillofacial Surgery at the University of Udine and Head of the Maxillofacial Surgery Unit at the University Hospital of Udine.

Technology and Humanization: A Surgical Alliance

The atlas is the result of years of work and collaboration among professionals from around the world who share a common vision: medicine as a constantly evolving science, with the human being as the priority. The editors call this approach Techno-Humanization, meaning the application of the full potential of technology—including artificial intelligence—to clinical practice, while always respecting ethics and reinforcing the human dimension of medical care.

In the specific field of head and neck surgery, virtual reality, 3D surgical planning, and biomodel printing have become essential tools for improving safety, precision, and communication with the patient. This atlas is intended to serve as both a didactic and practical guide to their advanced use.

Imaging Protocols for More Precise Surgery

One of the contributing authors is Dr. Josep Munuera, head of the Advanced Medical Imaging, Artificial Intelligence, and Image-Guided Therapy group at the Sant Pau Research Institute (IR Sant Pau), and Head of the Diagnostic Imaging Department at Hospital Sant Pau. His contribution focuses on the chapter dedicated to specific image acquisition protocols in radiology for virtual surgical planning and 3D printing in cranio-maxillofacial surgery. This section provides an in-depth review of the techniques, parameters, and considerations necessary to obtain images of the highest diagnostic and surgical quality.

As Dr. Munuera explains, “A proper choice of imaging technique and the correct configuration of acquisition parameters is the foundation that allows the surgeon to plan the surgery with total safety and precision.” He adds, “Teamwork between radiologists and surgeons is key: our decisions during the diagnostic phase directly determine the degree of precision and the outcome of the procedure.”

From Diagnostic Imaging to Surgical Precision

The chapter describes how medical imaging has evolved from X-rays and the introduction of CT scans and magnetic resonance imaging (MRI) to the current integration of artificial intelligence, 3D reconstruction, and additive manufacturing. These technologies not only enable realistic visualization of complex anatomical structures but also fuse data from different modalities to plan more personalized and safer procedures.

In cranio-maxillofacial surgery, where bone and soft tissue structures coexist in a small and delicate anatomical space, correct selection and configuration of the imaging technique—whether CT, CBCT, MRI, ultrasound, or optical scanning—is critical for surgical success. Each modality offers advantages and limitations: CT provides high spatial resolution for bone, MRI is irreplaceable for nerves, vessels, and soft tissues, CBCT stands out for its low radiation and high bone resolution, and 3D photogrammetry or intraoral scanning allow precise capture of the facial surface and dentition for integration into the surgical model.

The chapter also discusses the use of intraoperative imaging—such as CT or CBCT in the operating room, ultrasound, or fluorescence techniques—to verify in real time the placement of implants, facial symmetry, or flap perfusion. A substantial section is devoted to acquisition parameters adapted to each clinical indication, from fractures and tumors to congenital anomalies and joint pathology, as well as to advanced MRI sequences to obtain isotropic volumetric models.

3D reconstruction and segmentation play a central role, with methods that allow the isolation of bones, vessels, and soft tissues using semi-automatic algorithms or intelligent delineation tools, always prioritizing the quality of the original data. Dr. Munuera emphasizes that “standardizing protocols and minimizing artifacts are essential, as is aligning the acquisition with the surgery date to ensure maximum anatomical correspondence.”

The chapter also includes specific considerations for pediatric patients, prioritizing reduced radiation exposure, the use of non-ionizing techniques, and the creation of child-friendly environments to support cooperation. Finally, it introduces a rarely addressed topic in technical texts: the environmental impact of medical imaging. From the energy consumption of equipment to the management of electronic waste and the use of rare metals and contrast agents, the text calls for the adoption of more efficient technologies, recycling programs, and sustainable solutions that reduce the ecological footprint of the sector.

This atlas offers a tool that combines technical rigor, ethical awareness, and forward-looking vision, with the aim of ensuring that the most advanced technology is always at the service of surgical precision and the humanization of patient care. In the words of Dr. Munuera, “It is an honor to have contributed to a work that brings together top-level technical knowledge and conveys a work philosophy in which technology is a means to better care for people.”

Reference:

Tel A, Robiony M, editors. Atlas of Virtual Surgical Planning and 3D Printing for Cranio-Maxillo-Facial Surgery. Cham: Springer Nature; 2025.

A study led by the Sant Pau Research Institute (IR Sant Pau), the Clinical Biochemistry Service at Hospital de Sant Pau, and the Spanish Biomedical Research Network in Diabetes and Associated Metabolic Diseases (CIBERDEM) has identified a key disruption in cholesterol transport to the brain in patients with Alzheimer’s disease. The findings suggest that the lipoproteins in the cerebrospinal fluid of patients with Alzheimer’s have a reduced ability to deliver cholesterol to neurons. This impairment may be linked to the presence of the APOE4 genetic variant, one of the main known risk factors for the disease. The study has been published in the Journal of Lipid Research.

According to Dr. Mireia Tondo, researcher in the Lipid Disorder Pathophysiology Group at IR Sant Pau and lead author of the project, “We’ve long known that people with the APOE4 variant—especially in the homozygous form—have a much higher risk of developing Alzheimer’s, but until now, the reasons for this weren’t well understood. Our study suggests that one contributing factor may be that neurons, in the presence of this variant, have a harder time absorbing cholesterol delivered through the cerebrospinal fluid.”

Cholesterol: Essential for Neuronal Viability

Cholesterol is a vital molecule for proper neuronal function. It plays a key role in membrane formation, synaptic transmission, and myelin production. Unlike other organs, the brain does not receive cholesterol from the bloodstream due to the protective blood–brain barrier. “All the cholesterol the brain needs is produced locally,” explains Dr. Tondo, “and it’s stored in specific lipoprotein particles that transport it from glial cells to neurons. If this process fails, the neuron may not receive the structural and functional resources it needs.”

The research team analyzed cerebrospinal fluid samples from 10 patients with Alzheimer’s disease and 10 individuals without the disease, all part of the Sant Pau Initiative on Neurodegeneration (SPIN) cohort. They evaluated two stages of cerebral lipid transport: first, the ability of astrocytes to release cholesterol into the cerebrospinal fluid, and second, the ability of neurons to absorb this cholesterol. The results indicated that astrocyte cholesterol release was similar in all participants, but neuronal uptake was clearly impaired in patients with Alzheimer’s.

Based on these findings, the team sought to determine whether this defect was related to genetics. “Most of the patients in our sample were heterozygous for the APOE4 variant, and we observed lower cholesterol uptake in them. So we decided to go further and create recombinant lipoprotein nanoparticles, identical except for containing either APOE3 or APOE4,” Dr. Tondo explains. “When we tested them in cultured neurons, those containing APOE4 delivered cholesterol much less efficiently. This led us to believe that this variant may directly contribute to the dysfunction we observed.”

Protein Alterations and Functional Implications

The researchers also performed a detailed proteomic analysis of the cerebrospinal fluid lipoproteins. They identified 239 proteins associated with these particles, of which 27 were altered in Alzheimer’s patients. Interestingly, none of these differences directly involved proteins related to cholesterol metabolism. “This finding tells us that the lipoprotein system is far more complex than we thought, and that other mechanisms—such as inflammation, cell adhesion, or protein degradation—may also influence disease progression,” adds Dr. Tondo.

“Efficient delivery of cholesterol to neurons is essential for their function and maintenance. Our results strongly suggest that this process is impaired in Alzheimer’s disease, particularly in the presence of the APOE4 variant,” says Carla Borràs, the study’s first author. “This may contribute to neuronal vulnerability and progressive degeneration.”

This research was made possible through collaboration between the lipid metabolism group and the Memory Unit at Sant Pau, an international reference center in the clinical and biomolecular study of dementias. Additional contributors included researchers from the Spanish Biomedical Research Network in Neurodegenerative Diseases (CIBERNED), the Spanish National Center for Cardiovascular Research (CNIC), the Biomedical Research Network in Cardiovascular Diseases (CIBERCV), and the Catalan Institute of Nanoscience and Nanotechnology (ICN2).

Dr. Tondo stresses the importance of cautious interpretation: “This study does not prove that cholesterol deficiency is the direct cause of the disease, but it may be one of the factors contributing to neuronal damage. In any case, it opens a very interesting line of research into cerebral lipid metabolism, especially in people with genetic risk.”

The research group is already working on a new study to see whether this mechanism is also impaired in people with Down syndrome, a population with genetic risk for developing Alzheimer’s. “We want to know whether the problem with neuronal cholesterol uptake also exists in this other genetic context. This could help us understand whether there are common mechanisms and whether improving lipid metabolism could be a way to delay neurodegeneration,” concludes Dr. Tondo.

Project Funding

This work was partially funded by the Instituto de Salud Carlos III (ISCIII), part of the Spanish Ministry of Economic Affairs and Digital Transformation, and by the European Regional Development Fund (FEDER) under the slogan “A way of making Europe,” through projects PI21/00140, PI23/00232, PI18/0035, PI22/00758, JR22/00003, INT21/00073, PI20/01473, and PI23/01786.

The study was also funded by the U.S. National Institutes of Health (NIH) through grants R01 AG056850, R21 AG056974, R01 AG061566, R01 AG081394, and R61 AG066543, as well as by the Tatiana Pérez de Guzmán el Bueno Foundation through grant IIBSP-DOW-2020-151, and the European Union’s Horizon 2020 Research and Innovation Framework Programme (H2020-SC1-BHC-2018-2020).

Article reference:

Borràs C, Canyelles M, Santos D, Rotllan N, Núñez E, Vázquez J, Maspoch D, Cano-Sarabia M, Zhao Q, Carmona-Iragui M, Sirisi S, Lleó A, Fortea J, Alcolea D, Blanco-Vaca F, Escolà-Gil JC, Tondo M. Cerebrospinal fluid lipoprotein-mediated cholesterol delivery to neurons is impaired in Alzheimer’s disease and involves APOE4. J Lipid Res 2025:100865. https://doi.org/10.1016/j.jlr.2025.100865

Lipoprotein(a), also known as Lp(a), is a lipid particle with pro-inflammatory properties whose blood concentration is determined mainly by genetic factors. Its involvement in the development of atherosclerotic cardiovascular disease is well documented, but one key question remains in the field of primary prevention: Does Lp(a) also pose a relevant risk in people without classic cardiovascular risk factors?

To address this question, a large international study published in the European Journal of Preventive Cardiology analyzed data from 66,495 individuals across eight European population cohorts, followed over a median of 9.7 years. All participants were free of coronary heart disease at the time of enrollment. The study included the participation of Dr. Teresa Padró, researcher in the Biomarkers of Cardiovascular Disease group at the Sant Pau Research Institute (IR Sant Pau) and member of CIBERCV.

Researchers stratified participants based on the number of modifiable cardiovascular risk factors they had at the start of the study: high blood pressure, diabetes mellitus, hypercholesterolemia, and smoking. A total of 41,770 individuals had none or only one of these risk factors, while 24,725 had two or more. Participants were also classified by their Lp(a) levels, using the 90th percentile of the distribution (43.2 mg/dL) as the cutoff.

Over the follow-up period, a total of 3,467 new cases of ischemic heart disease were recorded among the participants. This category includes myocardial infarction, coronary death, unstable angina, coronary revascularization procedures, and deaths of undetermined cause but with a possible cardiac origin. Of these, 1,191 occurred in individuals who, at the start of the study, had no cardiovascular risk factors or only one. The remaining 2,276 cases occurred in participants with two or more traditional risk factors.

What About Lp(a)?

The study results show that having elevated Lp(a) levels —above 43.2 mg/dL, which corresponds to the top 10% of the population—increases the risk of developing coronary heart disease, such as a heart attack, in both people with few cardiovascular risk factors and those with several. In fact, the increased risk was very similar in both groups: 38% higher in those with none or only one risk factor and 27% higher in those with two or more. This difference was not statistically significant, meaning that the impact of high Lp(a) on coronary risk is essentially the same, regardless of a person’s prior risk profile.

“This study indicates that people with elevated Lp(a) levels are at increased risk of coronary heart disease even if they don’t have high blood pressure, diabetes, high cholesterol, or a history of smoking,” explains Dr. Teresa Padró. “This poses a significant clinical challenge, since traditional prevention strategies based on risk factor reduction don’t apply in these cases.”

Currently, there are no approved treatments specifically designed to lower Lp(a) levels, although many clinical trials are underway. According to the authors, until these drugs become available, the only option to mitigate the cardiovascular risk associated with Lp(a) remains intensive control of modifiable risk factors—a strategy that is not feasible in individuals who do not have any.

“These findings also reinforce the need to develop therapies that target Lp(a) in the context of primary prevention,” adds Dr. Padró. “They also highlight the importance of including Lp(a) in cardiovascular risk assessment, even in people who appear to be healthy.”

The study is part of the BiomarCaRE project (Biomarker for Cardiovascular Risk Assessment across Europe), funded by the European Union through the Seventh Framework Programme (FP7/2007–2013). Lp(a) levels were measured in a central laboratory using a standardized immunoturbidimetric method, ensuring the reliability of the data analyzed.

Reference Article:

Arnold N, Goßling A, Bay B, Weimann J, Blaum C, Brunner FJ, Ferrario MM, Brambilla P, Cesana G, Leoni V, Palmieri L, Donfrancesco C, Padró T, Andersson J, Jousilahti P, Ojeda F, Zeller T, Linneberg A, Söderberg S, Iacoviello L, Gianfagna F, Sans S, Veronesi G, Thorand B, Peters A, Tunstall-Pedoe H, Kee F, Salomaa V, Schnabel RB, Kuulasmaa K, Blankenberg S, Waldeyer C, Koenig W. Lipoprotein (a) and incident coronary heart disease in the community: Impact of traditional cardiovascular risk factors. Eur J Prev Cardiol 2025. https://doi.org/10.1093/eurjpc/zwaf340

A team led by Drs. Elba Pascual-Goñi and Luis Querol, researchers from the Neuromuscular Diseases Group at the Sant Pau Research Institute (IR Sant Pau), has published in the journal Journal of NeuroEngineering and Rehabilitation the results of a study validating the use of digital biomechanical sensors to assess gait in people with peripheral neuropathies. The study was carried out in collaboration with the startup Ephion Health and showed that this technology can provide objective, sensitive, and repeatable measurements of patients’ functional status.

Gait assessment is a fundamental tool for understanding the functional impact of peripheral neuropathies, a group of diseases that affect the nerves connecting the central nervous system to the limbs. These impairments can cause muscle weakness, imbalance, instability, and difficulty walking, with a direct impact on patients’ quality of life. However, the clinical evaluation of these changes is often based on subjective scales that may not capture the most subtle or early changes.

Wearable Technology to Identify Abnormal Gait Patterns

The study included data from 79 patients with various types of peripheral neuropathies—both autoimmune and hereditary—and 50 healthy volunteers as a control group. Using a system of inertial sensors placed on different parts of the body and plantar pressure insoles, researchers collected multiple biomechanical parameters during a two-minute walking test. This system allowed for detailed analysis of spatiotemporal variables (such as walking speed, step length, or cadence), joint angles, and pressure distribution on the soles of the feet.

The results indicate that this system can detect prototypical abnormal gait patterns associated with peripheral neuropathies, such as ataxia—an uncoordinated or unstable gait—and steppage gait—an exaggerated knee lift to prevent the foot from dragging. These patterns are common in many neuropathies, and the digital system made it possible to identify them with great precision.

In addition, many of the biomechanical parameters measured correlate with conventional clinical scales, such as the MRC (Medical Research Council) score and the i-RODS scale, which are commonly used to assess strength and disability in this patient population.

A Useful Tool for Follow-Up and Clinical Trials

One of the study’s key contributions is its longitudinal component. In a subgroup of patients who experienced clinically relevant changes over time, the system detected significant modifications in several biomechanical parameters, especially those related to knee, ankle, hip function, and plantar pressure. This demonstrates the system’s potential as a continuous monitoring tool and an objective functional biomarker for tracking the progression of peripheral neuropathies.

This study is particularly relevant in the current context, where the availability of new treatments for some peripheral neuropathies makes it more important than ever to have sensitive and objective tools to evaluate their effectiveness. Although conventional clinical scales are useful, they often have limited sensitivity and may fail to detect subtle but clinically meaningful changes. The use of biomechanical sensors helps overcome these limitations and paves the way for more accurate and personalized evaluation, both in clinical practice and in future therapeutic trials.

According to Dr. Pascual-Goñi, “The study shows that wearable technology based on inertial sensors and pressure insoles can provide an accurate and less subjective evaluation of gait, with applications in both clinical and research settings. It could facilitate early detection of changes, personalized patient monitoring, and the assessment of treatment efficacy in clinical trials.”

Reference article:

Tejada-Illa C, Pegueroles J, Claramunt-Molet M, Pi-Cervera A, Heras-Delgado A, Gascón-Fontal J, Idelsohn-Zielonka S, Rico M, Vidal N, Martín-Aguilar L, Caballero-Ávila M, Lleixà C, Collet-Vidiella R, Llansó L, Carbayo Á, Vesperinas A, Querol L, Pascual-Goñi E. Digital biomechanical assessment of gait in patients with peripheral neuropathies. J Neuroeng Rehabil 2025;22:159. https://doi.org/10.1186/s12984-025-01694-w

On Tuesday, July 29, the Sant Pau Research Institute (IR Sant Pau) welcomed Dr. Vladyslav Vyazovskiy, professor at the University of Oxford and one of the world’s most recognized voices in sleep research. Dr. Vyazovskiy chaired the dissertation committee for Diego del Castillo Berges, a predoctoral researcher in the Molecular Synapse Physiology group led by Dr. Àlex Bayés.

The dissertation, titled Alterations in NREM Sleep Accompany Dysregulation of Synaptic Proteome Dynamics in Syngap1 Heterozygous Mice, focuses on non-rapid eye movement (NREM) sleep, one of the two major phases of sleep characterized by slow and synchronized brain activity. This is essential for energy restoration and memory consolidation. The study specifically explores how deep sleep affects the molecular functioning of synapses in a mouse model carrying a mutation in the SYNGAP1 gene, one of the most common monogenic causes of intellectual disability and neurodevelopmental disorders.

Using proteomic and electroencephalographic analysis techniques, the study indicates that these mice exhibit significant alterations both in the molecular mechanisms regulating neuronal connections and in their sleep patterns. Under normal conditions, about 10% of the synaptic proteome follows rhythmic oscillations throughout the day. In the mutant mice, about half of these oscillations are lost, but a new set of cyclic proteins emerges, suggesting not just a loss of rhythmicity, but a pathological reorganization of synaptic function.

On a functional level, SYNGAP1 heterozygous mutant mice maintain a generally normal sleep architecture and circadian regulation of the sleep-wake cycle, but they show subtle changes in NREM sleep microarchitecture. They experience fewer microarousals and more stable periods of deep sleep, but with altered brain activity: there is an increase in delta power (associated with slow waves) and a decrease in sigma power, which reflects the activity of sleep spindles—brief, rapid oscillations typical of NREM sleep involved in memory consolidation and sensory disconnection during rest. While the mechanisms regulating brain activity during deep sleep and across the day are preserved, the pattern of sleep spindles is altered and no longer follows the usual slow rhythm. This change, together with the reduction in microarousals, suggests a possible dysfunction in the noradrenaline signaling system.

The dissertation proposes that this dysregulation of proteomic dynamics and brain oscillations during NREM sleep could be related to the cognitive and behavioral deficits observed in SYNGAP1-related disorders. Furthermore, it suggests that therapeutic strategies aimed at restoring the characteristic oscillations of NREM sleep may have beneficial effects.

Dr. Vyazovskiy’s presence as chair of the dissertation committee brought both scientific and symbolic value to the defense. His group, based in the Department of Physiology, Anatomy, and Genetics at the University of Oxford, investigates the synaptic, cellular, and neurophysiological mechanisms that regulate the sleep-wake cycle. It also studies how these processes are altered in neurological and psychiatric disorders, aging, and metabolism. He is particularly well known for his contributions to the synaptic homeostasis hypothesis, which posits that sleep plays a vital role in restoring the balance of brain plasticity accumulated during wakefulness.

His research also explores innovative areas such as local sleep (in which different brain regions may be in different functional states), torpor and hibernation, the effects of psychedelic compounds such as 5-MeO-DMT, and the detailed analysis of circadian rhythms and brain oscillations across multiple timescales.

His visit to Sant Pau was a valuable opportunity to promote scientific exchange and strengthen ties with leading neuroscience groups on the international stage. It also represents recognition of the achievements of the Molecular Synapse Physiology group, a pioneer in the study of the human synaptic proteome and the molecular alterations involved in neurological and developmental disorders.

Vitamin D supplementation may have effects that go far beyond bone metabolism. In patients with decompensated cirrhosis, correcting vitamin D deficiency is associated with improvements in frailty, muscle strength, inflammation, and cognitive function—especially working memory. These findings are supported by two articles recently published in the scientific journals Medical Sciences and Nutrients as part of a multidisciplinary, international collaboration coordinated by Hospital Gregorio Marañón in Madrid and Hospital de Sant Pau in Barcelona.

The studies were led by the Departments of Digestive Diseases at Hospital Gregorio Marañón and Hospital de Sant Pau–Sant Pau Research Institute (IR Sant Pau), along with the Sant Pau University School of Nursing. They were conducted in collaboration with research groups from CIBERehd and CIBERSAM and the University of Melbourne (Australia). The work was supported by the European Commission and the Carlos III Health Institute.

Frailty and Muscle Strength

The first study, published in Medical Sciences, showed that vitamin D supplementation, as part of a multifactorial nutritional intervention, significantly improves frailty and muscle strength and mass in patients with decompensated cirrhosis and vitamin D deficiency.

The study included 39 patients who had recently been hospitalized for complications related to liver cirrhosis. Once low vitamin D levels were confirmed, treatment with supplements was initiated in accordance with current clinical guidelines, along with other micronutrients as needed. Over a 12-month period, researchers assessed the impact of this intervention on frailty (Fried index), handgrip strength, body composition, and quality of life.

“Our research group has been studying frailty in cirrhosis for years. We knew that vitamin D deficiency is very common in patients with advanced cirrhosis, but until now, there was no solid evidence on whether treating it had a real clinical impact on frailty.” This is explained by Dr. Germán Soriano, researcher in the Digestive Diseases group at IR Sant Pau and clinical lead at Hospital de Sant Pau. He is one of the corresponding authors of the study.

After six months, patients showed a significant improvement in the Fried frailty index and a sustained increase in muscle strength throughout the year-long follow-up. At 12 months, there was also an increase in lean and fat mass. “Most importantly, not only did biochemical and nutritional parameters improve, but so did clinical and functional variables such as grip strength, anxiety levels, and quality of life,” notes Dr. Soriano. “This has important implications for the well-being and independence of these patients.”

The observational study highlights a low-cost, easily implemented strategy to improve the functional status of individuals with advanced liver disease—a particularly vulnerable population. “Improving frailty may reduce the risk of further hospitalizations, falls, and mortality. Incorporating vitamin D deficiency screening and treatment into routine clinical management of these patients could make a meaningful difference,” Dr. Soriano concludes.

Improvements in Inflammation and Cognitive Function

The second study, published in Nutrients, showed that vitamin D supplementation can improve cognitive function and reduce inflammation in patients with decompensated cirrhosis. This is one of the most severe forms of chronic liver disease and is characterized by chronic inflammation, impaired immune response, and often, cognitive dysfunction. In this context, the researchers hypothesized that vitamin D deficiency—very common in these patients—could be contributing to these impairments.

“Our data suggest that vitamin D plays a key role in regulating inflammation and cognitive performance in patients with advanced cirrhosis,” says Dr. Rita García-Martínez of Hospital Gregorio Marañón, who led the project at that site.

The study included 39 patients with decompensated cirrhosis and vitamin D deficiency. Twenty-seven completed six months of follow-up, and 22 were evaluated at the 12-month mark. All patients received a daily oral vitamin D supplement aimed at restoring adequate blood levels of the vitamin.

Results indicated that patients with lower vitamin D levels had poorer cognitive function, particularly in tasks involving working memory and learning. Similarly, patients with higher levels of inflammatory markers such as the cytokine IL-1β also performed worse on tasks requiring processing speed and attention. After supplementation, not only was there a significant improvement in cognitive performance, but levels of certain proinflammatory cytokines, including IL-1β and IL-6, were also reduced. “These findings strengthen the link between systemic inflammation and cognitive impairment in cirrhosis, opening the door to possible therapeutic interventions,” notes Dr. Rafael Bañares, a physician in the Digestive Diseases Department at Hospital Gregorio Marañón. Along the same lines, Dr. García-Martínez points out that vitamin D “could become a safe, affordable, and easy-to-administer therapeutic tool to prevent common complications in patients with advanced liver disease.”

A Simple Intervention With Great Potential

The results of these two studies underscore the need not to underestimate vitamin deficiencies in patients with cirrhosis, especially in the decompensated stages of the disease. Vitamin D supplementation appears to be a low-cost, accessible, and safe strategy with potential impact on quality of life, functional autonomy, and clinical prognosis in these patients.

The researchers also included a gender-based analysis, identifying some differences in clinical response to supplementation. “It’s essential to consider sex and gender in clinical care. In this case, both women and men showed clear improvements in muscle strength, indicating that supplementation is beneficial across genders,” emphasizes Dr. Soriano.

The researchers advocate for the systematic screening and treatment of vitamin D deficiency in the follow-up protocols for patients with decompensated cirrhosis as a complementary tool to improve their functionality, well-being, and clinical outcomes. “Our results support incorporating this practice routinely as an additional and effective resource in the comprehensive care of these patients,” concludes Dr. García-Martínez.

Reference articles:

1. Díaz-Ruíz R, Poca M, Román E, Cuyàs B, Bañares I, Morales Á, Hernández Martínez-Esparza E, Panadero R, Velasco C, Rapado-Castro M, Bretón I, Bañares R, Soriano G, García-Martínez R. Treatment of vitamin D deficiency in decompensated patients with cirrhosis is associated with improvement in frailty. Med Sci (Basel) 2025;13. https://doi.org/10.3390/medsci13010030
2. Diaz-Ruiz R, Poca M, Roman E, Panadero-Gomez R, Cuyàs B, Bañares I, Morales A, Puerto M, Lopez-Esteban R, Blazquez E, Fernández-Castillo M, Correa-Rocha R, Rapado-Castro M, Breton I, Bañares R, Soriano G, Garcia-Martinez R. Vitamin D supplementation is associated with inflammation amelioration and cognitive improvement in decompensated patients with cirrhosis. Nutrients 2025;17:226. https://doi.org/10.3390/nu17020226

A new study has identified a promising therapeutic pathway to restore the ability of HDL lipoproteins to remove cholesterol from vascular smooth muscle cells (VSMCs), which are involved in the development of atherosclerosis. The research was led by scientists from the CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), the Sant Pau Research Institute (IR Sant Pau), and the Clinical Biochemistry Department of Sant Pau Hospital in Barcelona.

Vascular smooth muscle cells can transform into foam cells during the atherosclerotic process, making up as much as 70% of this cell type within the arterial plaque. These cells lose their ability to efficiently remove cholesterol, which contributes to the progression of cardiovascular disease.

The study, published in the journal Biomedicine & Pharmacotherapy and led by Joan Carles Escolà-Gil, Francisco Blanco-Vaca, and Marina Canyelles, demonstrates that pharmacological activation of the Liver X Receptor (LXR) allows the lost ability of VSMCs to release cholesterol to be restored. This promotes its transport to fecal excretion.

An Innovative Therapeutic Combination

The researchers used an experimental drug that activates the LXR receptor. When administered to cholesterol-loaded VSMCs, it significantly increased the transport of cholesterol to HDL in the blood, the liver, and finally to the feces.

Acyl-CoA cholesterol acyltransferase (known as ACAT) is an enzyme that converts free cholesterol into esterified cholesterol for storage within the cells. Under normal conditions, this prevents excessive accumulation of free cholesterol. However, in foam cells, this action contributes to the retention of cholesterol within the cell. Inhibiting this enzyme prevents cholesterol from being stored, facilitating its elimination from the body. In this study, the drug that activates LXR was combined with another drug that inhibits the ACAT enzyme, which further enhanced this process.

“The results indicate that the transition of VSMCs into foam cells significantly impairs their ability to expel cholesterol. However, this function can be restored by activating the LXR receptor, which opens new opportunities to reduce cholesterol buildup in the arterial wall,” highlights Dr. Carla Borràs, first author of the study and researcher at IR Sant Pau and CIBERDEM.

For his part, Dr. Joan Carles Escolà, one of the study’s directors, points out that “the combination of drugs that activate the LXR receptor with ACAT inhibitors could represent a new synergistic therapeutic strategy to slow the progression of atherosclerosis, although it will be necessary to develop delivery vehicles that can specifically target these treatments to foam cells.”

Researchers from the CIBER of Cardiovascular Diseases (CIBERCV), the Institute of Biomedical Research of Barcelona, and the CSIC also participated in the study.

Article Reference:

Carla Borràs, Noemí Rotllan, Raquel Griñán, David Santos, Arnau Solé, Chen Dong, Qi Zhao, Vicenta Llorente-Cortes, Marta Mourín, Begoña Soto, Mercedes Camacho, Mireia Tondo, Marina Canyelles, Francisco Blanco-Vaca, Joan Carles Escolà-Gil. Restoring cholesterol efflux in vascular smooth muscle cells transitioning into foam cells through Liver X receptor activation. Biomedicine & Pharmacotherapy, 2025, Volume 188, 118178, https://doi.org/10.1016/j.biopha.2025.118178