Experts agree that today we are much closer to defeating Alzheimer’s and that we are living through a historic paradigm shift. There is still no cure, but for the first time it has been possible to slow the course of the disease thanks to a turning point: a new generation of drugs that remove the beta-amyloid protein that accumulates in patients’ brains and slow the progression of Alzheimer’s by 30%. Plasma biomarkers are also highlighted as a revolution in diagnosis at all stages of the disease through a simple blood test. They also deliver a public health message to society: 45% of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors. These are some key conclusions from the recent meeting marking the 20th anniversary of the Memory Unit (MU) at Hospital de Sant Pau, which brought together world experts, patients, and families.

“We have very robust biomarkers that enable highly accurate diagnosis, drugs that modify disease progression, and 130 additional medications currently under study that broaden the range of strategies, including approaches focused on inflammation and synaptic protection… Every day we can and must open another door in the fight against Alzheimer’s, and I am convinced that we will ultimately defeat this neurodegenerative disease,” emphasized the renowned neurologist Teresa Gómez-Isla, Chief of the Memory Disorders Division at Mass General Brigham (Massachusetts General Hospital) and Professor of Neurology at Harvard Medical School (U.S.), who was also part of Sant Pau’s MU in its early years.

“In 2026, the 21st century begins in Alzheimer’s,” stated Dr. Juan Fortea, current director of the MU. “These new drugs represent a radical change and are only the first step toward a future we have every reason to view with great optimism.” Dr. Alberto Lleó, Director of the Neurology Department at Sant Pau, noted that “we will see many treatments coexisting.” He added that these changes “pose a major challenge: a new model of patient management requiring much closer monitoring. New infrastructure, personnel, and technology are needed.” He also stressed that Sant Pau “is very well positioned to continue being a global leader in this field.”

Dr. Adrià Comella, Director of Hospital de Sant Pau, stated at the opening of the event that “our center is a leader and pioneer in this field, always working from a systems perspective and through contributions and collaborations with other institutions. The Memory Unit is a clear example.” Meanwhile, Dr. Jordi Surrallés, Director of IR Sant Pau, highlighted “our global leadership in Alzheimer’s research and in the genetic forms of this disease, and we are carrying out intensive work in the identification of biomarkers.”

A Decisive Advance: Plasma Biomarkers

Dr. Gómez-Isla, with an extensive clinical, research, and teaching career—who treated former Barcelona mayor Pasqual Maragall—studies brain changes associated with aging, particularly in the earliest stages of Alzheimer’s, mechanisms of brain resilience, and the validation of new imaging biomarkers for early detection and intervention. She addressed these topics in “Alzheimer’s: Deciding the Future of Memory” and stated that “with the MU came a conviction: science must go hand in hand with patient care,” recalling the beginnings of a career defined by translational research.

“Imaging and plasma biomarkers have been a key breakthrough. Previously, definitive diagnosis was only possible through postmortem brain analysis. Now we have tools that allow us to identify the disease during life, such as the plasma biomarker p-tau217, which has demonstrated a strong ability to distinguish Alzheimer’s from other neurodegenerative diseases, even outperforming other blood and MRI biomarkers. These simple, noninvasive methods open the door to reliable and more accessible detection.”

Another advance is the recently approved drugs. At Massachusetts General Hospital, data from the first two years of treatment have been analyzed: “We need to see how the benefits observed in clinical trials translate into patients’ daily lives, but these advances are a ray of hope for patients and families.” She added that “measuring benefits in each patient is not easy, because each individual is different and comorbidities make it difficult to understand how Alzheimer’s progresses and to assess the effectiveness of these treatments.”

She also reviewed important milestones in Alzheimer’s research, such as genetic evidence. “It was known that 90% of Alzheimer’s cases occurred in people over sixty years of age, while 10% affected younger patients, often due to genetic causes. This evidence was crucial in formulating the amyloid cascade hypothesis: first, beta-amyloid accumulates abnormally, then the tau protein, and finally progressive loss of neurons and synapses occurs, leading to clinical symptoms.”

She also highlighted a pioneering 1996 study demonstrating marked neuronal loss in the entorrinal cortex—key for memory and recollection—from very early disease stages, disproving the belief that aging inevitably entailed generalized neuronal loss. “A healthy human brain has about 7 million neurons in this region. In patients with very mild Alzheimer’s symptoms, a 30% neuronal death rate was observed, which could reach 70% in advanced stages. This indicated that brain damage began many years before the first symptoms and underscored the need for earlier and better diagnosis.” Today we know that brain amyloid can begin to be detected up to fifteen years before symptom onset in certain cases, defining a long silent phase that represents the best therapeutic window before neuronal loss becomes irreversible.

Sant Pau and the Memory Unit, A Global Reference in Alzheimer’s

Hospital de Sant Pau created Spain’s first Neurology Department in 1882. Since then, it has remained a pioneer in this field in both clinical care and research. In 2005, it created the MU with four members: Dr. Rafael Blesa, Dr. Alberto Lleó, Dr. Isabel Sala, and Dr. Gómez-Isla; today, it is an interdisciplinary team of 75 professionals. “Additionally, Dr. Isabel Illa was instrumental in promoting research and establishing the laboratory during the early years,” said Dr. Lleó.

Today, Sant Pau holds a key position on the global Alzheimer’s landscape, and the MU has recently been designated a CSUR (National Reference Center) for rare diseases in adults presenting with cognitive disorders. It is the world’s leading recruiting center for clinical trials in this disease, notably through the SPIN Cohort (Sant Pau Initiative on Neurodegeneration), which is essential for biomarker discovery and validation, and the DABNI Project (Down Alzheimer Barcelona Neuroimaging Initiative), an intensive biomarker study in adults with Down syndrome (DS) and Alzheimer’s. “We have conducted more than 1,000 clinical visits with DS patients with Alzheimer’s, making it by far the largest biomarker cohort in DS worldwide,” explained Dr. Fortea. “We have reconceptualized DS, and in 2024 it was incorporated into U.S. diagnostic criteria.”

All of this has made the center a benchmark for collaboration. Clear examples include the HUB Alzheimer Barcelona, bringing together six reference centers in Barcelona; the Global Brain Health Institute (GBHI), coordinated by the University of California (U.S.) and Trinity College Dublin to promote a global network of brain health leaders; and Brave-AD (Barcelona REsearch on APOE, Vascular Risk and Eye in Alzheimer’s Disease), among others.

Currently, the MU is conducting 28 clinical trials involving the main molecules related to Alzheimer’s and is a reference center in biomarkers. Notably, it has identified a new genetic form of Alzheimer’s: specifically, having two copies of the APOE4 gene causes the disease in 95% of cases—previously considered only a risk factor, it is now known that virtually all individuals with this duplication will develop the disease. Between 2% and 3% of the population and 1 in 5 people with dementia carry this duplicated gene. “Being able to predict who will develop the disease can be extremely useful to begin treatment before the first symptoms appear,” stated Dr. Fortea regarding the study published in Nature Medicine.

Another study published in JAMA Neurology reinforces the role of blood testing in the future of dementia diagnosis and monitoring, demonstrating that the plasma biomarker p-tau217 achieves 90–95% accuracy, comparable to cerebrospinal fluid biomarkers, even in the earliest stages of the disease when symptoms are not yet evident.

Keynote Lecture by Dr. Rafael Blesa, Founder of the MU

Under the title “Four Decades of Research in Alzheimer’s Disease and the Development of Memory Units in Catalonia”, Dr. Rafael Blesa, an internationally recognized neurologist in Alzheimer’s research and study, founder of the Sant Pau MU and former Director of the Neurology Department at Sant Pau, reviewed the most important milestones in recent Alzheimer’s history, including studies on the genetics of the disease, the amyloid cascade hypothesis, approval of the first drugs to treat symptoms, the creation of family associations, pioneering programs such as PICOGEN, diagnostic protocols, advances in neuroimaging and biomarkers, and the establishment of memory units in Catalan hospitals.

Looking ahead, he stated that “there will be more than symptomatic treatment with the newly approved drugs” and that “we must continue investigating the cause of the disease, because none of the current therapies can cure it.” He also emphasized “interdisciplinary care aligned with social policies, frameworks such as PLADEMCAT that guide comprehensive care, and public education about modifiable risk factors in the development of Alzheimer’s.”

An international study led by researchers from the Institut de Recerca Sant Pau (IR Sant Pau) shows that advanced use of magnetic resonance imaging (MRI) allows much more accurate identification of patients with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). These are two rare and clearly underdiagnosed atypical parkinsonian disorders.

The study, published in The Journal of Prevention of Alzheimer’s Disease, shows that this strategy improves early diagnosis and transforms the design of clinical trials, making them more precise and feasible for diseases for which no disease-modifying treatment currently exists.

“These are diseases that cause balance problems, falls, stiffness, or difficulties with speech and movement. Many patients initially present as if they had Parkinson’s disease or are simply older adults with mobility difficulties,” explains Dr. Jesús García-Castro, researcher in the Neurobiology of Dementias Group at IR Sant Pau and neurologist at Hospital de Sant Pau. He is the first author of the study. “This means they are greatly underdiagnosed, and for years we have not known with enough certainty which disease each patient actually had.”

What PSP and CBD Are and Why They Are Confused With Parkinson’s Disease

PSP and CBD belong to a group of neurodegenerative diseases known as tauopathies, which are characterized by the abnormal accumulation in the brain of tau protein, a protein essential for normal neuronal function.

When tau is deposited pathologically, it causes progressive damage to different brain regions. In PSP and CBD, this damage particularly affects areas involved in movement control, balance, posture, speech, and certain cognitive functions, which explains why their initial symptoms closely resemble those of Parkinson’s disease.

Unlike Alzheimer’s disease—another well-known tauopathy—PSP and CBD belong to the subgroup of four-repeat tauopathies, with their own distinct biological characteristics. However, for years these differences could not be clearly identified during life, leading to imprecise diagnoses and significant clinical confusion.

“These diseases are, in a way, halfway between Alzheimer’s and Parkinson’s,” notes Dr. Ignacio Illán-Gala, researcher in the Neurobiology of Dementias Group at IR Sant Pau and neurologist at Hospital de Sant Pau, and senior author of the study. “They resemble Parkinson’s because of their motor symptoms, but they share with Alzheimer’s the fact that they are caused by tau pathology. The problem is that, until now, we did not have reliable tools to distinguish them properly.”

Imprecise Diagnoses and Clinical Trials That Fail

For years, the lack of objective diagnostic tools has been one of the main obstacles to treatment development in these tauopathies. Patient selection for clinical trials has relied almost exclusively on clinical criteria, especially in early stages, when symptoms are still nonspecific and overlap across different diseases.

The same clinical syndrome can correspond to different underlying pathologies, and the same disease can manifest in very different ways. This heterogeneity has led many clinical trials to include biologically mixed populations, drastically reducing their ability to detect true therapeutic benefits.

This issue is particularly relevant in CBD, where a significant proportion of patients actually have Alzheimer’s disease. Without adequate biological filtering, the cohorts used in clinical trials are biologically contaminated, critically limiting their usefulness.

How Magnetic Resonance Imaging Makes It Possible to Differentiate PSP and CBD

The study indicates that structural magnetic resonance imaging can address a long-standing gap in these tauopathies: the absence of reliable in vivo biomarkers capable of identifying the true underlying pathology when symptoms are still nonspecific.

By analyzing patterns of brain atrophy in detail, the researchers developed models capable of estimating with high probability whether a patient has PSP or CBD, even at very early stages of the disease. “MRI has two fundamental functions,” explains Dr. García-Castro. “On the one hand, it helps us diagnose much more reliably at early stages. On the other hand, it allows us to measure disease progression objectively.”

The key to the study lies in identifying disease-specific MRI signatures based on the combination of structural changes across different brain regions. In PSP, the signature is characterized mainly by involvement of deep brain structures, particularly the brainstem, together with more selective changes in certain cortical areas. In CBD, the pattern is different and shows more marked involvement of cortical regions, especially those related to motor control and sensory integration.

“Although they may look very similar clinically, at the brain level PSP and CBD damage the brain in different ways,” says Dr. Illán-Gala. “These differences are reflected on MRI, and by combining them into a signature, we can much better determine which disease each patient has.”

Smaller, Feasible Clinical Trials With Real Impact for Patients

Beyond improving diagnostic accuracy, the study proves that MRI can also be used as a longitudinal follow-up tool in clinical trials targeting these tauopathies. By using disease-specific MRI signatures as objective measures of disease progression, the researchers demonstrate that it is possible to detect structural brain changes with much greater sensitivity than with traditional clinical scales.

In classic trial designs based on clinical variables—such as functional or symptom severity scales—demonstrating that a treatment modifies disease progression usually requires long follow-up periods and considerable sample sizes, often reaching several hundred patients. This approach is especially problematic in rare diseases such as PSP and CBD, where recruitment is slow, costly, and difficult to sustain over time.

Analyses performed in the study show that using MRI as an outcome measure substantially changes this scenario. In PSP, applying disease-specific MRI signatures could reduce the number of participants required by approximately 50% in a 12-month clinical trial compared with designs based solely on clinical scales. In CBD, where clinical and diagnostic heterogeneity is even greater, the impact is even more pronounced: use of these objective measures could lead to an approximately 80–85% reduction in the required sample size to detect a therapeutic effect with the same statistical power.

“For a company or an academic consortium to commit to a clinical trial, it has to be feasible,” adds Dr. Illán-Gala. “If a trial requires a thousand patients, it is practically impossible. But if it can be conducted with a reasonable number of well-selected individuals and objective measures of progression, then there is a real chance of demonstrating whether a treatment works.”

In this context, the researchers emphasize that these are not merely rare diseases but conditions that are both infrequent and clearly underdiagnosed. Methodological limitations have so far been a key barrier to therapeutic development and to the availability of real options for patients.

Research Continuity and New PERIS-Funded Lines of Work

This line of research has direct continuity in projects currently underway at IR Sant Pau. In the 2025 call of the PERIS program of the Department of Health of the Government of Catalonia, the center received funding to advance the early diagnosis of four-repeat tauopathies, including PSP and CBD. This is done through the combination of plasma biomarkers and advanced imaging techniques.

This project, led by Dr. Illán-Gala, builds directly on the results now published and aims to shift diagnosis toward minimally symptomatic stages, when future disease-modifying treatments are more likely to be effective.

“Our goal is to reach a situation similar to that of Alzheimer’s disease, where a combination of a blood test and an MRI scan allows these diseases to be diagnosed at very early stages and with much greater confidence,” explains Dr. García-Castro.

“These conditions are far more common than we think, but we do not know how to detect them properly,” concludes Dr. García-Castro. “Improving diagnosis is the first step so that these patients, who currently have no therapeutic options, can begin to have them.”

Reference Article:

García-Castro J, VandeVrede L, Donohue MC, Vaqué-Alcázar L, Rubio-Guerra S, Selma-González J, Heuer HW, Morcillo-Nieto AO, Franquesa M, Dols-Icardo O, Bejanin A, Belbin O, Fortea J, Alcolea D, Carmona-Iragui M, Abdelnour C, Barroeta I, Santos-Santos M, Sánchez Saudinós MB, Sala I, Lleó A, Gorno-Tempini ML, Mandelli ML, Raman R, Wills A-MA, Barragan E, Litvan I, Boeve B, Dickerson B, Grossman M, Huey ED, Irwin DJ, Pantelyat A, Tartaglia C, Rojas JC, Boxer AL, Illán-Gala I, Four Repeat Tau Neuroimaging Initiative (4RTNI) and the AL108-231 Investigators. Potential role of MRI to optimize clinical trial design for progressive supranuclear palsy and corticobasal degeneration. J Prev Alzheimers Dis 2026;13:100486. https://doi.org/10.1016/j.tjpad.2026.100486

The second edition of the Women and Girls in Science Celebration, organized this Sunday by the Sant Pau Research Institute (IR Sant Pau), once again transformed the Panoramic Area of Tibidabo Amusement Park into a meeting space between science and the public. More than 4,000 people attended throughout the day to accompany Mariona, an eight-year-old girl passionate about science, in this celebration held in the framework of the International Day of Women and Girls in Science.

During the event, families enjoyed more than twenty educational and participatory workshops and activities led by professionals from IR Sant Pau, helping to raise awareness and promote a more inclusive future in science. The project also highlights the role of women in science, showcasing real examples of female researchers who share their professional and personal experiences with the goal of promoting gender equality in this field.

At IR Sant Pau, the commitment to gender equality is also reflected in the structure of its research staff. Women represent 65% of research personnel in the R2 and R3 categories, 67% of early-stage researchers, and 44% of those leading research groups. Likewise, female representation is the majority in management teams and in scientific-technical platforms, at 80% and 83%, respectively. These figures demonstrate strong female participation at all stages of the scientific career.

Dr. Jordi Surrallés, director of IR Sant Pau, highly valued the celebration of this second edition. “We want girls and boys to see that science is accessible, exciting, and also a space for them. Creating female role models from an early age is key to building more diverse and more excellent research,” he stated.

The Minister of Health of the Government of Catalonia, Olga Pané, underscored the importance of initiatives like this to advance toward a more inclusive and equitable science. “It is essential to maintain the scientific spirit and encourage our girls to continue in the field of science. We have made significant progress, but we have not yet reached where we want to be. We need more women researchers, more women leading teams, and more women in decision-making positions. The science of the future must include everyone’s talent, because only then will it be better and fairer.”

The minister also noted that female representation in research has grown significantly lately, although inequalities persist at leadership levels. “Today, women account for more than 50% of doctoral students, and three-quarters of healthcare professionals are women. However, this same representation is not yet fully reflected in executive leadership positions. That is why it is essential to continue promoting role models, breaking stereotypes, and defending science against any form of denialism.”

Finally, she issued a collective call to protect and elevate scientific research as a driver of social progress. “Science is a tool for protection and progress. We must defend and value it, especially in the face of narratives that question it. Events like this not only inspire vocations but also help build a more equal and stronger future for our country.”

A Day Filled With Activities

The event offered a wide variety of proposals designed to bring science and research closer to audiences of all ages. Among the most notable activities were workshops such as The Superpower of Blood and Discovering the Basis of Life — DNA, where participants were able to explore fundamental concepts of biomedicine practically.

Sessions such as Experience Science by Conducting Experiments! were also held, along with workshops on the influence of sex and gender on medication response and spaces dedicated to understanding how the respiratory, digestive, and cardiovascular systems function. The activity I Want to Have a Super Heart! focused on the importance of healthy habits from childhood.

Hands-on learning also played a central role with a cardiopulmonary resuscitation (CPR) workshop, which allowed children and adults to become familiar with basic life-saving maneuvers. For younger audiences, activities such as My Body Is Awesome! and the session How Are Babies Born? addressed different aspects of development and health from a scientific and educational perspective.

The day also featured the space The Human Body: A 3D Journey, with three-dimensional models that allowed visitors to explore organs and systems visually and interactively, in addition to scientific animations and recreational activities for younger children.

Children who had completed the Mariona project missions throughout the year were able to exchange their wristbands for a personalized calculator featuring Mariona’s image, a gift from Casio, reinforcing the experiential and ongoing nature of the initiative. In the words of Dr. Jordi Surrallés, “Initiatives like this are part of our responsibility as a research institute: to open our doors, share knowledge, and actively contribute to a more informed and equitable society.”

The Mariona Project

The “Mariona Researcher” project is an educational and outreach initiative developed by IR Sant Pau. Mariona is a character who symbolizes an eight-year-old girl passionate about science and medicine, with the purpose of inspiring girls, boys, and young people to explore the world of scientific research. Around this age—eight years old—is when girls often begin to lose interest in science, due both to persistent stereotypes and to the lack of role models, a situation this project seeks to address.

Science With a Gender Perspective

IR Sant Pau continuously promotes dialogue with society, aligned with its RRI plan and its objectives in scientific education and citizen participation. As a CERCA center and as a Unit of Scientific Culture and Innovation accredited by FECYT, its commitment to bringing research closer to society is firm. As the only Catalan research institute with a cross-cutting research program in gender, IR Sant Pau serves as a spokesperson for the latest scientific advances and highlights the importance of research with a gender perspective. It also highlights women’s role in research and the future of science.

For its part, Tibidabo Amusement Park, known for its dedication to educational and charitable projects, collaborates with various organizations to give visibility to missions with significant social impact. In this context, the park is an ideal venue to showcase IR Sant Pau’s work to families.

Several companies also participated in this Women and Girls in Science Celebration. The second edition of the event was supported by Casio, GAES Junior, Grupo Julià, Miniland, and Tais Events. DiR, Dansa Menchu Durán, the Guinardó Municipal Sports Center, and MODIband also took part, contributing to the development of various activities throughout the day.

A study led by the EAP Dreta de l’Eixample and EAP Sardenya Primary Care teams, together with the Institut de Recerca Sant Pau (IR Sant Pau), shows that patients with chronic obstructive pulmonary disease (COPD) experience more frequent and more severe respiratory exacerbations during periods with high levels of environmental pollution. The work was carried out by Dr. Marta García, Dr. Daniel Planchuelo, Dr. Lluís Cuixart, and Dr. Carles Brotons, all members of the Primary Care research group.

Published in Revista Clínica de Medicina de Familia, the study compares a year with high pollution levels (2017) with a year of better air quality (2021), a period marked by restrictions associated with the COVID-19 pandemic, which led to a significant reduction in traffic and urban activity. The findings reinforce the importance of public policies aimed at reducing atmospheric pollutants.

Air pollution is a major public health issue and has a particularly strong impact on people with chronic respiratory diseases. As highlighted by Dr. Lluís Cuixart, “People with COPD are especially vulnerable to environmental pollution, because any deterioration in air quality can act as a trigger for exacerbations with a relevant clinical impact.”

In cities such as Barcelona, exposure to pollutants like nitrogen dioxide and fine particulate matter has been consistently associated with a higher risk of COPD exacerbations, a phenomenon that this study analyzes from a clinical and healthcare perspective.

More Exacerbations and Greater Severity in Years With Poorer Air Quality

The study included 150 patients with COPD treated at a primary care center in Barcelona, distributed into two equivalent cohorts. In 2017, a year with high pollution levels, 41.3% of patients experienced at least one respiratory exacerbation, compared with 25.3% in 2021, when air quality improved markedly.

In addition to being more frequent, exacerbations were also more severe in the year with higher environmental pollution. In 2017, more emergency department visits and hospital admissions were recorded, whereas in 2021 most exacerbations could be managed in the outpatient setting.

According to Dr. Marta García, principal investigator of the study, “The results show that not only do exacerbations increase when air quality is worse, but they also tend to be more severe and to require more complex healthcare, with the resulting impact on both patients and the healthcare system.”

The Role of Comorbidities and the Pandemic Context

The analysis considered several clinical and demographic variables, including age, smoking status, lung function, and cardiovascular comorbidities. In this regard, Dr. Cuixart emphasizes that “in patients with COPD, it is essential to interpret the effects of pollution in the context of associated diseases, since common conditions such as arterial hypertension can modulate both the frequency and the severity of exacerbations.”

Regarding cardiovascular events, the study did not find significant differences in incidence between the two years. However, a trend toward less severe episodes in 2021 was observed, with a higher proportion of patients managed on an outpatient basis. The authors stress that these findings should be interpreted with caution, as the sample size does not allow firm conclusions to be drawn for this outcome.

The context of the COVID-19 pandemic in 2021 is another factor to consider. Mobility restrictions, widespread mask use, and the reduction in non-COVID respiratory infections may have contributed, at least in part, to the lower incidence of exacerbations observed that year.

Implications for Public Health and Clinical Practice

Despite its limitations, the study provides local evidence that reinforces the role of environmental pollution as a modifiable risk factor in COPD. “Improving air quality is not only an environmental issue but also a health intervention with a direct impact on particularly vulnerable patients,” notes Dr. Cuixart. “Our data support the need to integrate pollution monitoring into the prevention and management of COPD, together with the control of comorbidities.”

The researchers highlight the need for future prospective and multicenter studies to further explore the causal relationship between exposure to pollutants and respiratory and cardiovascular clinical outcomes. Meanwhile, the results support emission reduction strategies and urban policies aimed at improving air quality as a key measure to reduce the disease burden in patients with COPD.

Reference Article:

García Torres M, Planchuelo Calatayud D, Cuixart Costa L, Brotons Cuixart C. Impact of Environmental Pollution on Respiratory Exacerbations and Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease. A Retrospective Cohort Study. Rev Clin Med Fam. 2025;18(4):324–330. doi:10.55783/rcmf.180404.

Acute myeloid leukemia (AML) is the most common acute hematologic malignancy in adults and one of those with the poorest prognosis. Unlike other hematologic diseases, therapeutic advances in AML have historically been modest, and overall survival remains limited, largely due to the persistence of treatment-resistant cellular subpopulations. Understanding the biological mechanisms that explain why some patients respond better than others to the same therapy is one of the main current challenges in this field.

Recently, the introduction of targeted therapies has represented a relevant advance in the treatment of AML. Among them, venetoclax, an inhibitor of the BCL-2 protein, has been shown to improve clinical outcomes both in newly diagnosed patients and in those with refractory or relapsed disease. However, responses to this treatment are highly variable, and a significant proportion of patients exhibit primary resistance or develop secondary resistance, which limits its long-term efficacy.

In this context, a study led by Dr. Manel Esteller, head of the Cancer Epigenetics group at the Institut de Recerca Sant Pau (IR Sant Pau), analyzed whether epigenetic mechanisms could help explain this heterogeneity in therapeutic response. “We were interested in understanding why some tumors respond better than others to treatments such as venetoclax and whether epigenetics could help explain it,” notes Dr. Esteller. The work has been published in the journal British Journal of Haematology.

Epigenetics and Molecular Analysis of the Response to Venetoclax

Epigenetics studies changes that regulate gene activity without modifying the DNA sequence and allows the same genetic information to be expressed differently depending on the cellular context. Among the main epigenetic mechanisms is DNA methylation, a chemical mark that can silence gene expression and whose alteration has been associated both with cancer development and with responses to different oncologic treatments.

Based on this conceptual framework, the research team designed a large-scale study focused on integrating different layers of molecular information. To this end, they carried out an extensive computational biology analysis combining DNA methylation data, gene expression profiles, and drug response data in a collection of nearly 180 cell lines derived from leukemias, lymphomas, and other hematologic malignancies. This is an experimental model widely used for this type of systematic approach.

Approximately 850,000 DNA regions associated with epigenetic regulation were analyzed in this study, making it possible to generate a highly detailed map of genome-wide methylation patterns. These data were integrated with information on the expression levels of thousands of genes and with quantitative measures of drug response. “We wanted to go beyond analyzing a single gene or a single pathway, and that is why we integrated different levels of molecular information. This approach allowed us to identify epigenetic patterns associated with treatment response,” explains Dr. Esteller.

EIF5A2 as an Epigenetic Candidate Associated With Response to Venetoclax

The integrated data analysis identified a small set of genes whose epigenetic regulation showed a particularly consistent association with sensitivity to venetoclax. Among them, EIF5A2 stood out, as hypermethylation in its regulatory regions was reproducibly associated with reduced gene expression and with greater treatment efficacy.

EIF5A2 encodes a factor involved in the regulation of protein synthesis and in cellular processes that are fundamental for cell survival and proliferation. Although its involvement in different tumor contexts had been described previously, its potential role in responses to targeted therapies in AML had not been explored until now, giving this finding additional biological interest.

“The integrated analysis allowed us to prioritize genes with a solid association with treatment response, and EIF5A2 stood out not only because of its epigenetic profile, but also because it offered a clear functional hypothesis that could be tested in the laboratory,” explains Dr. Esteller. This reasoning was key to moving from computational identification of the candidate to its experimental evaluation.

Experimental Validation in Acute Myeloid Leukemia Models

The experiments consistently confirmed that EIF5A2 activity influences the response to venetoclax in cellular models of AML. Cell lines with hypermethylation of regulatory regions of this gene showed reduced RNA and protein levels and exhibited significantly greater sensitivity to treatment, whereas those in which EIF5A2 remained active tended to be more resistant.

“The bioinformatic prediction only made sense if it was experimentally confirmed, and it was crucial to show that loss of EIF5A2 activity was consistently associated with increased sensitivity to the drug,” explains Dr. Esteller. In addition, reactivation of gene expression using demethylating agents partially reversed this effect, reinforcing the direct relationship between epigenetic regulation, gene expression, and treatment response.

Taken together, these results establish a functional link between epigenetic regulation of EIF5A2 and venetoclax efficacy in experimental AML models, consolidating the biological validity of the findings obtained through computational analysis.

A Possible Mechanism Involved in Treatment Resistance

EIF5A2 encodes a protein that requires a highly specific chemical modification, known as hypusination, to be functional. This process depends on specific enzymes and on the availability of certain cellular polyamines, making this pathway a potentially relevant regulatory checkpoint from a biological standpoint.

Building on this knowledge, the researchers explored whether pharmacological inhibition of EIF5A2 activation could modify the response to venetoclax. In experimental models, combining venetoclax with a preclinical inhibitor of this process increased the sensitivity of initially resistant cells, while it did not produce an additional effect in cells that were already responsive to treatment.

These results suggest that EIF5A2 activity may play a relevant role in mechanisms of resistance to venetoclax and provide an initial functional insight into how this pathway could influence treatment efficacy.

Implications for Future Research

Although the study was conducted in experimental models and through retrospective analysis of available data, the authors emphasize that the results should be interpreted with caution. “This work does not change current clinical practice, but it provides a solid biological basis for further research on how to optimize the use of venetoclax and how to address treatment resistance in AML,” adds Dr. Esteller.

Overall, the study reinforces the value of epigenetic research in understanding variability in responses to oncologic treatments and lays the groundwork for future studies to evaluate these hypotheses in the context of controlled clinical trials. The goal is to advance toward increasingly personalized therapeutic approaches in hematologic diseases.

Reference Article:

Crespo-García E, Quero-Dotor C, Noguera-Castells A, Sancho-Vila L, Martinez-Verbo L, Esteller M. Epigenetic silencing and pharmacological inhibition of EIF5A2 foster venetoclax sensitivity in acute myeloid leukaemia. Br J Haematol 2026. https://doi.org/10.1111/bjh.70339

The Sant Pau Research Institute (IR Sant Pau) has been awarded a mobility grant under the Strategic Action in Health (AES) program, in its research staff mobility modality (M-AES), corresponding to the 2025 call, granted by the Instituto de Salud Carlos III (ISCIII). These grants aim to promote the advanced training of research staff through stays at leading international centers.

The grant has been awarded to Rafael Antonio Almendra-Pegueros, a predoctoral researcher who currently holds an active PFIS contract (Predoctoral Training in Health Research). As part of this mobility program, he will undertake a two-month stay at the :contentReference[oaicite:0]{index=0} (United Kingdom) from February 3 to April 3, 2026, with the aim of acquiring new technical and methodological skills to strengthen his research line at IR Sant Pau.

During the stay, the research project will focus on the identification of new therapeutic targets in aortic aneurysms, a severe cardiovascular condition for which there are currently no effective pharmacological treatments. The research is structured around two main scientific objectives.

On the one hand, the study will address abdominal aortic aneurysm (AAA) through in situ validation of differentially expressed genes previously identified in patients. At the University of Cambridge, advanced technologies such as RNAscope and imaging mass cytometry will be applied, enabling the analysis of multiple molecular markers in histological sections. These techniques will be used to validate genes related to processes such as endoplasmic reticulum stress, mitochondrial function, and inflammation, which are involved in AAA progression.

On the other hand, the research will focus on identifying new therapeutic targets to slow the progression of ascending thoracic aortic aneurysm (ATAA). In this case, different patient subgroups will be analyzed, including sporadic cases, patients with genetic syndromes such as Marfan or Loeys-Dietz syndrome, and patients with a bicuspid aortic valve. The work will combine transcriptomic analyses, qPCR techniques, protein panels, and functional validation studies to characterize the molecular mechanisms specific to each subgroup.

This line of research may contribute to the identification of prognostic biomarkers that could improve risk stratification, identify patients with a higher likelihood of aneurysm progression or rupture, and optimize surgical decision-making in clinical practice.

Once the stay is completed, the knowledge and techniques acquired will be integrated at IR Sant Pau. The project is embedded within the research lines of the Regulatory Mechanisms of Cardiovascular Remodeling group, coordinated by Dr. Cristina Rodríguez, and the Cardiovascular Biochemistry group, coordinated by Dr. José Luis Sánchez Quesada. These groups have the necessary equipment to continue the experimental work and broad access to human samples through collaboration with the Hospital de Sant Pau, the Banc de Sang i Teixits, and several clinical groups specialized in aortic pathology.

The research profile of Rafael Antonio Almendra-Pegueros, with a solid predoctoral track record and sustained scientific activity in the field of aneurysm pathophysiology, reinforces the value of this stay as a strategic training opportunity. It is also a source of scientific return for IR Sant Pau.

The Sant Pau Research Institute (IR Sant Pau) has secured funding for 16 health research projects in the Health Research Projects (PI25) call of the Carlos III Health Institute (ISCIII). These grants will make it possible to carry out competitive research over the next three years in different areas of biomedicine and clinical research, consolidating the institute’s research activity and strengthening its translational orientation.

The funded projects address relevant clinical problems and unmet medical needs, combining basic, clinical, and applied research. As a whole, they incorporate the study of biomarkers, new therapeutic approaches, clinical prediction tools, and strategies aimed at improving decision-making in healthcare delivery and public health.

Neurosciences and Mental Health

The PI25 call includes several projects in the field of neurosciences, addressing neurodegenerative diseases, cerebrovascular pathology, visual pathway disorders, and mental health from a translational perspective, integrating biomarkers, advanced neuroimaging, and new therapeutic approaches.

Within this framework, Dr. Daniel Alcolea leads a project focused on the pathological aggregation of alpha-synuclein, a key protein in synucleinopathies. The study will analyze this aggregation both in cerebrospinal fluid and in neuronal extracellular vesicles isolated from blood, with the aim of improving the in vivo diagnosis of dementia with Lewy bodies and mixed Alzheimer–Lewy forms. Correlating these biomarkers with cortical neuropathology and clinical profiles will make it possible to move toward more precise and less invasive diagnostic tools.

Research in stroke and brain injury is represented by two projects that address this area from different but convergent perspectives. Dr. Cristina Gallego Fabrega, through the TIME-ICH project, studies the temporal evolution of cerebral edema after intracerebral hemorrhage and its relationship with epigenetic mechanisms, particularly DNA methylation, with the aim of identifying prognostic biomarkers and potential therapeutic targets. For her part, Dr. Jara Cárcel Márquez leads the NeuroG3n project, which integrates three-dimensional genomics and chromatin accessibility analysis to identify genetic and regulatory mechanisms involved in post-stroke neurological deterioration.

In this same area, Dr. Elena Muiño Acuña is developing a project focused on CADASIL, a rare hereditary cerebrovascular disease with no specific treatment. The study aims to identify molecular biomarkers associated with disease progression and to evaluate drug repositioning strategies in cellular models to advance toward new therapeutic options for these patients.

In the field of autoimmune diseases of the central nervous system, Dr. Angela Vidal-Jordana coordinates a multicenter project focused on acute optic neuropathies, integrating serum biomarkers, neuroimaging techniques, and functional assessment of the visual pathway to improve etiological diagnosis between optic neuritis and non-arteritic ischemic optic neuropathies, as well as to predict visual prognosis from early stages of the disease.

The call also includes a project in mental health, led by Dr. Joaquim Soler Ribaudi. This project evaluates the effectiveness and feasibility of a psychotherapeutic intervention based on increasing non-comparative self-esteem for the secondary prevention of suicidal behavior in individuals with multiple previous attempts. The study proposes an approach that addresses the reduction of suicidal ideation by fostering improvements in baseline psychological well-being and quality of life, rather than solely responding to the acute crisis that precipitates a suicide attempt.

Autoimmunity and Neuromuscular Diseases

This section brings together projects focused on autoimmune diseases, with particular attention to neuromuscular disorders in which diagnosis and clinical stratification remain challenging.

In this context, Dr. Eduardo Gallardo Vigo leads a project focused on seronegative myasthenia gravis, a subgroup of patients without specific diagnostic biomarkers. This project will also be co-directed by Dr. Elena Cortés. The research aims to identify new immunological targets, validate their pathogenic role, and develop animal models that will allow a more profound understanding of disease mechanisms and optimization of therapeutic approaches.

Within this same framework, the team led by Dr. Luis Querol is developing a project aimed at the identification of new clinically relevant autoantibodies in autoimmune neuropathies, redefining the node of Ranvier as an immunologically active structure. This approach contributes to a more in-depth understanding of the immunopathogenic mechanisms involved and opens new avenues for the development of more precise diagnostic and therapeutic tools in autoimmune neuropathies.

Cardiology, Metabolism, and Cardiovascular Risk

In the cardiovascular field, the PI25 call includes projects that analyze risk from a molecular and systemic perspective, integrating genetic, metabolic, and inflammatory factors.

Dr. Teresa Padró Capmany leads a project focused on the molecular composition of lipoprotein(a) in patients with familial hypercholesterolemia. Using a systems biology approach, the study analyzes the relationship between the molecular characteristics of this lipoprotein, the progression of atherosclerosis, and cardiovascular risk, incorporating an analysis of biological sex differences.

Along these same lines, Dr. César Díaz Torné is leading a project that evaluates the clinical, inflammatory, and cardiovascular benefits of reducing monosodium urate crystal deposition in patients with gout. The study analyzes the impact of intensive urate-lowering therapy not only on joint symptoms but also on systemic inflammation and overall cardiovascular risk, a frequent comorbidity in these patients.

Precision Medicine and Complex Diseases

The PI25 call includes projects that share a precision medicine approach, based on the integration of clinical data, molecular analysis, and advanced technologies to address complex and heterogeneous diseases.

This section includes the project led by Dr. Astrid Crespo Lessmann, together with Dr. Vicente Plaza Moral, which combines metabolomics, microbiota, radiomics, clinical data, and artificial intelligence techniques to develop a predictive model of asthma exacerbations. The aim is to identify biomarkers in the context of an exacerbation that enable early identification of patients at risk of severe episodes and optimization of clinical follow-up.

Likewise, Dr. Lorena Alba Castellon leads a project focused on the tumor microenvironment of colorectal cancer, analyzing the role of PDGFRβ+ fibroblasts in drug response and immunotherapy and evaluating innovative strategies, such as the use of targeted nanotoxins, to overcome mechanisms of therapeutic resistance.

Women’s Health and Reproductive Medicine

In the area of women’s health, the call funds projects focused on highly prevalent conditions with a significant impact on maternal health and quality of life.

Dr. Elisa Llurba Olivé coordinates the Late-CARE project, co-led by Dr. Carmen Garrido, aimed at improving the prediction of late-onset preeclampsia through the integration of cardiovascular, angiogenic, inflammatory, and metabolomic biomarkers, with an approach oriented toward clinical practice.

In this same area, Dr. Taisiia Melnychuk Mykhaylevska leads the ENDO-GUT project, which evaluates the impact of a group dietary intervention in women with endometriosis. It analyzes its effect on quality of life and pain through improvements in systemic inflammation and the resulting changes in the microbiota. This provides evidence on non-pharmacological interventions that are easy to implement.

Population Health, Primary Care, and Environmental Health

The call also includes projects with a population health approach, aimed at improving clinical and public health decision-making in real-world settings.

Dr. Carlen Reyes Reyes, together with Dr. Carlos Brotons Cuixart, leads a project that combines population analysis and a clinical trial to develop a risk scale for adverse events associated with the prescription of potentially inappropriate medication in older adults. the goal is to evaluate the effect of a deprescribing intervention based on shared decision-making in primary care.

In the field of environmental health, Dr. Marta Roqué Figuls is developing a project focused on the impact of heat waves on health, especially in vulnerable populations. It also focuses on improving public health decision-making through the formulation of a methodological framework for synthesizing scientific evidence on environmental exposures related to climate change.

Research Oriented Toward Clinical Practice and Public Health

Overall, the 16 funded projects reflect the diversity of research lines at IR Sant Pau and its capacity to address health problems from different approaches—biomedical, clinical, population-based, and health systems—with a clear orientation toward knowledge transfer and the improvement of healthcare practice and public health.

A team from the Parkinson’s Disease and Movement Disorders Group at the Institut de Recerca Sant Pau (IR Sant Pau) and the Neurology Department of Hospital de Sant Pau has described in detail, for the first time, how visual perception is altered in people with Parkinson’s disease who experience hallucinations. The study, led by researcher Laura Pérez-Carasol and Drs. Javier Pagonabarraga and Saül Martínez-Horta, has just been published in npj Parkinson’s Disease, part of the Nature group, and provides one of the most comprehensive characterizations to date of the neurocognitive mechanisms underlying this phenomenon.

Visual hallucinations are one of the most frequent and clinically significant non-motor symptoms in Parkinson’s disease, even at early stages. They usually manifest as brief sensations of presence, figures that disappear when looked at directly, or shadows crossing the periphery of the visual field. They may also include very subtle illusions, such as attributing facial features to everyday objects. Although many individuals recognize that these perceptions are not real, their appearance indicates that the systems responsible for interpreting the environment are beginning to function with reduced precision. Numerous studies have shown that these early episodes increase the risk of developing cognitive impairment and of progressing toward more complex and persistent hallucinations.

According to Dr. Javier Pagonabarraga, “These early manifestations show us that the brain is already struggling to harmonize what it receives from the senses with the internal mechanisms that give meaning to experience. Even if the patient is fully aware that these perceptions are not real, they reflect an imbalance that may intensify over time.”

An Experiment That Makes It Possible to Observe How the Brain Builds —and Modifies— Perception

To understand which processes become dysregulated leading to hallucinations, the researchers studied 93 patients with Parkinson’s disease without dementia. Participants performed a visual categorization task in which they had to quickly decide whether an image corresponded to a face, an object, or an object that merely resembled a face, while their brain activity was recorded using electroencephalography. This methodology made it possible to observe, with high temporal precision, how the brain constructs a percept from its most basic stages through to interpretation and cognitive review.

The analyses showed that patients with hallucinations do not present alterations in vision or in the earliest stages of visual processing. The P100 signal, which reflects this initial phase, is normal across all groups, indicating that they perceive sharpness, contrast, or motion in the same way as individuals without hallucinations. Alterations emerge at later stages, when the brain must organize visual information and assign it meaning.

Detailed analysis of brain activity indicates that the first disruption appears during the structural encoding phase, when the brain interprets the shape of the stimulus and generates a recognizable representation. This activity, reflected in the N170 signal, is markedly reduced in patients with hallucinations, even in those without cognitive impairment. This reduction indicates that initial visual representations are built with less precision, lower internal clarity, and weaker structural robustness, forcing the brain to operate on a more ambiguous and vulnerable perceptual foundation.

In the words of Laura Pérez-Carasol, “This first alteration is essential to understanding everything that follows. If the initial visual representation is already weak or incomplete, the brain loses the stable reference on which it normally builds meaning. It is as if the image arrives ‘half-formed,’ opening the door for other internal signals to take on a greater role than they should.”

On this weakened perceptual base, a second mismatch occurs. Under normal conditions, the brain draws on prior knowledge—memories, learned associations, expectations—only when visual information is ambiguous. However, in patients with hallucinations, this mechanism is activated too early and with exaggerated intensity. The increase in the N300 signal indicates that the system attempts to complete perception prematurely, imposing internal meanings before visual information is fully available. This tendency is even more pronounced in patients with mild cognitive impairment, who rely more heavily on internal processes to interpret external stimuli.

The study also identifies a third alteration in the phase responsible for reviewing and correcting the generated interpretation. This stage, associated with the P600 signal, is weakened in patients with hallucinations, particularly in those who also present mild cognitive impairment. The reduction in P600 indicates a decreased capacity for cognitive monitoring, making it harder to correct interpretations that do not fit reality and facilitating the persistence and conviction of erroneous perceptions.

This chain of alterations—weakened structural encoding, premature semantic activation, and insufficient monitoring—explains why perception loses stability and becomes more prone to generating hallucinatory experiences. As Dr. Pagonabarraga summarizes, “What we see is a progressive loss of coordination between systems that should operate in a precise and sequential manner. When this harmony breaks down, perception ceases to be a stable process and becomes overly dependent on internal signals. That combination ultimately creates fertile ground for hallucinations to emerge.”

A Lack of Coordination With Major Clinical Implications

Beyond describing how hallucinations originate, the authors emphasize that the pattern of desynchronization between the different stages of visual processing provides valuable insight into the clinical course of the disease. The results prove that these perceptual alterations reflect a progressive shift in cognitive dynamics, particularly in individuals who are beginning to show mild cognitive impairment. This combination—perceptual fragility and cognitive fragility—defines a profile of heightened vulnerability, relevant both for understanding current symptoms and for anticipating future progression.

As Pérez-Carasol explains, “These early signals allow us to see that the brain begins to lose precision and coordination long before more obvious symptoms appear. If we understand this vulnerability from the outset, we can identify patients who will require closer follow-up and adapt interventions before symptoms become more disabling.”

Dr. Saül Martínez-Horta highlights that a clinical reading of these results could help transform care practice. “If we can detect these changes in perceptual and cognitive dynamics early on, we will be able to intervene sooner and tailor treatments and support strategies according to each patient’s profile.”

Overall, the study strongly suggests that visual hallucinations are part of a broader process of neurocognitive dysregulation, in which coordination between perception, meaning, and control becomes increasingly fragile. This pattern, more pronounced in patients with mild cognitive impairment, emerges as a clinically relevant indicator for defining risk groups and guiding personalized assessment and follow-up strategies.

An Advance That Opens New Avenues for Early Detection and Personalized Care

The authors note that having a detailed model of how different phases of perception are altered could transform the way non-motor symptoms of Parkinson’s disease are assessed. Identifying characteristic neurophysiological patterns—such as reduced N170, early enhancement of N300, or decreased P600—opens the door to the development of objective markers capable of detecting subtle changes before hallucinations become clinically evident or before more marked cognitive decline occurs.

For Dr. Javier Pagonabarraga, this approach represents a significant advance. “Understanding this sequence helps us explain hallucinations and allows us to identify early risk signals and propose more precise intervention strategies. We can begin to envision more refined assessments that combine clinical and neurophysiological measures to anticipate symptom onset and provide truly personalized care.”

In addition, the study reinforces the role of IR Sant Pau as an international reference center in research on non-motor symptoms of Parkinson’s disease. The work demonstrates that detailed analysis of perceptual mechanisms can yield key insights into disease progression and opportunities for intervention at early stages. This type of research, funded by the Fundació La Marató de TV3 and the Instituto de Salud Carlos III, defines a line of work aimed at developing advanced diagnostic tools and new therapeutic strategies. This is based on a fine-grained understanding of the brain processes underlying perception and cognition.

Reference Article:

Pérez-Carasol L, Martinez-Horta S, Horta-Barba A, Bejr-Kasem H, Marín-Lahoz J, Perez-Perez J, Aracil-Bolaños I, Pagonabarraga J, Kulisevsky J. Disrupted visual-to-semantic dynamics promote visual hallucinations in Parkinson’s disease. NPJ Parkinsons Dis 2025:1–15. https://doi.org/10.1038/s41531-025-01235-1.

The Institut de Recerca Sant Pau (IR Sant Pau) has secured funding for three research projects in the 2024 call for Knowledge Generation Projects from the Spanish State Research Agency, within the framework of the 2024–2027 State Plan for Scientific, Technical, and Innovation Research. Altogether, the projects have been awarded a total granted budget of €1,138,250. The grants will support the launch of new research lines in neuroscience, rare diseases, and cancer, as well as strengthen researcher training through two associated predoctoral contracts.

The awarded projects are led by Dr. Àlex Bayés, Dr. Jordi Surrallés, and Dr. Manel Esteller. They reflect the diversity and robustness of the research carried out at IR Sant Pau, combining high-level basic science with approaches that have strong translational potential.

The Knowledge Generation Projects program aims to foster excellent scientific research and advance knowledge across all fields, without a closed thematic orientation, promoting both fundamental research and research capable of laying the foundations for future applications. These grants are designed to strengthen the scientific system, support consolidated research careers, and promote the training of new research talent through predoctoral contracts associated with the funded projects.

New Insights Into the Functional Organization of the Brain

The project led by Dr. Àlex Bayés focuses on the study of neuronal synapses and brain oscillations as pillars of brain organization and function, with awarded funding of €250,000. In this context, the researcher emphasizes that “understanding how synapses and brain oscillations are coordinated is key to deciphering the basic principles of brain function,” placing the focus on how information is integrated at different scales, from connections between neurons to the coordinated activity of entire networks.

The research is based on the idea that brain function does not depend solely on isolated connections but on the interaction between synaptic mechanisms and oscillatory activity patterns that enable the temporal synchronization of neuronal circuits. This coordination, expressed in the form of rhythms and oscillations, acts as an organizing system for communication between brain regions and underpins complex cognitive and behavioral processes.

Through an integrative approach, the project explores the molecular and functional mechanisms that support synaptic architecture and its relationship with these global activity dynamics. The aim is to generate fundamental knowledge on how these communication systems are structured, maintained, and adjusted, providing a solid basis for interpreting what happens when they are disrupted in neurological and neuropsychiatric disorders.

Advances in Genomics and New Therapeutic Strategies in Fanconi Anemia

The project led by Dr. Jordi Surrallés addresses Fanconi anemia, a rare inherited disease characterized by genomic instability, bone marrow failure, and a high predisposition to cancer development, such as acute myeloid leukemia or head and neck tumors. The initiative has been awarded €425,375, enabling the combination of advanced genomics and functional analysis with a clear orientation toward clinical applicability.

The study focuses on improving diagnosis and functional characterization of the mutations involved in Fanconi anemia and on exploring pathways to translate this knowledge into innovative therapeutic strategies. In this regard, the project integrates analysis of DNA repair processes with approaches based on synthetic lethality, a strategy that allows selective elimination of tumor cells by exploiting specific vulnerabilities that do not affect healthy cells. It also includes the study of responses to targeted therapies.

As summarized by Dr. Surrallés, “the goal is for genomic and molecular knowledge to translate into concrete improvements for patients, both in diagnosis and in therapeutic options.” The project also includes a predoctoral contract, strengthening the training of research talent in a highly specialized field and consolidating IR Sant Pau’s leadership in the study of rare diseases and cancer predisposition syndromes. In addition, the project is supported by a postdoctoral contract and a technical profile, contributing to molecular genomics tasks and laboratory technical support.

Epigenetics and Immunotherapy to Optimize Cancer Treatment

The third project, led by Dr. Manel Esteller, focuses on the epigenetic and epitranscriptomic characterization of cancer immunotherapies, both cellular—such as CAR-T, CAR-NK, and tumor-infiltrating lymphocytes—and pharmacological, particularly immune checkpoint inhibitors. Under the acronym EPIMMUNOMICS and with funding of €462,875, the study applies single-cell technologies that enable analysis of molecular properties at the individual cell level, together with multi-omics analyses, to understand the mechanisms that determine response or resistance to these treatments.

The research addresses one of the main current challenges in oncology: explaining why immunotherapy, despite its transformative impact, does not benefit all patients. In this context, Dr. Esteller emphasizes that “understanding the epigenetic mechanisms that regulate the immune response is essential to expand the benefit of immunotherapy and make it more effective and personalized,” highlighting the need to identify biological signals that allow treatment response to be anticipated.

The project examines in detail the epigenome and epitranscriptome of tumor and immune cells to identify predictive biomarkers and new therapeutic vulnerabilities, with the aim of optimizing patient selection and contributing to the design of more precise therapeutic strategies. The initiative also includes a predoctoral contract, reinforcing the project’s training dimension and its medium- and long-term impact. In addition, the project plans to strengthen the team with profiles specialized in computational analysis to provide additional support for the exploitation of multi-omics data.

Boosting Research and Talent Training

With the award of these three projects, IR Sant Pau strengthens its capacity to attract competitive funding and to develop excellent research in key areas of biomedicine. At the same time, the incorporation of researchers in training helps ensure continuity and generational renewal in strategic research lines, consolidating the center’s commitment to knowledge generation and its transfer to society.

The Institute for Research Sant Pau (IR Sant Pau) has held a new edition of its Research Day, an annual event that consolidates the center as a leading reference in biomedical research and innovation at the service of health. The event, held in the auditorium of Hospital de Sant Pau, brought together researchers, healthcare professionals, institutional representatives, and experts from the research system to reflect on the major challenges and opportunities of hospital-based research.

The day was opened by Dr. Jordi Surrallés, Scientific Director of the IR Sant Pau, who welcomed attendees. Dr. Surrallés framed the meeting within the rollout of the 2025–2030 Strategic Plan, the year in which the strategic reflection initiated in recent years begins to translate into action and to transform the way IR Sant Pau operates. In his address, Dr. Surrallés also emphasized that «research cannot turn its back on society. Generating excellent knowledge is essential, but it is not enough: explaining what we do, why we do it, and what impact it has is part of our responsibility as a public research institution».

The Role of Philanthropy in the Biomedical Research Ecosystem

One of the first axes of the day was a discussion on the role of philanthropy in building the biomedical research ecosystem, with a lecture focused on analyzing how philanthropic support can make a decisive contribution to research development, especially in areas of high scientific and social impact.

The lecture was delivered by Àngel Font, Associate Director of Research and Fellowships at the “la Caixa” Foundation and Executive Director of the CaixaResearch Institute, who explained how the foundation provides sustained support for scientific and biomedical research, positioning it as a strategic priority. In this context, Font presented the CaixaResearch Institute as an example of how philanthropy can strengthen research excellence, foster collaboration between centers, and contribute to consolidating a competitive and sustainable research ecosystem, also at the European level.

This was followed by a roundtable discussion moderated by Dr. Jordi Surrallés and focused on the challenges and opportunities of hospital research institutes, with the participation of Dr. Begoña Benito, Director of the VHIR; Dr. Gabriel Capellá, Director General of the IDIBELL; Dr. Jordi Barretina, Director General of the IGTP; and Dr. Antoni Plasencia, Director General for Research and Health Innovation at the Department of Health of the Government of Catalonia. During the discussion, key issues were addressed such as the sustainability of research institutes, talent attraction and retention, and the need to strengthen environments that facilitate research excellence integrated within hospitals.

Independent Clinical Research in the Spotlight

The central session of the morning was devoted to the value of independent clinical drug research, with the presentation of several academic clinical trials led by IR Sant Pau and funded through the Independent Clinical Research (ICI) call of the Instituto de Salud Carlos III. This session featured, among others, a multicenter, randomized, double-blind trial with donepezil in mild cognitive impairment associated with Parkinson’s disease; the AFAN trial, focused on repositioning afatinib in oral cancer in patients with Fanconi anemia; a study on the antidepressant effects of psilocybin analyzed through functional neuroimaging; the LESS-AD trial, with levetiracetam to prevent epileptic seizures in adults with Down syndrome and Alzheimer’s disease; several trials with academic CAR-T cells in hematologic neoplasms; and the SAVE trial, which compares sevoflurane and propofol in general anesthesia in patients with ischemic stroke treated with endovascular therapies.

This set of presentations highlighted IR Sant Pau’s role in the development of academic and multicenter clinical trials, with a clear translational orientation. In the words of Dr. Surrallés, «Sant Pau’s distinctive feature is the ability to integrate disciplines, connect basic and clinical research, and always keep the focus on the patient».

New Leadership for Translational Research

The day continued with a session dedicated to new leadership in translational research, led by early-career researchers with emerging trajectories linked to competitive national investigator stabilization programs. This session showcased projects addressing some of the major current challenges in biomedical research from a clearly translational perspective.

Specifically, initiatives were presented focusing on the application of data science to integrate environmental, infectious disease, and clinical data in health research; on modulating the tumor microenvironment to improve therapeutic outcomes in solid tumors; on integrating omics, clinical, and epidemiological approaches in women’s health; on advancing neuropsychological assessment in people with Down syndrome in the digital era; and on developing precision psychiatry strategies based on brain circuits.

This session reinforced IR Sant Pau’s commitment to scientific talent development and to creating opportunities for new generations of researchers to lead high-impact projects. As emphasized by the Institute’s Scientific Director, «the Strategic Plan places talent, career paths, and organizational culture at the center, because there is no research excellence without teams that are supported, recognized, and have a future perspective».

Research Explained in Four Minutes

One of the main new features of this edition of the Research Day was the first-time inclusion of the outreach activity “240 seconds: my thesis in a flash”, which closed the day in the afternoon. This initiative gave prominence to doctoral candidates, who were challenged to explain their research orally in a maximum of four minutes, using clear, accessible language understandable to a non-specialist audience.

The activity was conducted in a format of consecutive short presentations, in which participants had to synthesize the objectives, methodology, and relevance of their research, emphasizing its application and potential impact. With this dynamic format, the session highlighted young researchers’ communication skills and contributed to bringing the research carried out at IR Sant Pau closer to the center’s scientific community and to society as a whole.

Immune Neoplasms and Targeted Therapies

The closing lecture of the morning block was delivered by Dr. Ari Melnick, Director of the Josep Carreras Leukaemia Research Institute, who presented a talk focused on pathogenesis and targeted therapies in immune neoplasms.

In his presentation, Dr. Melnick addressed the molecular and immunological mechanisms involved in the development of these diseases, as well as recent advances in targeted therapies and their translational potential in clinical practice, highlighting how mechanistic knowledge is opening the door to increasingly specific and personalized treatments in the field of hematologic neoplasms.

The day concluded with an institutional closing ceremony with the participation of Dr. Adrià Comella, Managing Director of Hospital de Sant Pau, and Dr. Jordi Surrallés, Scientific Director of IR Sant Pau, during which reflections were shared on the present and future challenges of hospital-based research. With this new edition of the Research Day, IR Sant Pau reaffirms its commitment to scientific excellence, independent research, and knowledge transfer, consolidating its position as a key player within the biomedical research system and as a driver of continuous improvement in healthcare. In his closing message, Dr. Surrallés recalled that «2025 is not an endpoint. It is a starting point. The challenge now is to consolidate the transformation, stay the course, and do it together».

Researcher Alejandra Pérez, a nursing professional affiliated with the Sant Pau Research Institute (IR Sant Pau), has been awarded a grant from the Official College of Nurses of Barcelona (COIB) to develop a research project focused on the assessment of quality of life in premature infants or those with low birth weight for gestational age, as well as that of their families, enrolled in the Neonatal Home Care Program (PADN).

The main objective of the project is to design and validate a specific scale that allows for rigorous measurement of quality of life in this care setting, a key dimension for assessing the real impact of care beyond traditional clinical indicators. At present, there are no validated instruments specifically designed to assess the quality of life of these infants during home follow-up after hospital discharge.

“Neonatal home care has demonstrated clear clinical benefits, but we still have very few tools that allow us to assess how infants and their families experience this stage,” explains Alejandra Pérez. “Having a validated scale will help us systematically incorporate quality of life as a relevant indicator in the evaluation of these programs and in the improvement of care.”

The research is structured in several complementary phases. First, a systematic review of the scientific literature will be conducted to identify the components that define the quality-of-life construct in premature infants and those with low birth weight. The project will then incorporate a qualitative study with a phenomenological approach, based on in-depth interviews with families enrolled in the PADN, with the aim of exploring their experiences and perceptions regarding their children’s quality of life and the family environment.

Based on these findings, the scale will be designed and subsequently undergo psychometric validation, involving expert participation and statistical analysis of its reliability and validity. This process will result in a specific, robust tool applicable to clinical practice, aimed at improving the assessment and follow-up of infants cared for in neonatal home hospitalization programs.

The project involves a research team composed primarily of nursing professionals, with the participation of neonatology specialists, and it addresses ethical and confidentiality aspects transversally, with the corresponding review by a research ethics committee. It also includes a detailed work plan and a dissemination strategy designed to facilitate the transfer of results to both clinical practice and the scientific community.

The awarding of this grant strengthens the role of nursing research at IR Sant Pau and its commitment to projects that place patients and their families at the center of health care, promoting a more comprehensive and humanized evaluation of care.

The Institut de Recerca Sant Pau (IR Sant Pau) has led a multicenter study showing that incorporating the biomarker NT-proBNP, commonly used to assess cardiac function, significantly improves the ability of the angiogenic sFlt-1/PlGF ratio to predict preeclampsia in the short term. The study, published in Clinical Chemistry, demonstrates that integrating both biomarkers makes it possible to refine risk stratification in women with clinical suspicion of the disease.

Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of maternal–fetal morbidity worldwide. The sFlt-1/PlGF ratio allows the disease to be ruled out when values are below 38, but above 38 its interpretation becomes less conclusive and requires close follow-up and additional assessments. The main challenge lies in managing cases with an sFlt-1/PlGF ratio between 38 and 84, where diagnostic and management uncertainty is greatest. As explained by Dr. Carmen Garrido, clinical head of Obstetrics at Hospital Sant Pau and collaborating researcher in the Perinatal and Women’s Medicine group at IR Sant Pau, “It is in this intermediate diagnostic range where NT-proBNP provides an additional answer that allows us to guide both the case and follow-up much more effectively.

How the Study Was Designed and What Each Predictive Model Contributed

To assess the added value of NT-proBNP, the team developed three predictive models based on different thresholds of the angiogenic ratio. The first re-evaluated cases with values above 38 by incorporating the cardiac biomarker. The second examined its usefulness at values above 85, traditionally associated with higher clinical risk. The third focused exclusively on the 38–84 range, an interval that is particularly complex from a diagnostic standpoint. This last model showed the most robust performance, as it made it possible to better discriminate between patients who would progress to preeclampsia and those who would not, improving short-term prediction of the disease.

According to Dr. Carmen Garrido, “These models allowed us to clearly identify the situations in which NT-proBNP provides decisive information, especially when the angiogenic ratio alone does not resolve the diagnostic uncertainty.”

To determine the clinical applicability of these models, the study assessed their performance across different clinical scenarios of preeclampsia: early-onset (before 34 weeks), preterm (before 37 weeks), term (after 37 weeks), and cases with maternal or fetal complications. This approach made it possible to verify whether the benefit of combining markers was maintained across all contexts or was particularly notable in specific profiles. According to Dr. Madalina Nicoleta Nan, staff biochemist at Hospital Sant Pau and researcher in the Perinatal and Women’s Medicine group, “Stratification by clinical scenario allowed us to confirm that combining NT-proBNP with the angiogenic ratio is especially valuable in predicting early-onset preeclampsia and higher-risk forms, where disease progression can accelerate in a very short time.”

The Combination of Markers Improves Prediction and Reduces Clinical Uncertainty

The study, conducted in 316 women with clinical suspicion of preeclampsia and based on the analysis of 424 samples, shows that NT-proBNP levels are significantly elevated in those who will develop preeclampsia within the following seven days. Integrating this biomarker with the angiogenic ratio maintains a negative predictive value of 99.5%, while improving the positive predictive value. This increases from 35.4% when using the sFlt-1/PlGF ratio alone to 60.7% for predicting early-onset preeclampsia one week before the appearance of clinical manifestations. This combination provides high reliability for ruling out the disease in the short term and makes it possible to prioritize surveillance for cases that are truly likely to progress.

In addition, the combination adds a complementary pathophysiological dimension: the angiogenic ratio reflects placental dysfunction, while NT-proBNP provides information on the degree of maternal cardiovascular stress, a factor closely linked to the risk of clinical deterioration. “Combining markers that inform on different processes,” explains Dr. Garrido, “helps us more precisely identify the patients who need intensified follow-up and avoid unnecessary interventions in those who do not.”

The usefulness of NT-proBNP is particularly evident in cases where the angiogenic ratio shows intermediate values and its diagnostic capacity is more limited. As detailed by Dr. Garrido, “NT-proBNP allows us to distinguish whether we are dealing with a patient at real risk of progression or whether a less intensive monitoring approach can be considered,” information that is essential for tailoring clinical decisions more accurately.

A Tool That Helps Anticipate Severe Complications

The analysis carried out in the study reveals that combining both biomarkers also makes it possible to anticipate complications and predict short-term clinical evolution. Women with abnormal values in both markers show a mean latency to delivery of 1.3 weeks, indicating closer proximity to decompensation and the need to intensify surveillance and prepare interventions in advance.

As highlighted by Dr. Madalina Nicoleta Nan, “When both markers are elevated, progression toward the need to end the pregnancy is usually faster, and having this information allows us to plan care more effectively.” Conversely, she adds, “If the angiogenic ratio is high but NT-proBNP remains low, this usually reflects placental alteration that does not imply preeclampsia requiring imminent delivery, allowing us to avoid hasty interventions.”

A Complementary, Accessible, and Easy-to-Implement Biomarker

The research team emphasizes that NT-proBNP does not replace the angiogenic ratio but rather complements it by providing relevant clinical information in cases where sFlt-1/PlGF is inconclusive. This complementarity facilitates more precise decision-making, allows follow-up to be tailored according to risk profile, and offers a high-value tool for clinical practice. In addition, NT-proBNP is an accessible, low-cost, and widely available test, which would facilitate its incorporation into care protocols.

Although the results need to be validated in larger and more diverse cohorts, they represent a significant advance in the early prediction of preeclampsia and open the door to multimarker diagnostic strategies with greater precision and real-world applicability. IR Sant Pau thus consolidates its leadership in perinatal research and in the development of diagnostic tools aimed at safer and more personalized care.

Reference Article:

Garrido-Giménez C, Nan MN, Cruz-Lemini M, García-Manau P, Garcia-Osuna Á, Ullmo J, Mora J, Sánchez-García O, Medina-Mallén MDC, Chóliz M, Platero J, Llurba E, EuroPE Working Group. Can NT-proBNP enhance the accuracy of angiogenic factors in the short-term prediction of preeclampsia? Clin Chem 2025;72:206–16. https://doi.org/10.1093/clinchem/hvaf135

The Sant Pau Research Institute (IR Sant Pau) has received funding from the Carlos III Health Institute (ISCIII), co-funded by the European Union through European Funds, for the technological development of OptimAP. This project is aimed at improving the use of antibiotics in acute respiratory infections in children seen in primary care.

The grant is part of the 2025 call for Health Technology Development Projects within the Strategic Action in Health (AES). Its objective is to accelerate the transfer of research results to the healthcare system and to promote innovative solutions with a real impact on clinical practice.

Acute respiratory infections are one of the leading reasons for pediatric consultations and a frequent cause of antibiotic prescribing, often unnecessarily. This situation contributes to the rise of antimicrobial resistance, one of today’s major public health challenges. In this context, OptimAP proposes an innovative intervention to reduce unnecessary antibiotic prescribing without compromising safety or quality of care.

The project is led by Dr. Pablo Alonso Coello, head of the Clinical Epidemiology and Health Services research group at IR Sant Pau, and combines two complementary strategies: a communication skills training program for primary care professionals and a digital tool aimed at families, designed to improve understanding of respiratory infections and to facilitate shared decision-making.

The development of OptimAP, including its evaluation through a clinical trial under real-world clinical practice conditions, was previously funded thanks to a grant from La Marató de TV3. The results demonstrated a significant reduction in antibiotic use with no increase in complications or loss of family satisfaction.

With the current funding, totaling €147,620, the project will focus on final validation, technological optimization, and the assessment of the tool’s clinical, organizational, and economic impact. It will also focus on the analysis of regulatory and feasibility aspects to facilitate its implementation and scalability within the healthcare system.

Through this initiative, IR Sant Pau strengthens its commitment to the development of innovative solutions that contribute to more rational antibiotic use and to the fight against antimicrobial resistance in pediatric primary care.

A multidisciplinary team has uncovered a key mechanism that allows the human bacterium Mycoplasma pneumoniae—responsible for atypical pneumonia and other respiratory infections—to obtain cholesterol and other essential lipids directly from the human body. The discovery has been published in Nature Communications. The research was co-led by Dr. Noemí Rotllan, from the Sant Pau Research Institute (IR Sant Pau) and the Center for Biomedical Research in Diabetes and Associated Metabolic Disorders (CIBERDEM); Dr. Marina Marcos, from the Autonomous University of Barcelona (UAB); and Dr. David Vizarraga, from the Institute of Molecular Biology of Barcelona of the Spanish National Research Council (IBMB-CSIC) and the Center for Genomic Regulation (CRG). Overall coordination was led by Dr. Joan Carles Escolà-Gil, from IR Sant Pau and CIBERDEM; Dr. Jaume Piñol, from UAB; and Dr. Ignacio Fita, from IBMB-CSIC. The study also involved collaboration from the Institute of Biotechnology and Biomedicine of the UAB (IBB-UAB), the Center for Biomedical Research in Cardiovascular Diseases (CIBERCV), and other leading institutions.

Dr. Joan Carles Escolà-Gil explains that “the bacterium uses the P116 protein as a highly effective tool to capture cholesterol and other essential lipids from the host, a mechanism that allows it to survive and colonize tissues beyond the lung.” He adds that “understanding this process opens new avenues to block its growth and to explore biotechnological applications based on its affinity for lipid-rich tissues.”

This discovery is particularly relevant because Mycoplasma pneumoniae is primarily known as a respiratory bacterium, yet several studies—including this one—show that it can reach other tissues in the body, especially those with a lipid-rich environment. Understanding how it achieves this extra respiratory colonization helps explain clinical manifestations outside the lung and provides clues about its potential contribution to systemic inflammatory processes.

P116, a Bacterial System for Cholesterol Uptake

Unlike other bacteria, Mycoplasma pneumoniae cannot synthesize many lipids that are essential for the integrity of its membrane, including cholesterol, and therefore depends entirely on the host to survive. In this context, the new study demonstrates that the P116 protein acts as a highly efficient lipid uptake system, capable of extracting cholesterol and other lipid species from both human lipoproteins—including LDL and HDL—and different cell types.

Experiments conducted by the team show that P116 rapidly incorporates cholesterol from LDL and HDL but can also capture phosphatidylcholines, sphingomyelins, and triacylglycerols. This ability to recognize and absorb multiple types of lipids makes P116 an essential mechanism for the survival of the microorganism. By supplying its membrane with components obtained directly from the host, Mycoplasma pneumoniae can adapt to different environments in the body and colonize tissues with a high lipid content beyond the respiratory system.

Dr. Noemí Rotllan highlights the biological significance of this finding: “P116 acts as a lipid entry gate for the bacterium, an extraordinarily versatile system that allows it to incorporate cholesterol, phospholipids, and sphingolipids from the host.” She adds that “this broad lipid uptake capacity largely explains why Mycoplasma pneumoniae can survive in such diverse environments and localize to tissues where other bacteria would not be able to thrive.”

An Antibody That Slows Growth and Adhesion

The study also reveals that a monoclonal antibody specifically directed against the C-terminal domain of P116 markedly blocks cholesterol uptake by the bacterium, a process essential for its survival. “By preventing P116 from functioning as a lipid entry system, the antibody significantly reduces the growth of Mycoplasma pneumoniae in cell cultures and limits its ability to adhere to human atherosclerotic lesions in ex vivo samples. This dual action—slowing bacterial proliferation and preventing its presence in vulnerable areas of the cardiovascular system—represents a major advance in understanding the pathogenic and extra respiratory role of this microorganism,” notes Dr. Marina Marcos, a researcher at UAB.

The researchers emphasize that preventing this adhesion is particularly relevant because the presence of Mycoplasma pneumoniae in vulnerable plaques could promote local inflammation and compromise lesion stability. Unstable plaques are more prone to rupture, a process that can trigger serious cardiovascular events.

Dr. Joan Carles Escolà-Gil underscores its potential: “The antibody targets the bacterium’s key point, which is its ability to capture cholesterol. By blocking P116, we slow its growth and prevent it from adhering to atherosclerotic lesions.” He adds that “this is relevant because the presence of Mycoplasma pneumoniae in vulnerable plaques could contribute to inflammation and compromise their stability. Preventing this adhesion offers an opportunity to further protect tissues affected by atherosclerosis.”

A Biotechnological Tool to Target Therapies

The researchers have also used a modified and harmless form of the bacterium, designed to serve as a biotechnological tool to study how it distributes within the body. This version of the microorganism retains its natural ability to localize to lipid-rich tissues but has been adapted so that it does not cause disease. In experiments with hypercholesterolemic mice, the modified bacterium selectively accumulates in the liver and in atherosclerotic plaques, making it a potential vehicle for delivering therapeutic molecules or diagnostic agents precisely to the tissues where they are most needed.

This capacity for specific targeting opens a promising avenue in an emerging area of biotechnology: the use of modified living microorganisms as systems for targeted delivery of therapeutic molecules. In the case of Mycoplasma pneumoniae, its minimalist metabolism and dependence on host lipids make it particularly attractive as a manipulable and safe platform.

Dr. Noemí Rotllan summarizes it as follows: “The modified version of Mycoplasma pneumoniae shows a natural tropism toward the liver and atherosclerotic lesions, making it a promising biotechnological platform for the study and treatment of metabolic and cardiovascular diseases.” She adds that “leveraging the biology of this microorganism in a controlled way allows us to envision targeted therapeutic strategies that are more precise and potentially more effective for acting on tissues affected by atherosclerosis or fatty liver disease.”

A Conceptual Advance and a Top-Level Scientific Collaboration

Beyond its biomedical relevance, the study provides a conceptual advance in understanding Mycoplasma pneumoniae, a pathogen with one of the smallest known bacterial genomes, which depends heavily on the host to obtain essential lipids. Identifying P116 as a fundamental mechanism of lipid uptake opens new avenues for the development of antimicrobial therapies and vaccines.

Scientists from the Joint Electron Microscopy Center at the ALBA Synchrotron, the University of Navarra Clinic, and the Navarra Health Research Institute (IdiSNA) also participated in the research. They contributed to the structural characterization of P116, the analysis of its interaction with antibodies, and imaging and biodistribution studies in animal models.

The work strengthens a multidisciplinary scientific collaboration among leading centers in structural biology, microbiology, cardiometabolism, and biomedical imaging. It places this line of research at the forefront of the design of new biotechnological tools based on modified microorganisms to study and intervene in metabolic and cardiovascular diseases.

Reference Article:

Vizarraga D, Marcos M, Rotllan N, Martín J, Santos D, Camacho M, Soto B, Velasco-Reniu L, Guerra P, Pareja F, Collantes M, Wu W, Rodríguez-Arce I, Serrano L, Piñol J, Fita I, Escolà-Gil JC. Sources of essential lipids for Mycoplasma pneumoniae via P116 to target liver and atherosclerotic lesions. Nat Commun 2025;16:11159. https://doi.org/10.1038/s41467-025-66129-5

The Institut de Recerca Sant Pau (IR Sant Pau) has been awarded three research activity intensification grants in the 2025 call of the Instituto de Salud Carlos III (ISCIII). This program is aimed at healthcare professionals with an established scientific track record and seeks to relieve their clinical workload partially so they can devote a greater proportion of their time to research, without compromising patient care.

These grants make it possible to more closely integrate research into clinical practice, fostering the development of projects focused on improving the diagnosis, treatment, and prognosis of highly complex diseases. In this edition, the grant recipients are Dra. Ana Aulinas, Dr. Luis Prats Sánchez, and Dr. Ricardo Rojas-García, whose projects represent strategic areas of biomedical research at IR Sant Pau.

Dra. Ana Aulinas, a specialist in endocrinology and nutrition, focuses her research activity on hypothalamic and pituitary disorders, a group of rare conditions characterized by low prevalence and high diagnostic and therapeutic complexity. Dra. Aulinas coordinates the Functional Unit for Pituitary Disorders, a multidisciplinary unit that operates within the European Reference Network on Rare Endocrine Conditions (EndoERN). The unit is nationally recognized as a CSUR center for the diagnosis and treatment of complex pituitary disorders and is part of the XUEC for rare endocrine diseases. Thanks to this grant, she will be able to combine patient care for pituitary disorders with clinical and translational research in this field, within the framework of project PI24/01428. This project focuses on the study of comorbidities associated with hypothalamic damage and hypopituitarism and their relationship with the neurohormone oxytocin. In this way, IR Sant Pau’s participation is strengthened in projects aimed at improving the diagnosis and treatment of hypothalamic and pituitary diseases, as well as the quality of life of affected individuals.

Dr. Luis Prats Sánchez, a neurologist, is a member of the IR Sant Pau research group on cerebrovascular diseases and actively participates in the RICORS-ICTUS network. His work focuses on hemorrhagic stroke, with particular interest in the mechanisms that determine clinical outcomes and neurological recovery. With the support of this intensification grant, he will be able to expand his dedication to translational research and consolidate projects such as END-GROWTH (PI24/01009), which will compare best medical therapy with and without endovascular treatment. This will determine which strategy best predicts hematoma growth in patients with spontaneous intracerebral hemorrhage.

Meanwhile, Dr. Ricardo Rojas-García, consultant physician in the Department of Neurology, will carry out his work within the framework of project PI23/00845, focused on amyotrophic lateral sclerosis (ALS). This intensification allows him to combine clinical activity with research in neuromuscular and neurodegenerative diseases, strengthening IR Sant Pau’s participation in studies that apply molecular biology and biomarker analysis to improve understanding of the disease. His expanded dedication will help advance clinical research in ALS and generate results with the potential for direct impact on the care of affected individuals.

The awarding of these three intensification grants reinforces IR Sant Pau’s commitment to applied clinical research and the promotion of clinical scientific talent. These projects, developed in close collaboration with the services of Hospital de Sant Pau, will contribute to generating knowledge that directly translates into improved patient care and advances in translational medicine.

The Sant Pau Research Institute (IR Sant Pau) will lead two new independent clinical trials in areas of high clinical complexity—hematologic oncology and acute ischemic stroke—after securing more than €2.5 million in competitive public funding through the 2025 Independent Clinical Research Projects (ICI) call of the Carlos III Health Institute (ISCIII). Both studies will be conducted in the hospital setting and address unmet clinical needs, with the aim of generating robust scientific evidence to improve the therapeutic management of patients with severe, high–public health–impact diseases.

The projects, promoted from the academic sphere and with no commercial interest, are aligned with a model of independent clinical research designed to answer questions that are relevant to clinical practice. This approach enables the generation of knowledge that is directly applicable to the clinical setting, reduces variability in therapeutic decision-making, and contributes to more precise, evidence-based medicine.

A New Academic CAR-T Therapy for Patients With Refractory Hodgkin Lymphoma

One of the funded projects is led by Dr. Javier Briones, director of the Oncology Hematology and Transplant Research Group at IR Sant Pau and director of the Hematology Department at Sant Pau Hospital, with total funding of €1,805,657.59. Through a phase I/II clinical trial, the study will evaluate a fourth-generation academic CAR-T therapy developed entirely at Sant Pau for the treatment of patients with refractory classical Hodgkin lymphoma. This population has a particularly poor prognosis after failure of available therapies.

The cellular therapy, known as HSP-CAR30-CCR200, incorporates an innovative design aimed at counteracting tumor inhibitory mechanisms that limit the effectiveness of current CAR-T therapies and promote loss of response over time. The trial will assess treatment safety and its ability to induce deeper and more durable antitumor responses, with the goal of expanding therapeutic options for patients who currently have very limited alternatives.

Dr. Briones emphasizes that “this trial arises from the need to offer new therapeutic options to patients with Hodgkin lymphoma who no longer respond to available treatments; the study builds on the previous trial, a European pioneer, that we conducted with CART30 at our center. This new study allows us to introduce design improvements that increase its effectiveness and to evaluate its potential in a real-world clinical setting, with the ultimate goal of achieving more durable and clinically meaningful responses.”

This project builds on Sant Pau’s prior experience in the development of academic CAR-T therapies, integrating preclinical research, manufacturing of the cellular medicinal product in hospital facilities accredited according to international quality and safety standards, and its subsequent clinical evaluation in patients. This enables a rapid and safe translation from the laboratory to clinical practice.

Maximizing the Benefit of Thrombectomy in Ischemic Stroke Through Selection of the Optimal Anesthetic Protocol

The second awarded project, with total funding of €765,704.94, is led by Dr. Pol Camps, coordinator of the Cerebrovascular Diseases Group at IR Sant Pau and of the Stroke Unit at Sant Pau Hospital. It focuses on the management of acute ischemic stroke. The SAVE study is a multicenter clinical trial that will compare two general anesthesia strategies—sevoflurane and propofol—in patients undergoing mechanical thrombectomy, the standard-of-care treatment for the most severe strokes.

Although mechanical thrombectomy has represented a decisive advance in stroke treatment, important questions remain regarding optimal anesthetic management during the procedure and its impact on subsequent neurological outcomes. The trial will evaluate variables such as final cerebral infarct volume, functional recovery, and procedure safety, with the aim of providing evidence to optimize and standardize clinical protocols.

From a clinical care perspective, Dr. Camps notes that “thrombectomy has transformed the prognosis of acute ischemic stroke, but there are still aspects of the procedure that can influence clinical outcomes. This study seeks to generate solid evidence to determine the most appropriate anesthetic strategy and to help maximize the benefit of this treatment for patients who experience an ischemic stroke.”

The project will be carried out in collaboration with several public healthcare system hospitals, enabling the recruitment of a representative number of patients and ensuring the robustness of the results. Its multicenter design and practical orientation confer a high potential for immediate translation into clinical practice, with a direct impact on clinical decision-making and on the care of patients with acute ischemic stroke.

Independent Clinical Research Focused on Clinical Practice

With the launch of these two trials, IR Sant Pau strengthens its commitment to independent clinical research, driven from the public and academic sectors and focused on addressing clinically relevant questions for the healthcare system. This model makes it possible to generate high-value-added knowledge and to effectively translate it into the care setting, contributing to improvements in the quality, safety, and efficiency of patient care.

The Department of Health has awarded three grants under the PERIS 2025 program to intensify research activity to professionals from the Sant Pau Research Institute (IR Sant Pau). Each initiative will receive €149,760, representing a total investment of €449,280 aimed at promoting research lines that may transform the diagnosis, monitoring, and management of various neurological diseases.

PERIS strengthens research carried out within the healthcare system and enables professionals who combine clinical practice and research to have protected time to advance priority projects. In this call, the three proposals from IR Sant Pau focus on strategic areas for public health: the early detection of neurodegenerative diseases, improved diagnosis of rare disorders, and the management of a particularly relevant complication in Down syndrome.

Characterization of the Early Phases of the Alzheimer–Lewy Spectrum

One of the supported research lines focuses on understanding what happens in the brain long before symptoms of diseases such as Alzheimer’s disease or dementia with Lewy bodies become evident. The work led by Dr. Daniel Alcolea is based on an ambitious goal: to accurately describe the earliest phases of neurodegeneration and to understand how the pathological process begins. The study places particular emphasis on this initial phase—known as the prodromal stage—in which the brain already begins to undergo changes even though the individual has not yet developed symptoms.

To characterize this stage, the team combines multiple complementary sources of information, including cerebrospinal fluid and plasma biomarkers, recordings of brain activity, sleep studies, and high-resolution magnetic resonance imaging. This multimodal approach provides a comprehensive view of the process that precedes cognitive decline and makes it possible to identify patterns that would not be detectable using a single technique.

The project is structured in three successive phases that include the validation of cerebrospinal fluid and plasma biomarkers, the study of cohorts with differentiated biochemical profiles, and the integration of functional and imaging data. The ultimate goal is to build a reliable map of this silent yet decisive period, with the capacity to improve diagnostic stratification and lay the groundwork for future preventive or therapeutic interventions.

Plasma and Imaging Biomarkers for the Diagnosis of 4R Tauopathies

Another funded proposal addresses a key challenge in neurodegeneration: advancing early molecular diagnosis of the two main 4R tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Although they are often considered “rare” diseases, together they represent a frequent cause among patients who seek care for cognitive, behavioral, and motor impairment once Alzheimer’s disease has been ruled out.

At present, these diseases are frequently diagnosed when they are already in advanced, palliative stages, with a high degree of disability, and when clinical differentiation between PSP and CBD is particularly challenging due to symptom overlap and variability in presentation. The research led by Dr. Ignacio Illán-Gala proposes an innovative strategy based on the combination of novel imaging markers and plasma biomarkers, with the aim of shifting diagnosis toward minimally symptomatic stages. This shift is critical because it is precisely during these early phases that disease-modifying treatments are expected to be most effective.

The project will assess the performance of this multimodal approach both to increase diagnostic accuracy and to more reliably distinguish PSP from CBD in early stages. It will also examine the longitudinal evolution of these markers and their relationship with clinical progression. This knowledge may improve patient stratification, optimize the design of clinical trials, and ultimately move diagnosis toward a scenario in which care is earlier, more specific, and potentially more disease-modifying.

Epilepsy in Alzheimer’s Disease Associated With Down Syndrome

The third line of research addresses a particularly relevant challenge: the development of epilepsy in individuals with Down syndrome who develop Alzheimer’s disease, a phenomenon that accelerates cognitive decline and increases dependency. In the early stages, these seizures can be difficult to detect because they present in subtle ways.

The research coordinated by Dr. María Carmona-Iragui combines EEG, sleep studies, plasma biomarkers, and magnetic resonance imaging to identify early signs of cerebral hyperexcitability and to understand how this epileptic activity influences disease progression. This integrated approach makes it possible to describe phenomena that often go unnoticed in routine clinical practice.

This analysis is complemented by a phase III clinical trial designed to determine whether levetiracetam can prevent or delay the onset of seizures. This is a pioneering approach that could establish, for the first time, a preventive strategy for this population, with the potential to significantly improve quality of life.

With these three PERIS grants, IR Sant Pau strengthens its leadership in neurodegenerative research and consolidates its commitment to projects that combine scientific rigor, clinical utility, and direct impact on people’s health. Although they address different challenges, these initiatives share a common orientation: translating scientific knowledge into clinical practice to improve early detection, anticipate disease progression, and open new therapeutic opportunities.

Therapy-related myeloid neoplasms represent one of the most significant current challenges in hematologic oncology due to their biological complexity, their aggressive clinical course, and the limited effectiveness of conventional treatments. In this context, biomedical research is seeking new strategies that make it possible to move toward more precise approaches tailored to the characteristics of each patient.

Along these lines, an international research project is being carried out with the participation of the Sant Pau Research Institute (IR Sant Pau), focused on the development of precision medicine strategies to improve the management of this type of hematologic cancer. The study is led by Dr. Manel Esteller, head of the Cancer Epigenetics group at IR Sant Pau, and has received a competitive grant from the Instituto de Salud Carlos III (ISCIII). This is within the framework of the 2025 International Collaboration Projects call of the Strategic Action in Health.

The project will have a total budget of €300,000 and will be carried out over three years (2026–2028), within the context of the European program EP PerMed (European Partnership for Personalised Medicine), which promotes innovative approaches based on pharmacogenomics and the personalization of treatments.

A Molecular Approach to a Highly Complex Hematologic Cancer

Therapy-related myeloid neoplasms arise because of previous oncologic treatments and are characterized by marked molecular heterogeneity, which complicates their clinical management and limits responses to standard therapies. This biological diversity makes it particularly necessary to gain more in-depth insight into the mechanisms underlying the disease and their relationship with treatment response.

In this regard, the project proposes an advanced molecular characterization of the disease with the aim of identifying biological profiles that enable improved patient stratification and optimized therapy selection. “Gaining an in-depth understanding of the molecular alterations that characterize these neoplasms is key to moving toward more effective treatments tailored to each patient, especially in a clinical context as complex as that of therapy-related myeloid neoplasms,” explains Dr. Esteller.

To this end, the study will integrate state-of-the-art genomic and transcriptomic technologies, including single-cell analyses, advanced sequencing, and multi-omics analysis strategies, which will provide a detailed view of the biological processes involved in the disease.

Advanced Analysis and International Collaboration

The work will be carried out in collaboration with other national and international research groups within the framework of the networks promoted by EP PerMed. It will make extensive use of scientific infrastructures specialized in genomics, data analysis, and sequencing platforms. This approach will make it possible to obtain an integrated view of the molecular mechanisms involved in the disease and their impact on therapeutic response.

The funding awarded will be used primarily to cover costs associated with advanced scientific services, such as specialized sequencing, the processing, and analysis of large data volumes, international project coordination, and the dissemination of results at scientific conferences. It also covers open-access publications.

Advancing Research in Precision Medicine

The participation of IR Sant Pau in this project reinforces its commitment to translational research and precision medicine. It also involves international initiatives aimed at improving the diagnosis, prognosis, and treatment of complex oncologic diseases through personalised approaches based on molecular knowledge of the disease.

The Sant Pau Research Institute (IR Sant Pau) has obtained two Sara Borrell contracts in the 2025 call of the Instituto de Salud Carlos III (ISCIII), within the framework of the Strategic Action in Health. These grants, aimed at postdoctoral researchers, are designed to support the continuity and consolidation of scientific careers in the field of biomedical research within the National Health System.

The grants have been awarded to Dr. Víctor de la Peña Arteaga and Dr. Iñigo Rodríguez Baz, who will carry out their research activities at IR Sant Pau. Here they will be able to deepen their scientific specialization and advance their research careers in an accredited healthcare research environment.

In the case of Dr. Víctor de la Peña Arteaga, the contract will make it possible to consolidate his research in the field of mental health, with a neurobiological and translational approach focused on treatment-resistant depression. This is within a line of work coordinated by Dr. Narcís Cardoner. His research activity focuses on studying the brain mechanisms involved in therapeutic response, with particular attention to the factors associated with the lack of response to conventional antidepressant treatments.

In this context, Dr. de la Peña’s research includes the identification and validation of biomarkers of functional neuroimaging linked to the clinical evolution of patients with treatment-resistant depression. Integrating this strategy into a clinical setting helps deepen the biological and functional characterization of the disorder and contributes to a more profound understanding of its underlying mechanisms, an area of significant clinical and social impact.

For his part, Dr. Iñigo Rodríguez Baz will conduct his research in the field of dementia, with a specific focus on Lewy body dementia, within a research line coordinated by Dr. Daniel Alcolea. His research centers on the clinical and biological phenotyping of the disease, including its prodromal phases, with the goal of describing its clinical and evolutionary heterogeneity with greater precision.

His work integrates the analysis of biomarkers in different biological fluids—plasma, serum, and cerebrospinal fluid—with neuroimaging and neurophysiological biomarkers, such as magnetic resonance imaging, nuclear medicine techniques, and polysomnography. This multimodal approach enables progress in early diagnosis, patient stratification, and the prediction of clinical progression in Lewy body dementia, a pathology that is notably complex from a diagnostic standpoint.

In both cases, Institut de Recerca Sant Pau serves as the host institution for the grants, providing the institutional and scientific framework necessary for the development of the research activity. The incorporation of Dr. Víctor de la Peña Arteaga and Dr. Iñigo Rodríguez Baz strengthens IR Sant Pau’s commitment to the recruitment and consolidation of postdoctoral research talent. It also aims to advance research lines aligned with priority areas such as mental health and neurodegenerative diseases.

The awarding of these two Sara Borrell contracts adds to the set of competitive grants obtained by IR Sant Pau in the 2025 call. It reinforces its role as a reference environment for postdoctoral training and the development of high-quality biomedical research. This has the potential to advance scientific knowledge and improve patient care.

The Sant Pau Research Institute (IR Sant Pau) has been awarded three highly competitive grants from the Spanish State Research Agency (AEI), corresponding to two Ramón y Cajal contracts and one Juan de la Cierva contract. This recognition reflects the quality of the research carried out at the center and its ability to attract, foster, and project scientific talent. It also promotes the participation and leadership of women in science, a strategic priority that IR Sant Pau actively advances to move toward more diverse and inclusive research.

The Ramón y Cajal grants are aimed at researchers with an outstanding scientific track record. They make it possible both to recruit new profiles and to advance the careers of those already working at centers of excellence, fostering the development of independent lines of research. For their part, the Juan de la Cierva grants support postdoctoral specialization and strengthen the progression of early-career researchers within groups with strong training capacity.

In this context, IR Sant Pau welcomes Dr. Dora Koller through a Ramón y Cajal grant. Dr. Koller is an interdisciplinary researcher whose profile combines genomics, pharmacogenetics, precision medicine, and computational analysis. Her international career, which includes an extended period at Yale University (United States), has focused on identifying complex genetic relationships between physical conditions—such as endometriosis or chronic pain—and psychiatric disorders. She has an extensive national and international collaboration network and plays a prominent role as a lead analyst in major reference consortia, such as the Women’s Health Initiative and the Chronic Pain Genomics Consortium.

Dr. Koller has led pioneering studies that provide an integrated view of mental and physical health. Her expertise in pharmacogenetics platforms and advanced analytical methods represents a strategic boost for the development of new personalized medicine approaches at IR Sant Pau. Dr. Koller will join the Perinatal and Women’s Medicine Group, led by Dr. Elisa Llurba.

The second Ramón y Cajal grant has been awarded to Dr. Marta Cano Català, who was already conducting her scientific work at IR Sant Pau and who, through this grant, strengthens her career trajectory at the center. Dr. Cano is a recognized expert in neuroimaging applied to affective disorders, with a particular interest in the mechanisms of action of rapid-acting antidepressant treatments, such as electroconvulsive therapy (ECT).

Her research has made it possible to identify structural and functional biomarkers that improve understanding of therapeutic response, opening new avenues toward precision psychiatry. Her participation in international consortia such as GEMRIC and ENIGMA helps position IR Sant Pau as a reference center in the field of clinical neuroimaging. Dr. Cano will join the Mental Health Group, led by Dr. Maria J. Portella.

Meanwhile, the Juan de la Cierva grant has been awarded to Dr. Estela Rosell Mases, a new addition to the research group in Endocrinology, Diabetes, and Nutrition, led by Dr. Dídac Mauricio. This contract allows her to strengthen her scientific profile and contribute to a line of work with a strong translational component. Dr. Rosell’s research will focus on evaluating the role of molecules derived from the gut microbiota in metabolic-associated fatty liver disease in in vitro and in vivo experimental models and in human cohorts.

The awarding of these three grants underscores IR Sant Pau’s commitment to scientific excellence, personalized medicine, mental health, translational research, and the promotion of female talent in science. All the beneficiaries are early-career researchers who help strengthen the presence of women in traditionally underrepresented fields, a priority aspect of the center’s strategy to foster equal opportunities and ensure more competitive and equitable research. Through competitive programs such as those of the AEI, IR Sant Pau continues to reinforce its role within the biomedical ecosystem and to generate impactful knowledge to improve people’s health.