Endometriosis, a chronic inflammatory disease that affects approximately one in ten women of reproductive age—around 190 million worldwide—remains poorly understood from a biological perspective, which has historically hindered both its accurate diagnosis and the development of effective treatments. Now, an international study published in Nature Genetics provides new data to better understand the genetic basis and mechanisms involved in this condition.

The work, which analyzes genetic information from nearly 1.4 million women, including more than 100,000 cases of endometriosis, constitutes the largest study conducted to date on this disease. The research has been carried out by researchers in several institutions: Yale University (United States), Universitat de Barcelona, and the Sant Pau Research Institute (IR Sant Pau), among other centers in Europe and the United States. Its results have identified 80 regions of the genome associated with the risk of developing endometriosis, 37 of which had not been previously described, representing a significant advance in understanding its genetic architecture.

“When we study a disease, we need to understand its biological basis. If we do not know what is happening at the molecular level, it is very difficult to develop effective treatments or improve diagnosis,” explains Dr. Dora Koller, from the Perinatal and Women’s Health research group at IR Sant Pau and lead author of the study, who adds that basic research in endometriosis has arrived later than in other areas, which has limited understanding of the disease for years.

“This research leverages a multidisciplinary collaboration to improve endometriosis care. We are dedicated to translating our findings into actionable solutions for women worldwide,” said Dr. Renato Polimanti, senior author and Associate Professor of Psychiatry at the Yale School of Medicine.

This international study also highlights the participation of experts Bru Cormand, Marina Mitjans, and Selena Aranda, from the University of Barcelona Institute of Biomedicine (IBUB), the Sant Joan de Déu Research Institute (IRSJD), and the Mental Health (CIBERSAM) and Rare Diseases (CIBERER) areas of the CIBER.

An Integrative Approach to Understanding the Disease

Beyond the identification of new genetic regions, one of the main advances of the study is its ability to translate these findings into biological knowledge. The researchers did not limit themselves to identifying statistical associations typical of genome-wide studies but integrated genetic data with multiple layers of functional information to understand how these variants influence the expression of genes and proteins and epigenetic processes. This approach has made it possible to go beyond the simple identification of genetic risk and to connect these associations with real biological processes, providing a more comprehensive and mechanistic view of the pathophysiology of endometriosis.

The results indicate that the disease does not respond to a single mechanism but to the interaction of multiple biological processes acting simultaneously and contributing both to its onset and progression. These include inflammation, altered immune response, tissue remodeling, cell proliferation and differentiation, and the formation of new blood vessels, processes that help explain the diversity of clinical manifestations observed among patients.

“What we see is that there is probably not a single cause, but many possible pathways that can contribute to the disease, and these likely vary between women,” notes Dr. Koller. “This finding reinforces the idea that endometriosis should be understood as a complex and systemic disease in which multiple interrelated biological mechanisms are involved,” she continues.

A Heterogeneous Disease With Poorly Defined Subtypes

This biological complexity is reflected in the wide clinical variability of the disease. Some women have hardly any symptoms, while others experience severe and disabling pain or infertility problems that significantly affect their quality of life. This diversity, both in clinical presentation and progression, highlights that endometriosis does not follow a single pattern.

In clinical practice, current classification is mainly based on surgical criteria or the location of lesions, which is limited, as it does not adequately explain differences in symptoms, progression, or response to treatment. This lack of more precise diagnostic tools also contributes to the fact that diagnosis of the disease is often delayed for an average of 7-10 years, even in women with evident symptoms.

“We need to move toward a more biologically based classification, similar to what has happened in cancer, where we now distinguish different subtypes with different behaviors and treatments,” notes Dr. Koller. She also acknowledges that this diagnostic delay is part of the experience of many women. As a patient with endometriosis, she notes that “in my case, it took 15 years to obtain a diagnosis, despite having clear and debilitating symptoms.”

This shift in approach would not only improve understanding of the disease but also allow diagnosis and treatment to be adapted to the specific characteristics of each patient, a key step toward more personalized medicine.

The Combined Role of Genetics and Environmental Factors

The study provides new insights into the role of genetics in endometriosis, although it confirms that genetic predisposition alone does not explain the development of the disease. Genetics only partly explain the development and progression of endometriosis, reinforcing the idea that the disease follows a complex model involving multiple factors.

In this regard, the results suggest that the interaction between genetics, environmental factors, and epigenetic mechanisms is not deterministic. Elements such as diet, exposure to certain chemical compounds, and many other factors may modulate its development and progression.

This approach helps explain why women with a similar genetic predisposition may present very different clinical trajectories, both in the onset of symptoms and in their severity or response to treatment. The observed variability does not depend solely on genetic load but on how it interacts with the environment over time.
Moreover, the analysis of polygenic risk combined with clinical information provides a particularly relevant result: in some cases, symptoms and comorbidities may play a more decisive role than genetics itself in identifying the disease. This finding challenges the idea that genetic risk is always the main indicator and reinforces the importance of a comprehensive clinical evaluation.

“In clinical practice, symptoms remain a key piece,” notes Dr. Koller. “Listening to patients and understanding their clinical history is essential when guiding diagnosis.” This perspective reinforces the need to more closely integrate genetic and clinical information in healthcare practice, with the aim of improving patient identification and advancing toward more precise and personalized care models.

New Opportunities for Diagnosis and Personalized Treatment

The study findings have direct implications in the clinical setting. Currently, the treatment of endometriosis is largely based on a trial-and-error approach, in which many patients try different therapies without obtaining satisfactory results, reflecting the lack of tools to predict individual response to treatments.

“The problem is not only that treatments do not work the same in all patients but that we do not have enough tools to anticipate which option will be most appropriate in each case,” explains Dr. Koller. “Genetics can help us better understand what is happening in each patient and guide therapeutic decisions more closely aligned with their biological profile.”

In this way, the integration of genetic, clinical, and molecular information opens the door to a more personalized approach, in which treatment can be adapted to the specific characteristics of each patient. This shift would improve the effectiveness of therapies and reduce unnecessary exposure to ineffective treatments.

The study also identifies potential new therapeutic options through the repurposing of existing drugs, a strategy that allows accelerating the application of new treatments for endometriosis by building on medications with already known safety profiles. These include drugs used in oncology and others such as nortriptyline, which could have a dual effect by acting on both chronic pain and depression, two conditions frequently associated with the disease.

Clinical Impact, Diagnostic Challenges, and the Need for a Gender Perspective

Beyond its scientific contribution, this research is rooted in an urgent clinical and social reality: endometriosis remains a widely underdiagnosed disease that is too often normalized or dismissed. Diagnosis is frequently delayed by several years, a delay that not only limits access to appropriate treatment but also allows pain to become chronic and complications such as fertility problems or emotional distress to develop, among many others. It is precisely this reality that makes advancing our biological understanding of the disease so critical.

“Severe pain is never normal. If a woman cannot get out of bed during menstruation, it is a sign that something is wrong, and we must investigate it,” emphasizes Dr. Koller. Beyond the specific case of endometriosis, these results point to a broader challenge in biomedical research. “Diseases that exclusively affect women have historically been under-researched and have received fewer resources,” notes Dr. Koller. “Incorporating a gender perspective in research is not only a matter of equity but a necessity to advance knowledge and improve care.”

Reference Article:

Koller D, He J, Løkhammer S, Aranda S, Qiu D, Davtian D, Chen Q, Xu Z, Mao Z, Friligkou E, Karaca S, Cormand B, Flores I, Altmäe S, Mitjans M, Cabrera-Mendoza B, Polimanti R. Multi-ancestry genome-wide association and integrated multi-omics analyses of endometriosis and its clinical manifestations. Nature Genetics. 2026. https://doi.org/10.1038/s41588-026-02582-2

The vascular imbalance that occurs in some pregnancies may leave a lasting imprint beyond childbirth. A study led by the Sant Pau Research Institute (IR Sant Pau), published in the American Journal of Obstetrics and Gynecology, shows that this alteration, reflected by the sFlt-1/PlGF ratio, is associated with a higher risk of memory problems between three and six years after pregnancy and provides new insights into the vascular mechanism that may underlie this effect.

Recently, several studies have linked preeclampsia to a higher risk of cognitive impairment, including memory alterations and even structural brain changes decades after pregnancy. However, the available evidence has mainly focused on the very short term—where factors such as sleep deprivation or postpartum stress play a role—or on the long term, with intervals of up to 30 or 40 years, making it difficult to establish a direct relationship. In this context, this study is the first to specifically analyze the medium-term impact after pregnancy.

“Analyzing this intermediate period makes it possible to reduce the influence of postpartum-related factors and to more clearly observe the impact of the underlying vascular process, at a time when patients have already regained a certain level of stability,” explains Dr. Pablo García-Manau, researcher in the Perinatal and Women’s Health group at IR Sant Pau and one of the study’s authors.

Higher Risk of Memory Alterations

The study included 266 women evaluated after pregnancy, in whom angiogenic status during gestation had been measured using the sFlt-1/PlGF ratio, which is used in clinical practice. Angiogenic imbalance was considered to be present when this ratio was equal to or greater than 38. Of the total cohort, 30% had experienced preeclampsia, allowing comparison of the evolution of different profiles under real clinical conditions. Memory function was analyzed using the validated MFE-30 questionnaire, a widely used tool that assesses memory failures in daily life based on patients’ self-perception, including aspects such as frequent forgetfulness or difficulty retaining recent information.

The results indicated that women with angiogenic imbalance had a higher frequency of memory alterations (30.0% vs. 16.2%) and approximately twice the likelihood of experiencing memory difficulties, even after accounting for other clinical factors. This finding remained after considering variables such as body mass index, educational level, and hypertension.

In the case of preeclampsia, women who had experienced it initially showed more memory problems, but this difference was no longer significant after accounting for these same factors. In contrast, angiogenic imbalance remained associated with these difficulties, suggesting that the key factor is not preeclampsia itself, but rather the accompanying vascular alteration.

“We are not saying that preeclampsia is not associated with cognitive impairment, but rather that we are beginning to identify the mechanism that may explain it,” notes Dr. García-Manau. “This angiogenic imbalance can appear even in women without clinical preeclampsia, which broadens the group of patients who may be at risk.”

Beyond Preeclampsia

The sFlt-1/PlGF ratio is a marker used in clinical practice to assess the risk of preeclampsia, as it reflects an imbalance in the factors that regulate blood vessel function during pregnancy. When this ratio is altered, it indicates a state of endothelial dysfunction and poorer vascular adaptation, associated not only with obstetric complications but also with increased vulnerability in different organs.

From a biological perspective, this angiogenic alteration could trigger persistent changes in the microcirculation. This phenomenon, previously described in the cardiovascular and renal systems, could also affect the brain, compromising perfusion in particularly sensitive regions such as the hippocampus, which is key in memory processes.

“These results suggest that vascular imbalance during pregnancy may reflect a broader process that also impacts the brain and may explain the memory alterations observed years later,” explains Dr. García-Manau.

What These Results Mean

Although the findings open a new line of research, the authors emphasize that it is still too early to translate these results into clinical practice. “This study defines a possible pathophysiological mechanism, but we need to confirm it with objective memory tests and neuroimaging techniques,” says Dr. García-Manau.

In this regard, the next step will be to determine whether these subjective alterations—based on patients’ own perceptions—correspond to measurable changes at the cognitive and brain levels, as well as to validate these results in larger cohorts that will allow more precise identification of which subgroups of women are at higher risk.

Beyond its immediate application, the study introduces a relevant shift in how these complications are interpreted: it suggests that angiogenic markers could be used in the future not only to assess obstetric risk but also to anticipate potential medium- and long-term consequences for women’s health.

“This type of marker could help us identify which women have greater vulnerability and require closer follow-up, but also to better understand how certain processes that begin during pregnancy can have an impact on health in the medium and long term,” the researcher concludes.

Reference Article:

Platero J, Garcia-Manau P, Costa N, Garcia Z, Garrido-Giménez C, Pellicer C, Ullmo J, Jordi M, Nan M, Mora J, Garcia-Osuna A, Sánchez-Garcia O, Choliz M, Cruz-Lemini M, Llurba E. Abnormal soluble fms-like tyrosine kinase to placental growth factor ratio during pregnancy and subjective memory impairment 3 to 6 years postpartum. American Journal of Obstetrics and Gynecology. 2026. https://doi.org/10.1016/j.ajog.2026.02.028

A study led by the Sant Pau Research Institute (IR Sant Pau) and the CIBER of Cardiovascular Diseases (CIBERCV) has identified a new protective mechanism involved in the development of abdominal aortic aneurysm (AAA), a serious cardiovascular disease for which there are currently no effective pharmacological treatments to halt its progression. The findings, resulting from collaboration between several CIBERCV groups and the Obesity and Nutrition area (CIBEROBN), have been published in British Journal of Pharmacology.

Extracellular matrix remodeling is a key process in abdominal aortic aneurysm (AAA); however, the key matrix components that regulate vascular integrity and remodeling processes remain poorly understood. In this context, the research team identified the extracellular matrix protein thrombospondin-4 (TSP4) as a key factor in the development of the disease.

“Abdominal aortic aneurysm is a silent and potentially lethal disease for which only surgical treatment is currently available in advanced stages. Identifying factors such as TSP4, which help limit vascular damage, is essential to move toward effective pharmacological therapies,” says Dr. Cristina Rodríguez, researcher at IR Sant Pau and CIBERCV and coordinator of the study.

“In a large cohort of patients and donors, as well as in mouse models, we have demonstrated that TSP4 is activated early and persistently during aneurysm development,” explains Dr. José Martínez González, group leader at CIBERCV at the Institute for Biomedical Research of Barcelona-CSIC and co–principal investigator of the study together with Dr. Rodríguez Sinovas.

“We confirmed a significant increase in THBS4 gene mRNA levels and TSP4 protein in the aorta in AAA, and observed that THBS4 is overexpressed early in pre-aneurysmal lesions,” notes Dr. Rodríguez. In addition, the team observed that inhibition of this protein accelerates disease progression, increasing inflammation and vascular damage.

The team states that thrombospondin-4 is not simply a marker of the pathological process, but rather plays an active and protective role in maintaining vascular wall stability. The coordinators conclude that the findings reveal the protective role of TSP4 and suggest that its modulation could represent a new therapeutic strategy to improve vascular wall stability in AAA.

Article Reference:

Thrombospondin-4 is upregulated in abdominal aortic aneurysm: A vasoprotective response with potential therapeutic relevance. Laia Blanco-Casoliva, Lidia Puertas-Umbert, Judith Alonso, Rafael Almendra-Pegueros, Saray Varona, Mercedes Camacho, Gemma Arderiu, Lluís Asmarats, Marta Alegret, Jose Martínez-González, Cristina Rodríguez. https://doi.org/10.1111/bph.70402

Despite advances in biomedical research, women’s health remains underrepresented in many areas of innovation and clinical practice, with gaps in diagnosis, treatment, and knowledge generation. To address this challenge, the XWHIN (Women’s Health Innovation Network) was created, led by the Institut de Recerca Sant Pau (IR Sant Pau). On April 24, it held its first public working session at the Sant Pau Art Nouveau Site as part of the scientific meeting “Entre Dones,” with the participation of more than 80 professionals. This participatory event on women’s health, organized by Hospital de Sant Pau, provided a space to discuss, share, and learn about women’s health from a gender perspective.

The meeting was opened by Lourdes Puigbarraca, Deputy Director General for Transfer and Society of the Government of Catalonia, and included a presentation of the network by Dr. Maria Rosa Ballester, Head of Responsible Research and Innovation at IR Sant Pau and Director of XWHIN. The session was structured around short talks by experts from different fields, discussion spaces, and co-creation dynamics, with the aim of fostering interdisciplinary dialogue and identifying opportunities to advance the integration of sex and gender perspectives in health research and innovation.

The meeting also served to present the network’s visual identity and to outline its strategic objectives, aimed at promoting a new way of conducting research and innovation in women’s health. As Dr. Ballester highlights, “the creation of XWHIN responds to the need to systematically incorporate sex and gender perspectives into health research and innovation,” and this first gathering “has been the first step in activating a network that seeks to generate useful knowledge and drive innovation projects with real impact on women’s health and on the population in all its diversity.”

XWHIN positions itself as a pioneering initiative that systematically integrates this perspective across all phases of R&D&I, with the goal of generating more equitable solutions with real impact on clinical practice and society. The network is funded by the Agency for Management of University and Research Grants (AGAUR) of the Department of Research and Universities of the Government of Catalonia.

Experts Across Different Fields Identify Key Challenges for Innovation in Women’s Health

During the first part of the meeting, seven specialists from different fields—oncohematology, neurovascular health, mental health, cardiovascular health, epidemiology and public health, primary care, and reproductive health—shared, in five-minute presentations, the key challenges in their areas to advance innovation in women’s health by integrating sex and gender perspectives into research and clinical practice.

The presentations provided a broad and complementary overview of current challenges. Across the board, they highlighted the need for more representative data and for the integration of sex and gender perspectives from the earliest stages of research through to their translation into clinical practice. It was also emphasized that the absence of this perspective generates scientific bias and has direct consequences for diagnosis, treatment, and equity in healthcare. In this regard, the talks underscored the importance of promoting interdisciplinary approaches capable of integrating the complexity of biological, clinical, and social factors that influence health, moving toward more precise, inclusive solutions adapted to population diversity.

Overall, the presentations showed that progress in this direction requires a shared vision and greater coordination among the different stakeholders in the ecosystem, including research, clinical practice, innovation, and society, laying the groundwork for collaborative workspaces aimed at identifying opportunities and activating new lines of action.

Co-Creation to Transform Research in Women’s Health

The meeting continued with a collaborative working session in which participants organized into groups to identify needs, opportunities, and potential lines of action, using a participatory methodology.

Among the main areas of reflection, participants highlighted the need to make data more visible and accessible, as well as to promote its generation based on criteria that incorporate sex and gender perspectives. They also pointed to the importance of advancing shared standards for data collection and use and of developing mechanisms to facilitate its application in research and clinical practice.

In addition, the need to align funding mechanisms with this perspective and to strengthen coordination across different levels of the system—from public policy and institutions to clinical practice and research—was emphasized. The discussion also highlighted the value of promoting cultural and organizational changes that support its integration, including the development of role models, citizen participation, and increased awareness among professionals.

The conclusions drawn by the groups formed a first map of shared priorities that will guide XWHIN’s strategic plan in the coming months, with the aim of promoting coordinated actions with real impact on the system.

XWHIN: A Commitment to More Equitable Innovation

This meeting marks the starting point of XWHIN’s public activity, a pioneering network in Catalonia designed to connect the different stakeholders in the ecosystem—research, clinical practice, innovation, industry, and patients—and to create a stable collaborative space aimed at transforming the way women’s health is addressed. This first gathering made it possible to share knowledge, identify common challenges, and begin defining joint lines of work to address identified needs.

With this approach, XWHIN promotes a model that systematically integrates sex and gender perspectives across all phases of R&D&I, from knowledge generation to its application in clinical practice. The network is created with the aim of reducing existing health inequalities and promoting more precise, inclusive innovation aligned with the specific needs of the population, fostering collaborative projects with the capacity to generate real impact on the healthcare system.

Despite advances lately, sepsis remains one of the leading causes of mortality worldwide, and its management faces significant clinical and scientific limitations. In this context, The Lancet has launched a new international commission that is now beginning its work and includes the participation of Dr. Otavio Ranzani, researcher at the Institut de Recerca Sant Pau (IR Sant Pau) and head of the SalutData Lab—Data and Health Laboratory.

Sepsis is a severe clinical syndrome that occurs when the body’s response to an infection becomes dysregulated, leading to organ dysfunction. This syndrome continues to represent a major global health problem, both because of its high mortality and the challenges associated with its diagnosis and treatment across different healthcare settings.

“Sepsis requires a shift in approach that goes beyond traditional models and allows for better integration of biological research, clinical practice, and healthcare system organization,” says Dr. Otavio Ranzani. “Only with a more global and coordinated perspective will it be possible to advance in its prevention, diagnosis, and treatment.”

The commission has been publicly introduced with the publication in The Lancet of its first article, a programmatic paper that marks the beginning of its work and establishes the foundations for developing an international agenda in the coming years. This initial document identifies the main outstanding challenges in the global management of sepsis and defines the commission’s priority areas of work.

Outstanding Challenges in Sepsis Management

One of the main challenges identified is the lack of consensus on definitions and surveillance criteria at the global level, resulting in highly variable estimates of incidence. This situation highlights the need to establish standardized definitions that enable better measurement of the burden of this syndrome and facilitate comparisons across studies.

In addition, the absence of globally validated diagnostic tools remains a major limitation. In practice, this implies reliance on microbiological testing ranging from culture-based methods to pathogen sequencing techniques, along with inflammatory biomarkers such as procalcitonin, C-reactive protein, or cytokines. These tools show context-dependent diagnostic performance, uneven availability across countries, and, often, limitations related to cost and access to diagnostic services, making accurate identification and reliable epidemiological estimates difficult.

“The challenge is not only to improve the available tools but to rethink how we understand sepsis as a complex clinical process,” says Dr. Otavio Ranzani. “Without this shift in perspective, it will be difficult to move toward more precise models that allow diagnosis and treatment to be tailored to each patient.”

Furthermore, although biological and clinical heterogeneity is recognized, scientific advances remain limited. Despite the development of innovative clinical trials, there is still a lack of evidence for effective immunomodulatory therapies that improve survival. This is partly because studies continue to focus on individual mediators, whereas clinical outcomes depend on multiple interrelated biological mechanisms that, in numerous instances, are not yet fully understood.

An International Initiative to Define New Strategies

In this context, the commission led by The Lancet aims to carry out a systematic evaluation of epidemiology and of the clinical, biological, and health system factors that shape its management. It aims to identify the main current limitations and propose solutions on a global scale.

The initiative recommends the development of a comprehensive framework covering the entire continuum, from infection prevention and early detection across all levels of care to patient treatment and follow-up, adapted to differences between healthcare systems. It also explicitly incorporates the long-term impact, an area that remains underexplored despite its clinical relevance, and addresses the interaction between sepsis, patients’ prior health status, and socioeconomic factors, which influence both risk and outcomes.

“This work seeks to lay the groundwork for better evidence-based decision-making, both in clinical practice and public health,” adds Dr. Otavio Ranzani. “Advancing in this field requires integrating clinical, biological, and health system data.”

The commission will carry out its work over the coming years with the goal of generating recommendations and publications that help guide the management of this syndrome at the international level. In this framework, the participation of IR Sant Pau places the institution within a leading international initiative at a key moment in defining its lines of work, with Dr. Otavio Ranzani contributing to the analysis of epidemiology and the identification of major challenges in its management.

Reference Article:

Shankar-Hari M, Ming D, Mendelson M, Rupali P, Adhikari NKJ, Ranzani O, Randolph A, Davenport E, van der Poll T, Moita LF, Beane A, Lamontagne F, Kwizera A, Holmes A, Diaz J. The Lancet Commission on Sepsis: transforming sepsis care and outcomes. Lancet 2026. https://doi.org/10.1016/s0140-6736(26)00648-3

A multicenter study with participation from the Institut de Recerca Sant Pau (IR Sant Pau) has delved deeper into the genetic mechanisms of encephalopathy associated with the SYNGAP1 gene. This rare disease is characterized by epilepsy, intellectual disability, psychomotor delay, and, in numerous instances, autism. The study, published in Neurobiology of Disease, shows that disease severity does not depend solely on the primary mutation but also on other genetic factors that may modulate its clinical expression.

The research, led by teams from the University of Barcelona, the Sant Joan de Déu Research Institute, and CIBER, also includes participation from IR Sant Pau, with Dr. Àlex Bayés, head of the Molecular Physiology of the Synapse group at this center, as corresponding author of the study.

“This work shows that, even in diseases considered monogenic, the biological reality is more complex than previously thought,” says Dr. Bayés. “Clinical variability among patients cannot be explained solely by the mutation in SYNGAP1, but rather by the presence of other genetic factors that significantly influence disease progression.”

A Genetic Disease with Highly Diverse Manifestations

SYNGAP1 encephalopathy is caused by alterations in a key gene for brain development and cognitive function. Despite this well-defined origin, its clinical manifestations are highly heterogeneous, which complicates both prognosis and clinical management of patients.

In this context, the study analyzed a cohort of 44 patients from 16 hospitals across Spain, all carrying dominant mutations in SYNGAP1. A detailed genotype–phenotype analysis confirmed that patients with alterations in the same gene can present very different clinical profiles. “We are not dealing with a simple cause-and-effect relationship,” notes Dr. Bayés. “These results require a more nuanced interpretation of genetic information, considering the complexity of the genome as a whole.”

New Variants and the Role of Genetic Context

The study identified four new variants of the SYNGAP1 gene that had not been previously described, expanding knowledge of the genetic basis of this encephalopathy. Beyond this finding, massive sequencing analysis also revealed alterations in other genes that interact with the SYNGAP1 protein, such as SHANK1, SHANK3, or NLGN2, pointing to the existence of modifier genes capable of influencing the clinical expression of the disease.

In this regard, the results reinforce the idea that the patient’s overall genetic context plays a relevant role in the observed variability. “Identifying variants in genes that are part of the same synaptic network suggests that the patient’s global genetic context plays a determining role,” explains Dr. Bayés. “This allows progress toward a more integrated understanding of these disorders.”

Factors Influencing Disease Severity

Another aspect addressed in the study was the potential relationship between mutation characteristics and the severity of the clinical picture. The results indicated that the location of the variant within the gene may be a relevant factor and that certain regions are associated with distinct clinical manifestations.

In particular, variants located in the PH domain were associated with milder forms of the disease, with less language impairment, lower frequency of epilepsy, and overall lower severity. However, this relationship is partial and does not allow for conclusive prediction of individual patient outcomes, reinforcing the complexity of the genotype–phenotype relationship.

“It is not enough to identify the mutation; it is necessary to understand its location and the genetic context in which it appears,” says Dr. Bayés. “This approach is key to advancing toward more personalized medicine.”

Implications for Diagnosis and Research

The study’s findings have relevant implications for the clinical management of this encephalopathy, as identifying genetic patterns associated with different levels of severity could help anticipate disease progression and better guide therapeutic decision-making. At the same time, the work reinforces the classification of SYNGAP1 encephalopathy as one of the monogenic forms of autism spectrum disorder, present in approximately two-thirds of patients.

Overall, these findings contribute to redefining the understanding of rare genetic diseases and open new lines of research aimed at identifying biomarkers and potential therapeutic targets. “Advancing knowledge of the factors that modulate these diseases is essential to improve their diagnosis and, in the future, their treatment,” concludes Dr. Bayés.

Reference Article:

Aranda S, Ribeiro-Constante J, Tristán-Noguero A, Moreno-Ruiz N, Arenas C, Calvo FFM, Ibañez-Mico S, Segura JLP, Ramos-Fernández JM, Del Carmen Moyano Chicano M, León RC, Soto-Insuga V, González-Alguacil E, Dávila CV, Fernández-Jaén A, Plans L, Camacho A, Visa-Reñé N, Del Pilar Martin-Tamayo Blázquez M, Paredes-Carmona F, Marti-Carrera I, Ginot-Julià G, Hernández-Fabián A, Davi MT, Sanchez MC, Herraiz LC, Pita PF, Gonzalez TB, O’Callaghan M, Iglesias Santa Polonia FF, Cazorla MR, Lucas MTF, González-Meneses A, Sala-Coromina J, Macaya A, Lasa-Aranzasti A, Anna M, Cueto-González, Párraga FV, Plana JC, Serrano M, Alonso X, Palafoll MIV, Monteagudo E, Alonso-Colmenero I, Capdevila OS, Casals F, Cormand B, García-Cazorla A, Bayés À, Mitjans M. Genotype-Phenotype Correlations and Putative Modifier Genes in SYNGAP1 Encephalopathy. Neurobiology of Disease. 2026 Mar 17;107357. https://doi.org/10.1016/j.nbd.2026.107357

Dr. Sònia Sirisi Dolcet, a researcher in the Neurobiology of Dementia group at the Institut de Recerca Sant Pau (IR Sant Pau), has been awarded a grant from the José Castillejo international mobility program, promoted by the Ministry of Science, Innovation, and Universities. This program funds research stays at leading international institutions with the aim of strengthening researchers’ training and international projection.

The grant allows the researcher to carry out her project at the University of Pennsylvania in the United States, one of the leading international centers in the study of neurodegenerative diseases. The three-month stay will take place at the Perelman School of Medicine, in the laboratory led by Dr. David Irwin, a specialist in neuropathology.

During this period, Dr. Sirisi will work on the characterization of new monoclonal antibodies targeting a fragment of the amyloid precursor protein (APP), an emerging target in Alzheimer’s research. “This grant represents a key opportunity to advance a line of research that we are developing at IR Sant Pau and that may help better understand mechanisms that have so far been underexplored in Alzheimer’s disease,” explains the researcher.

Alzheimer’s disease is characterized by the accumulation of proteins such as amyloid-β and tau, considered the main neuropathological markers. However, recently, evidence has emerged pointing to the involvement of other mechanisms in neuronal dysfunction. In this context, the project focuses on the study of APP-derived fragments that may play a relevant role in the development of the disease.

The work will be based on the analysis of these antibodies in human brain tissue postmortem from different neurodegenerative conditions, including sporadic and genetic Alzheimer’s disease, as well as other tauopathies. The aim is to identify specific patterns of accumulation of these fragments and to study their relationship with key disease processes, such as amyloid deposition, tau pathology, and neuroinflammation. “Studying these antibodies in new cohorts will allow us to validate whether the pattern observed so far is reproduced across different neuropathological contexts and to advance our understanding of their role in disease progression,” adds Dr. Sònia Sirisi.

This approach will make it possible to assess the potential of these antibodies both as research tools and as possible therapeutic targets. All of this comes in a context where, despite recent advances in amyloid-targeting treatments, there remains a need to develop more effective strategies to modify the course of the disease.

The collaboration between IR Sant Pau and the University of Pennsylvania team is part of a well-established line of work between both groups, which have already collaborated on several studies in the field of Alzheimer’s disease and frontotemporal dementia. This new stay strengthens this international cooperation and opens the door to future joint research lines in the field of neurodegenerative diseases.

Parkinson’s disease is the second most common neurodegenerative disorder and affects more than 160,000 people in Spain, with an estimated prevalence of between 20,000 and 25,000 patients in Catalonia. In the context of World Parkinson’s Day, Hospital de Sant Pau hosted a meeting organized by the Catalan Parkinson’s Association in which specialists analyzed the advances that are transforming the diagnosis, treatment, and research of this condition.

The event brought together more than 220 participants, including patients, caregivers, and healthcare professionals, with a program that combined education, reflection, and participation. The meeting began with a lecture focused on how Parkinson’s disease can manifest differently depending on factors such as age or sex, delivered by Dr. Núria Caballol, neurologist at Hospital Universitari de Bellvitge. This was followed by a session dedicated to advances in research and treatment, in a dialogue format between experts moderated by Dr. Jaime Kulisevsky. He is head of the Parkinson’s Disease and Movement Disorders research group at the Institut de Recerca Sant Pau (IR Sant Pau). The session concluded with an open Q&A segment in which attendees were able to address their questions directly to the professionals.

A New Way of Understanding the Disease

Although it has traditionally been associated with motor symptoms such as tremor or rigidity, it is now known that Parkinson’s disease also involves a wide range of non-motor symptoms—such as sleep disturbances, depression, or cognitive impairment. These can be even more disabling and play a decisive role in disease progression. During the meeting, specialists agreed that one of the most significant changes recently has been a transformation in the way Parkinson’s disease is understood, both from a clinical and biological perspective.

“We are seeing the disease in a very different way. Today we know that Parkinson’s disease has a very long trajectory and can begin many years before the first symptoms appear. This shift in perspective opens a window of opportunity to intervene earlier and move toward treatments that can modify its progression,” explained Dr. Maria Josep Martí, neurologist at the Parkinson’s Disease and Movement Disorders Unit at Hospital Clínic de Barcelona.

Dr. Eduard Tolosa, neurologist and expert in Parkinson’s disease, emphasized the growing relevance of non-motor symptoms, which have traditionally been underrecognized in clinical practice. “For many years we focused on motor symptoms, but today we know that problems such as depression, sleep disorders, or autonomic dysfunction are very common and have a major impact on quality of life, and therefore require specific attention and a more comprehensive approach,” he noted.

Advances in Diagnosis: Toward Biomarkers

The diagnosis of Parkinson’s disease has also undergone significant advances lately. As Dr. Tolosa explained, there has been a shift from an approach based almost exclusively on clinical criteria—grounded in the observation of symptoms—to the progressive incorporation of biomarkers that allow the disease to be objectively measured. “We are beginning to have tools that can detect alpha-synuclein aggregates in cerebrospinal fluid or even in the skin, which provides greater diagnostic certainty and may be key to better selecting patients for clinical trials,” he highlighted.

These advances represent an important change, as they make it possible to reduce diagnostic uncertainty, especially in early stages or in cases with atypical presentations. In addition, they facilitate the identification of patients at earlier stages, when therapeutic interventions may have a greater impact. In this context, biomarkers are emerging as a key tool not only to improve diagnosis, but also to drive the development of new therapies by enabling better patient stratification and more precise evaluation of treatment responses in research settings.

New Therapeutic Strategies and Improved Clinical Management

In the therapeutic field, experts highlighted the evolution seen in recent decades, particularly in the treatment of more advanced symptoms. “Recently, one of the most significant advances has been the development of new ways to administer levodopa continuously, especially via the subcutaneous route, which helps improve the control of fluctuations in patients with advanced disease,” explained Dr. Tolosa.

These advances reflect a progressive shift toward more sophisticated treatments tailored to the evolution of each patient. The ability to maintain more stable medication levels helps reduce motor fluctuations and improve autonomy in advanced stages of the disease. Antonia Campolongo, specialist nurse at Hospital Sant Pau, assessed the impact of these changes in daily clinical practice. “We have moved from primarily oral treatments to much more complex and personalized therapies, such as infusions or continuous delivery systems, which require close monitoring but allow better disease control,” she stated.

A Diversifying Research Landscape: Genetics, Inflammation, and New Targets

Research in Parkinson’s disease is increasingly focused on developing therapies capable of modifying the course of the disease, although this remains a complex goal. “For years we have focused many efforts on alpha-synuclein, but the results of clinical trials have not met expectations, which forces us to broaden our scope and explore other pathways,” noted Dr. Tolosa. As a result, research lines are diversifying toward new biological targets. “Different molecular pathways are being studied, including genetic factors and inflammatory processes, which may be involved in the disease and open new therapeutic opportunities,” explained Dr. Martí.

This strategic shift responds to the need to better understand the heterogeneity of Parkinson’s disease and to develop more specific approaches. The study of genetically based cases—although they represent a small proportion—allows progress toward more targeted treatments and may provide insights applicable to the disease as a whole. Overall, this diversification reflects a transitional phase in research, in which expanding hypotheses and developing new approaches could be decisive in achieving significant advances in the coming years.

The Key Role of Clinical Trials

Specialists also emphasized the importance of patient participation in clinical trials as a fundamental component of scientific progress. “Participating in a clinical trial does not mean being a ‘guinea pig.’ It is an opportunity to access new therapeutic options and to contribute directly to the advancement of knowledge,” Campolongo stated.

In addition to facilitating the development of new therapies, these studies enable closer and more structured patient follow-up, which can translate into better care and a more profound understanding of disease progression. Encouraging participation in clinical trials is therefore a key element in accelerating research and translating scientific advances into clinical practice.

Looking Ahead: A Cautiously Optimistic Perspective

Although there are still no treatments capable of slowing or curing the disease, specialists agreed on conveying a message of cautious optimism. “We have made great progress in symptom control and in understanding the disease, and it is very likely that the coming years will bring significant advances, especially if we can intervene at earlier stages,” noted Dr. Jaime Kulisevsky.

Among emerging lines of research, Dr. Tolosa highlighted the potential of cell-based therapies. “Strategies based on the implantation of cells capable of producing dopamine are being developed and could represent a new therapeutic avenue in the future if their results are confirmed,” he pointed out.

Parkinson’s disease remains a major biomedical challenge, but also a rapidly evolving field in which advances in research are opening new pathways to improve diagnosis, treatment, and the quality of life of affected individuals.

Despite advances in cardiology, women continue to face significant disparities in the prevention, diagnosis, and treatment of ischemic heart disease—a condition caused by reduced blood flow to cardiac tissue and the leading cause of cardiovascular death worldwide. A study published in the European Heart Journal as a scientific position paper from the “Working Group on Coronary Pathophysiology and Microcirculation” and associations (ACVC and EAPCI) of the European Society of Cardiology (ESC) highlights how sex and gender differences play a decisive role in cardiovascular risk, pathophysiology, and prognosis in ischemic heart disease. It underscores the need to systematically integrate this perspective into clinical practice and research.

Far from being a simple variation of the male model, ischemic heart disease in women shows distinct characteristics across the entire disease continuum, from risk factors to clinical outcomes. “For decades, coronary artery disease has been studied and treated from a predominantly androcentric perspective, contributing to the underdiagnosis and suboptimal treatment of many women,” explains Dr. Teresa Padró, head of the Cardiovascular Disease Biomarkers Research Group at the Institut de Recerca Sant Pau (IR Sant Pau) and researcher at the Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), and corresponding author of the study.

Risk and Pathophysiology: A Different Ischemic Heart Disease in Women

In women, classic cardiovascular risk factors such as smoking, diabetes mellitus, and hypertension have a greater relative impact than in men. This profile is further shaped by female-specific risk factors, including pregnancy-related complications (preeclampsia, gestational hypertension, preterm delivery, or fetal growth restriction) and early menopause, all associated with an increased later risk of ischemic heart disease. A potentially unfavorable effect of hormone replacement therapy is also noted when initiated in older women or many years after menopause onset.

From an anatomical and functional perspective, women’s coronary circulation has relevant particularities, such as smaller vessel caliber and a more diffuse pattern of atherosclerotic disease. In addition, women more frequently present with non-obstructive coronary artery disease, microvascular dysfunction, and coronary spasm, all of which can cause myocardial ischemia even in the absence of significant stenosis. “Understanding this pathophysiology is key to explaining why many women present clear symptoms of ischemia without evident obstructive lesions on conventional angiography,” notes Dr. Padró.

When Diagnosis and Treatment Do Not Reflect Women’s Reality

The way ischemic heart disease manifests in women directly contributes to healthcare disparities. Compared with the typical chest pain seen in men, women more often present less specific symptoms, such as dyspnea, fatigue, or general discomfort, which lowers initial clinical suspicion and delays diagnosis. This issue is compounded by a historical bias in symptom interpretation, based on predominantly male patterns.

Differences also extend to the diagnostic setting. Women tend to have lower coronary flow reserve, while fractional flow reserve may be higher for the same degree of stenosis, reflecting the contribution of microvascular dysfunction to ischemia. Moreover, some traditional diagnostic tests perform less effectively in women, whereas functional imaging techniques and microcirculation-specific tests help detect ischemia in the absence of obstructive disease. When these factors are not considered, there is a real risk of underdiagnosis. “If these differences are not correctly interpreted, ischemic heart disease in women may go unnoticed or be inadequately treated,” Dr. Padró warns.

Regarding treatment, significant inequalities persist. Women are less likely to receive evidence-based therapies and invasive procedures, and they show higher rates of treatment discontinuation, partly due to adverse effects. These differences, combined with distinct risk profiles and clinical characteristics, result in worse clinical outcomes, especially after acute coronary syndrome, with higher mortality in women—particularly at younger ages—even after adjusting for baseline characteristics, treatments, and time to care.

Scientific Evidence and the Need for a Paradigm Shift

One of the main limitations identified is the underrepresentation of women in randomized clinical trials, which affects the robustness of available evidence. Many studies are not designed to analyze sex and gender differences, making it difficult to identify variations in treatment efficacy, safety, or adverse effects in women and limiting the applicability of findings to clinical practice.

This lack of specific evidence perpetuates disparities in the management of ischemic heart disease and hinders progress toward a more personalized approach to medicine. To address this, it is essential to increase women’s participation in clinical trials and to design studies that explicitly incorporate a sex- and gender-based perspective from the outset.

The study also emphasizes the need to enhance awareness and training among healthcare professionals, optimize diagnostic strategies, and promote organizational and health policy changes to ensure more equitable cardiovascular care. “Systematically integrating a sex- and gender-based perspective into research and clinical practice is essential to improving women’s cardiovascular health,” Dr. Padró concludes.

This approach aligns with the research conducted at IR Sant Pau, where cardiology research prioritizes the pathophysiological mechanisms of cardiovascular disease and their clinical application, with increasing attention to sex and gender differences. The participation of IR Sant Pau researchers in internationally recognized work such as this reinforces the institution’s commitment to rigorous, translational cardiovascular research aimed at improving health outcomes.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition, but to date, approaches have focused primarily on childhood. As a result, many adults lack the tools to face key challenges such as employment and social integration, which also increases the risk of mental health problems in adulthood. To address this gap, the Institut de Recerca Sant Pau (IR Sant Pau) is participating in the Aut-CARE project (Autism Cognitive-Affective REmediation for adults), aimed at improving not only access to work but also long-term job retention.

Developed in collaboration with the Friends Foundation and supported by the ”la Caixa” Foundation Connecta Call, the initiative focuses on the co-creation of an intervention program for young people and adults with ASD, with the goal of addressing both barriers to employment access and the challenges associated with maintaining employment over time. The project is based on a participatory approach that incorporates the direct experience of people with autism to adapt interventions to their real needs.

The magnitude of this issue is clearly reflected in the data. According to Autism Europe, between 76% and 90% of adults with ASD are unemployed, making this group the one with the highest unemployment rate among people with disabilities. Although organizations such as the Spanish Autism Confederation have identified labor market inclusion as a priority, barriers to access persist, largely due to the lack of evidence-based interventions tailored to the specific cognitive and emotional needs of autism, as well as the presence of generalist programs that do not address these characteristics.

A Three-Phase Project to Address an Unmet Need

During its first phase, the research team conducted an in-depth analysis of the socio-occupational situation of individuals aged 16 to 30 diagnosed with ASD, as well as their cognitive and emotional profile. This work led to the development of a comprehensive report of nearly 100 pages, which served as the foundation for guiding the next stage of the project.

“The first phase has allowed us to gain a very detailed understanding of the real difficulties these individuals face in their daily lives, both in the emotional domain and in executive functions, and how these directly impact their employment trajectories,” explains Maria Portella, head of the Mental Health Research Group at IR Sant Pau and one of the project leads.

Based on these findings, the team developed a second phase focused on the co-creation of the Aut-CARE program together with people with ASD. This participatory process, based on focus groups and qualitative analysis, made it possible to define key aspects such as the structure, content, and format of the intervention sessions.

One of the most relevant findings of the project is that difficulties are not limited to accessing employment but begin at this stage and intensify once a job is obtained. “Few people with autism manage to enter the labor market, and, in numerous instances, when they do, they face significant challenges in maintaining their position over time. This highlights the need to develop specific tools that support the entire process, not just access,” adds Maria Portella.

The Next Phase: Implementing and Evaluating the Program’s Impact

The resulting program, which includes group sessions focused on emotional regulation and cognitive skills training, will be implemented during the third phase of the project, scheduled before the summer. This stage allows its impact to be evaluated in a pilot study with participants.

From the Friends Foundation, a partner organization in the project, they highlight the value of this approach centered on real needs. “Co-creation with participants themselves has been key to ensuring that the solutions designed are truly useful and applicable in their daily lives,” says Susanna Díaz, director of the Friends Foundation.

The Aut-CARE project represents progress in the development of personalized interventions in the field of ASD, with an approach that integrates scientific evidence and the direct experience of users, aiming to tangibly improve their quality of life and social inclusion.

For nine years, Marta Brunet has been living with a sarcoma and has undergone seven surgeries at Hospital de Sant Pau. Rather than remaining a personal experience, she has taken a step further and decided to turn this journey into a collective action to support research into these tumors at the Institut de Recerca Sant Pau (IR Sant Pau). This initiative stems from direct contact with the disease and a desire to contribute to progress in a field that still faces significant clinical challenges.

The initiative took shape on February 21 with a padel tournament held simultaneously across all Aurial Group clubs. Driven by Brunet herself, the event brought together players and participants with a shared goal: to turn sport into a tool for supporting research. Registration fees and voluntary contributions from attendees made it possible to raise a total of €12,000, which will be allocated to projects developed by IR Sant Pau in this field.

Sarcomas are rare tumors but highly complex from a clinical perspective, which makes diagnosis and treatment difficult and requires sustained research efforts. In this context, initiatives like this help strengthen research lines aimed at improving knowledge of the disease and advancing the development of new therapeutic strategies.

Beyond fundraising, the initiative shows how a personal experience can become the driving force behind an action with collective impact. In this case, Marta Brunet’s journey not only gave rise to the project but also mobilizes a community that actively supports research and helps raise awareness of a disease that often remains in the background.

Irene Pascual-Latorre, a predoctoral researcher in the Cellular Immunotherapy and Gene Therapy group at the Institut de Recerca Sant Pau (IR Sant Pau) and the Hematology Department at Hospital de Sant Pau, was recognized with the award for one of the Best Young Poster Abstracts at the annual congress of the European Society for Blood and Marrow Transplantation (EBMT). The congress was held in Madrid from March 22 to 25, 2026. The work highlighted an innovative strategy to improve the efficacy of CAR-T therapies through pharmacological modulation during their ex vivo production, in a key research area for the development of more effective cellular therapies.

“Optimizing the characteristics of the CAR-T product is a key aspect in improving clinical outcomes. This work provides new approaches to modulate this process during its generation,” explains Irene Pascual-Latorre.

Optimizing CAR-T Cell Quality to Improve Clinical Efficacy

CAR-T therapies have represented a significant advance in the treatment of hematologic malignancies, although important challenges remain regarding the durability of response. In this context, the composition of the infused cellular product emerges as a determining factor, particularly the proportion of T cells with a stem memory phenotype (T_SCM), which is associated with greater expansion capacity and long-term persistence. Improving this cellular profile is therefore one of the most active strategies in the field.

The study focused on increasing this population through modulation of molecular signaling pathways involved in T-cell differentiation and expansion. Specifically, it analyzed the impact of PI3K and CBP/p300 inhibition during the ex vivo expansion of CAR-T cells targeting CD30 and CD19, with the aim of optimizing the functional characteristics of the final product.

Pharmacological Modulation During Ex Vivo Expansion

To this end, the team used T cells from patients with relapsed or refractory lymphomas, which were genetically modified to express CAR30 or CAR19. During the cell expansion process, different pharmacological treatments were applied—a PI3K inhibitor, a CBP/p300 inhibitor, and a combination of both—along with a control condition without treatment. Throughout the process, key parameters in CAR-T cells were evaluated, including cell viability, expansion capacity, the proportion of T_SCM cells, and antitumor activity against tumor cell lines.

“We have analyzed how different pharmacological interventions during ex vivo expansion can influence the balance between differentiation and proliferative capacity of CAR-T cells. These types of approaches allow for more precise tuning of the characteristics of the final product,” Pascual-Latorre notes.

Improved Memory Subpopulation Composition and Expansion Capacity

The results indicated that pharmacological modulation improved key characteristics of CAR-T products. PI3K inhibition promoted enrichment in T_SCM cells in CAR30-T cells, although with some impact on cytotoxic activity at higher doses. Meanwhile, CBP/p300 inhibition increased cell expansion capacity without affecting CAR30-T subpopulation differentiation or antitumor function.

The combination of both inhibitors achieved a balance between enhanced cell expansion and increased T_SCM phenotype without compromising short-term efficacy against tumor cells. In CAR19-T cells, CBP/p300 inhibition also improved expansion without inducing cellular differentiation or loss of antitumor activity, reinforcing the consistency of the findings across different experimental settings.

A Step Toward More Effective Cellular Therapies

The study concluded that targeted pharmacological inhibition during ex vivo production may help generate CAR-T products with greater therapeutic potential by optimizing their cellular composition and functionality. This approach is particularly relevant in the development of new strategies for patients with refractory disease, where incremental improvements in these therapies may have a significant clinical impact.

“Although these are preclinical results, the data provide a solid foundation for further exploring strategies to improve the efficacy of CAR-T therapies in the clinical setting,” Pascual-Latorre concludes.

The recognition received at the EBMT congress highlighted both the scientific quality of the work and its potential impact in the field of cellular immunotherapy, reinforcing the role of IR Sant Pau in the development of advanced therapies in hematology.

The therapeutic use of psychedelics continues to gain ground in psychiatry, particularly in the management of complex disorders such as treatment-resistant depression, where available options remain limited. In this context, a phase II clinical trial published in JAMA Psychiatry evaluated the efficacy and safety of GH001, an inhaled synthetic formulation of mebufotenin (5-MeO-DMT), a fast-acting psychedelic compound, in these patients. The study included Narcís Cardoner, Director of the Psychiatry Department at Hospital de Sant Pau and researcher in the Mental Health group at the Sant Pau Research Institute.

This fast-acting psychedelic compound is being investigated as a potential therapeutic alternative in psychiatric disorders, particularly due to its ability to produce rapid clinical effects after a single treatment session in patients with treatment-resistant depression. In this regard, Narcís Cardoner notes that “interest in psychedelics in mental health reflects the need to explore new therapeutic pathways in patients who do not respond to conventional treatments.”

The study included 193 patients with treatment-resistant depression who received GH001 via inhalation in a controlled clinical setting with structured psychological support. The design included the administration of repeated doses within a single session until achieving a defined therapeutic effect.

The results showed significant reductions in depressive symptoms following treatment, with a mean decrease of up to 15 points on the MADRS (Montgomery-Åsberg Depression Rating Scale), a widely used clinical tool to assess depression severity and changes after treatment. This magnitude of reduction is considered clinically meaningful in patients with treatment-resistant depression. In addition, approximately 57% of patients achieved a clinical response, and nearly 29% reached remission in the weeks following the intervention. The observed safety profile was consistent with that of other psychedelic compounds, with adverse events generally transient and manageable within the trial setting.

Based on these findings, Narcís Cardoner states that “this type of study helps consolidate interest in psychedelics as a potential therapeutic pathway in complex psychiatric disorders, although results should be interpreted with caution, as these are early-phase trials.”

The study also assessed the treatment’s safety profile, describing mostly transient adverse events that were manageable in the clinical trial context. However, these findings highlight the need for further research to determine the duration of the effect, optimal dosing, and the role of psychotherapeutic support in the observed response.

For Narcís Cardoner, beyond the specific results, the value of the study lies in its contribution to an emerging field. “Psychedelics are generating growing interest in clinical research, and studies like this help better define their potential and limitations, as well as lay the groundwork for larger and independent future trials.”

The management of treatment-resistant depression remains one of the major challenges in mental health, driving the exploration of new therapeutic strategies. In this context, research on psychedelics is consolidating as an area of growing interest, in which IR Sant Pau is strengthening its research activity with the aim of contributing to the development of new evidence-based options.

Reference Article:

Cubała WJ, Bajbouj M, Bauer M, Baune BT, Cardoner N, Devlin F, Doolin K, Dueñas Herrero RM, Elices M, Feeney A, Gałuszko-Węgielnik M, Jakuszkowiak-Wojten K, Janů L, Kelly JR, Ledden K, Maclsaac R, Madero S, McInerney SJ, Montejo AL, Nawka A, Páleníček T, Pérez Solà V, Ramaekers JG, Reif A, Ritter P, Ryan F, Svendsen CB, Sweeney C, Terwey TH, Trivedi MH, Valcheva V, Vieta E, Thase ME. GH001 vs placebo in patients with treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry 2026. https://doi.org/10.1001/jamapsychiatry.2026.0096

More than 90% of people with Down syndrome will develop symptoms of Alzheimer’s disease during their lifetime. And when epilepsy is added to that diagnosis, decline accelerates significantly. The LESS-AD study is a clinical trial jointly promoted by the Sant Pau Alzheimer Down Unit and IR Sant Pau to investigate whether preventing these epileptic seizures with a drug can slow disease progression. The trial is currently in the recruitment phase.

“Down syndrome involves a very significant genetic burden that determines the development of Alzheimer’s disease, and we have known this for some time. The appearance of epileptic seizures over the course of the disease is common and worsens its progression. What we are asking is whether, by acting before epileptic seizures appear, we can also slow the progression of Alzheimer’s disease,” explains Dr. María Carmona-Iragui, a researcher in the Neurobiology of Dementias group at IR Sant Pau and at the Sant Pau Memory Unit, who leads the study. “We are increasingly understanding how the disease progresses in this population, and this allows us to identify moments when an intervention could make a difference.”

A Triple Diagnosis That Accelerates Decline

The link between Down syndrome and Alzheimer’s disease has a well-established biological explanation: the triplication of chromosome 21 causes an overproduction of beta-amyloid protein, making this population vulnerable to the disease. However, the course of Alzheimer’s disease is not always the same. In many cases, epileptic seizures also appear over time—between 50% and 80% of people with Down syndrome and Alzheimer’s disease will develop them at some point—and when this occurs, cognitive and functional decline accelerates compared to those who do not experience seizures. This condition even has its own name: LOMEDS (Late-Onset Myoclonic Epilepsy in Down Syndrome), a late-onset form of epilepsy with distinct electroclinical features that is closely linked to Alzheimer’s progression in this population.

Despite the severity of this condition, people with Down syndrome have historically been underrepresented in clinical research. The complexity of working with this population—which requires specific adaptations in study design and close involvement of families and caregivers—has meant that many relevant questions remain unanswered. “We know a great deal about how the disease evolves in this population, but for too long this has not translated into clinical trials that seek real solutions,” notes Dr. Carmona-Iragui. “This study is a commitment to changing that.”

The Hypothesis: Acting Before Seizures Appear

The LESS-AD study is based on a novel therapeutic hypothesis: administering levetiracetam preventively, before the first epileptic seizure occurs, could not only reduce the risk of seizures but also help slow the progression of Alzheimer’s disease in this population. Levetiracetam is an antiepileptic drug widely used in clinical practice, with decades of experience and a well-established safety profile, making its evaluation in a preventive context feasible.

Participants in the trial will receive levetiracetam or placebo tablets for 96 weeks. Throughout the study, periodic clinical assessments will be conducted, including medical examinations, laboratory tests, brain magnetic resonance imaging, electroencephalography, and memory and cognitive function tests.

Who Can Participate?

The trial is open to adults with Down syndrome who have already shown early symptoms of Alzheimer’s disease but have not experienced any epileptic seizures. It is precisely within this window—after the onset of initial cognitive symptoms and before the first seizures occur—that the research team believes the greatest opportunity for intervention may exist. Participants must have a caregiver with daily contact who can accompany them to follow-up visits, which take place every six months at several centers in Spain: Barcelona, Madrid, Donostia, Santander, and Granada.

The LESS-AD study is an academic-initiated trial, without funding or sponsorship from the pharmaceutical industry, highlighting IR Sant Pau’s commitment to independent research in the service of patients. This type of study is particularly relevant in the context of Down syndrome, a population historically underrepresented in clinical drug trials despite the high prevalence of serious comorbidities such as Alzheimer’s disease.

The IR Sant Pau Alzheimer Down Unit, created in 2014 in collaboration with the Catalan Down Syndrome Foundation, is a pioneering clinical care and research unit worldwide in the care of adults with Down syndrome and Alzheimer’s disease. It is also the only unit of its kind in Spain, recognized by the Government of Catalonia as a reference unit in Catalonia for neurological conditions associated with Down syndrome. In addition, the Sant Pau Memory Unit has recently been designated by the Spanish Ministry of Health as a CSUR center—Center, Service, and Unit of Reference of the National Health System—for rare diseases associated with cognitive disorders.

IR Sant Pau’s leadership in this field has led to the development of one of the most important international reference cohorts for the study of Alzheimer’s disease in Down syndrome: the DABNI project (Down Alzheimer Barcelona Neuroimaging Initiative), which has enabled the publication of relevant findings in leading journals such as The Lancet and Brain.

What has long been interpreted as permanent and irreversible vascular damage may not be exclusively so. In people with Down syndrome—one of the most robust populations for studying Alzheimer’s disease due to the near-universal presence of the characteristic proteinopathies of this dementia from the age of 40—some lesions visible on magnetic resonance imaging do not follow a linear course. A longitudinal study from the Institut de Recerca Sant Pau (IR Sant Pau), published in Alzheimer’s & Dementia, shows that these alterations can fluctuate and even decrease over time in the Down syndrome population. This is especially true once the clinical symptoms of Alzheimer’s disease have begun to manifest.

The study analyzed the evolution of white matter hyperintensities (WMH), lesions typically associated with cerebral vascular alterations that appear as brighter areas on magnetic resonance imaging. These alterations are considered a marker of small vessel disease and have been linked to cognitive impairment in different contexts.

Previous studies from IR Sant Pau had shown that, in people with Down syndrome, the burden of these lesions increases with age and is associated with characteristic Alzheimer’s biomarkers, such as beta-amyloid and phosphorylated tau proteins. However, those studies were cross-sectional and provided a snapshot of the disease at different time points, without allowing observation of its evolution within the same individuals.

“The cross-sectional analysis gives us a snapshot of each stage of the process, but it does not show how these alterations change within each individual over time. With this study, we were able to see the movie and confirm that the trajectory is not always linear,” explains Alejandra Morcillo-Nieto, researcher in the Brain Imaging and Aging group at IR Sant Pau and first author of the article.

Following the Same Individuals to Understand True Evolution

The study included 80 adults with Down syndrome and 53 neurotypical adults as a control group, all of whom had at least two magnetic resonance scans separated by a minimum of six months. At baseline, 65 participants with Down syndrome were in the asymptomatic stage of Alzheimer’s disease, and 13 were in the symptomatic stage—prodromal or dementia. During follow-up, ten initially asymptomatic individuals progressed to symptomatic stages, allowing researchers to analyze structural changes across different points of the clinical continuum.

Unlike previous cross-sectional studies, this work made it possible to calculate the annual change in WMH volume in the same individuals over time. The analysis was conducted both globally and by specific brain regions—frontal, parietal, temporal, and occipital lobes; basal ganglia; and periventricular areas—using a longitudinal segmentation methodology designed to detect true changes and minimize potential technical variability between scans.

The results indicated that up to approximately age 40, changes were minimal and relatively stable. From that age onward—when virtually all individuals with Down syndrome already present cerebral amyloid pathology—greater variability in the evolution of these lesions began to emerge. Over an approximate interval of two to three years, the predominant trajectory was not progressive increase but rather a heterogeneous evolution, in which a relevant proportion of individuals who already had WMH experienced measurable reductions.

“When we saw that a relevant percentage of participants showed a reduction, we realized that we could no longer interpret these lesions as something fixed and irreversible. At certain points, their behavior is more dynamic than we previously thought,” notes Alejandra Morcillo-Nieto.

A More Pronounced Reduction Once Symptoms Are Present

The analysis strongly suggested that the annual decrease in WMH volume was significantly greater in individuals with clinical symptoms of Alzheimer’s disease than in those in the asymptomatic stage and in controls. In other words, the decline was not observed in the early stages but rather when the disease had already become clinically manifest.

While asymptomatic participants showed minimal changes and a relatively stable trajectory during follow-up, the symptomatic group exhibited more pronounced reductions. “In people with Down syndrome, it is estimated that by around age 40, virtually all already have Alzheimer’s pathology, although symptoms appear later. The fact that this greater variability and reduction coincides with that stage is temporally very significant,” explains Alejandra Morcillo-Nieto.

Differences were particularly evident in parietal and occipital regions and in periventricular areas, locations that previous IR Sant Pau studies had already identified as particularly affected in this population. The fact that the greatest instability is concentrated in these regions reinforces the idea that WMH may reflect processes linked to the interaction between amyloid burden, vascular alterations, and clinical progression, rather than a simple linear accumulation of damage.

Possible Mechanisms: Neurodegeneration, Inflammation, and Amyloid Angiopathy

To understand this phenomenon, the team explored different possible biological mechanisms that could explain why, in a relevant proportion of participants, hyperintensities decreased over time. In some cases, the reduction could be associated with white matter atrophy linked to neurodegeneration. However, this explanation was not sufficient for all observed cases, suggesting the involvement of additional processes.

In this regard, there is increasing evidence that inflammation in the brain plays an important role. In Down syndrome, this inflammation may have several origins: alterations of the immune system inherent to trisomy 21, the accumulation of abnormal proteins such as amyloid (related to Alzheimer’s disease), and changes in cerebral blood vessels.

The analysis indicated that the presence of cerebral microbleeds—a marker of cerebral amyloid angiopathy—was associated with a greater longitudinal reduction in hyperintensities. This finding points to a possible role of vascular changes related to amyloid deposition in the dynamics of these lesions. “In Down syndrome, amyloid does not only accumulate in brain tissue but also in the vessels. This can alter the barrier that protects the brain and allow fluid leakage, generating a signal visible on MRI. If this inflammatory process improves, that signal may decrease in subsequent scans,” explains Alejandra Morcillo-Nieto.

Regardless of the cause, inflammation in the brain may contribute to the appearance of these lesions, but it may also decrease over time, which would explain why in some cases hyperintensities subsequently decline. Overall, the data suggest that these hyperintensities do not always follow a linear course, but rather reflect dynamic processes in which neurodegeneration, inflammation, and vascular changes interact.

Relationship With Alzheimer’s Biomarkers

The study also analyzed the relationship between the annual change in WMH volume and different Alzheimer’s disease biomarkers in cerebrospinal fluid and plasma, including beta-amyloid and phosphorylated tau proteins. Previous cross-sectional studies from IR Sant Pau had shown that a higher lesion burden was associated with alterations in these biological markers. However, in the longitudinal analysis, no robust significant associations were identified between annual WMH volume variation and changes in these biomarkers.

This result clearly differentiates longitudinal findings from cross-sectional ones. Researchers note that this lack of association may be masked by the inherent complexity and clinical heterogeneity during adulthood in Down syndrome, where biomarker trajectories are not linear and depend on disease stage.

“In cross-sectional analyses, we found associations between lesion burden and Alzheimer’s biomarkers. But when we evaluate how these lesions change year by year in the same individuals, that relationship does not appear with the same consistency. This may reflect that the evolution of these markers has quite unfamiliar and non-linear phases throughout adulthood,” explains Alejandra Morcillo-Nieto.

A Reflection of Alzheimer’s Complexity

Overall, the findings underscore that Alzheimer’s disease—even in a genetic model as well defined as Down syndrome—does not follow simple or linear trajectories. The evolution of WMH does not respond to an exclusively cumulative pattern but rather shows phases of stability, increase, or even reduction, depending on the clinical moment and biological context.

This dynamic behavior reinforces the idea that in the brain multiple processes coexist and may interact over time: amyloid accumulation, vascular changes, inflammatory phenomena, and neurodegeneration do not necessarily progress at the same rate or with the same intensity.

“These results force us to rethink how we interpret white matter hyperintensities in the context of Alzheimer’s disease. We cannot automatically assume that every increase or decrease responds to the same mechanism, because the brain is undergoing different processes at the same time. That is why it is essential to study the disease longitudinally: only by following the same individuals over time can we truly understand what is happening,” says Dr. Alexandre Bejanin, head of the Brain Imaging and Aging group at IR Sant Pau and senior author of the study.

Implications for Research and Therapies

These findings are particularly relevant in the current context of developing therapies targeting the amyloid protein. Some of these interventions may be associated with radiological alterations linked to cerebral amyloid angiopathy, making it essential to understand how these lesions evolve in the absence of treatment.

“At a time when anti-amyloid therapies are being developed and evaluated, it is essential to understand the natural history of these lesions in Down syndrome,” says Dr. Alexandre Bejanin. “Knowing that these lesions show natural fluctuations requires us to be highly precise in clinical trials. If we can separate the true effect of treatment from the biological progression of the disease, we will be able to properly evaluate drugs and identify our ideal intervention window—that is, when is the best time to initiate these therapies safely and effectively.”

In this sense, the study provides a necessary basis for more accurately interpreting radiological changes in future clinical trials and opens new lines of research into the biological mechanisms underlying this variability.

Reference Article:

Morcillo-Nieto AO, Rozalem-Aranha M, Maure-Blesa L, Rodríguez-Baz Í, Arriola-Infante JE, Franquesa-Mullerat M, Zsadanyi SE, Vaqué-Alcázar L, Parra JA, Zhao Z, Arranz J, Videla L, Barroeta I, Del Hoyo Soriano L, Benejam B, Fernández S, Hernandez AS, Pertierra L, Giménez S, Alcolea D, Belbin O, Lleó A, Carmona-Iragui M, Fortea J, Bejanin A. Temporal dynamics of white matter hyperintensities related to Alzheimer’s disease in adults with Down syndrome. Alzheimers Dement 2026;22:e71157. https://doi.org/10.1002/alz.71157

Tauopathies, a group of neurodegenerative diseases that includes progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), remain one of the major diagnostic challenges in neurology today. In their early stages, they can present with highly diverse symptoms and overlap with other neurodegenerative disorders, making it difficult to accurately identify the underlying disease and delaying the development of treatments aimed at modifying its course.

A project led by Dr. Jesús García-Castro, a researcher at the Institut de Recerca Sant Pau (IR Sant Pau) and a neurologist at the Sant Pau Memory Unit, has received a Next-Generation Research Grant in Frontotemporal Dementia. This is an international grant promoted by the American Academy of Neurology Institute, the American Brain Foundation, and The Association for Frontotemporal Degeneration. The award will fund a two-year study focused on the development and validation of new biomarkers to improve the diagnosis and monitoring of these diseases.

“One of the major challenges in these disorders is that the definitive diagnosis still depends, in numerous instances, on neuropathological examination,” explains Dr. Jesús García-Castro. “Having reliable biomarkers that allow the disease to be identified during a patient’s lifetime is an essential step toward improving clinical management and advancing the development of new treatments.”

Blood Biomarkers and Neuroimaging

The project proposes an innovative strategy based on the combination of blood biomarkers and advanced magnetic resonance neuroimaging analysis, with the aim of improving the identification of tauopathies in the early stages of the disease. Specifically, the study will analyze the presence of different isoforms of the tau protein in extracellular vesicles present in plasma, small particles released by cells that transport proteins and other molecules. This can reflect pathological processes occurring in the brain. The proportion of tau isoforms associated with these vesicles could provide relevant information about the type of neurodegenerative pathology present in each patient.

These data will later be integrated with structural magnetic resonance imaging analysis models capable of identifying specific patterns of brain atrophy in cortical and subcortical regions involved in tauopathies. The combination of both approaches will allow the development of a two-stage diagnostic algorithm to facilitate a more precise identification of these diseases.

“Each of these tools provides different information about the disease. Integrating blood biomarkers and neuroimaging data can help us better understand the biological mechanisms of tauopathies and improve their identification in clinical practice,” explains García-Castro.

International Cohorts and Longitudinal Follow-Up

The study will rely on the analysis of data from large international research cohorts in neurodegenerative diseases, including participants from initiatives such as 4RTNI, UCSF, and the SPIN (Sant Pau Initiative on Neurodegeneration) cohort. Longitudinal analysis of these patients will allow researchers to evaluate not only the diagnostic performance of the biomarkers but also their usefulness in predicting the clinical progression of the disease and better understanding the factors that influence its progression.

“These types of tools can also be key for clinical research, because they will allow us to identify patients more precisely and better track disease progression,” says García-Castro. “This is especially relevant for the development of future clinical trials aimed at modifying the course of these disorders.”

Advancing Research in Frontotemporal Dementias

The Next-Generation Research Grant in Frontotemporal Dementia is an international initiative aimed at supporting investigators in the early stages of their scientific careers and promoting advances in the understanding of frontotemporal dementias.

The project will be carried out within the multidisciplinary environment of IR Sant Pau, under the mentorship of Dr. Ignacio Illán-Gala, an expert in neuroimaging biomarkers and neurodegenerative diseases, and with the participation of researchers from the Sant Pau Memory Unit. This is within the framework of research lines dedicated to the study of frontotemporal dementias and other neurodegenerative diseases.

In acute myeloid leukemia, one of the main challenges is preventing relapse: although many patients respond to the initial treatment, leukemic stem cells capable of reactivating the disease may persist. To address this problem, Dr. Ugutz Unzueta, a researcher in the Oncogenesis and Antitumor Drugs Group at the Sant Pau Research Institute (IR Sant Pau), is leading the development of a precision nanoimmunotherapy designed to eliminate these resistant cells selectively. The project is supported by the Miquel Rutllant Fellowship, endowed with €100,000 and lasting two years, which has just been renewed for its second year following an event organized by the Fundació d’Investigació Salut i Progrés (FISP).

During the renewal meeting, Dr. Unzueta presented the progress achieved during the first year of work and outlined the next stages of a research effort aimed at improving patient prognosis through more selective and potentially less toxic therapies.

The Miquel Rutllant Fellowships aim to support biomedical research projects with potential clinical impact and to promote the development of new therapeutic strategies against complex diseases. These grants help consolidate innovative research lines and generate results that may later be translated into clinical practice.

The Challenge of Eliminating Leukemic Stem Cells

Acute myeloid leukemia is a rare hematological malignancy characterized by the uncontrolled proliferation of immature cells in the bone marrow. Although many patients initially respond to induction chemotherapy, a significant proportion may experience relapse due to the persistence of leukemic stem cells that remain anchored and protected within the bone marrow microenvironment.

“Our goal is to directly target the origin of relapse. If we manage to eliminate the leukemic stem cells that survive treatment, we could significantly change the prognosis for these patients,” explains Dr. Unzueta.

Among the mechanisms that promote the survival of these cells is the CXCR4 receptor, which is involved in their interaction with the bone marrow microenvironment. It is associated with poorer prognosis and a higher risk of relapse when expressed at high levels. The strategy developed by the IR Sant Pau team uses multivalent protein nanoconjugates capable of specifically recognizing cells that express CXCR4. These nanoparticles act as precision delivery vehicles and carry a highly cytotoxic molecule that is released once the nanoconjugate has been internalized by the tumor cell.

“This technology allows us to deliver a very potent drug directly to leukemic cells expressing CXCR4, increasing treatment efficacy and potentially reducing damage to healthy tissues,” the researcher notes.

Toward Personalized Therapies for Leukemia

At this stage of the project, the team will evaluate the activity of the nanoconjugate in samples from patients with acute myeloid leukemia obtained at Hospital de Sant Pau. The objective is to determine the level of CXCR4 expression required to observe a therapeutic effect and, in doing so, move toward a model for selecting patients with the highest likelihood of response.

In addition, the researchers will study its efficacy in immunocompetent murine models and its ability to induce immunogenic cell death, a mechanism that could help activate the immune response against leukemic cells. Its potential in combination with immune checkpoint inhibitors will also be explored to identify therapeutic strategies with possible synergistic effects.

“If we can confirm these results, we could move toward much more selective and personalized therapies specifically targeting the cells responsible for relapse in acute myeloid leukemia,” concludes Dr. Unzueta.

Maria Antentas, a nutritionist and predoctoral researcher in the Endocrinology, Diabetes, and Nutrition research group at the Sant Pau Research Institute (IR Sant Pau), has been awarded a FI-STEP 2025 predoctoral grant, granted by the Agency for Management of University and Research Grants (AGAUR). This was the only grant awarded to IR Sant Pau in this call. Thanks to this funding, the researcher will carry out her doctoral thesis over a period of three years under the supervision of Dr. Dídac Mauricio and Dr. Marina Idalia Rojo López.

The FI-STEP grants aim to promote the training of predoctoral researchers by supporting the hiring of young researchers so they can carry out their doctoral thesis in strategic areas defined by the European Union. Through this program, the goal is to strengthen the scientific and technological capacity of the research system by promoting high value-added projects with potential social, economic, and scientific impact.

Maria Antentas’s research project focuses on the study of lipid metabolism and dietary fatty acid intake, as well as the full set of lipids present in the body, including the lipidome and the advanced lipoprotein profile. The main objective is to deepen the understanding of how these lipid profiles are associated with the risk of developing liver diseases such as steatosis and liver fibrosis, especially in people with type 1 and type 2 diabetes. This also occurs in individuals without diabetes.

The research will incorporate a gender perspective and will analyze potential differences between men and women regarding lipid metabolism, diet, and the risk of liver involvement. Using advanced lipidomics, bioinformatics, and lipoprotein profile analysis techniques, the project aims to further identify possible noninvasive biomarkers associated with the risk of liver disease linked to metabolic dysfunction.

The results of this project could help improve understanding of the mechanisms involved in liver disease associated with diabetes and reinforce the role of nutrition and personalized dietary approaches as key tools for its prevention and management. In addition, the research aligns with European priorities in the fields of biotechnology and bioinformatics and reinforces IR Sant Pau’s commitment to biomedical research of excellence with clinical and social impact.

A new international methodological guideline from the GRADE group (Grading of Recommendations Assessment, Development, and Evaluation) has updated the criteria for developing and using so-called good practice statements in clinical practice and public health guidelines. The document, published as a special article in Annals of Internal Medicine, one of the most influential medical journals worldwide, seeks to avoid the inappropriate or excessive use of this type of statement and improve its justification, transparency, and credibility.

Researchers from the Clinical Epidemiology and Health Services Research Group at the Institut de Recerca Sant Pau (IR Sant Pau) participated in the development of this update, together with investigators from the Iberoamerican Cochrane Center, an institution affiliated with IR Sant Pau. Among the authors are Dr. Pablo Alonso, a researcher at IR Sant Pau, as well as Drs. David Rigau and Carlos Canelo from the Iberoamerican Cochrane Center.

Good practice statements are reserved for interventions considered so obvious, essential, or ethically unquestionable—such as basic safety measures or respect for fundamental ethical principles—that conducting a formal systematic review of the evidence is not considered appropriate. However, in practice, these statements have sometimes been used to formulate recommendations without an explicit evaluation of the available evidence.

“For years we have seen good practice statements included in some guidelines without sufficiently explicit justification,” explains Dr. Pablo Alonso. “This can create confusion and, in the long term, undermine confidence in the recommendations, even when they aim to reinforce good practices.”

According to the researcher, the main objective of this update is “to help guideline developers more clearly distinguish when a recommendation can truly be considered a good practice and when, instead, it should undergo a formal evaluation of the evidence.”

A Clearer Definition and a New Three-Category Classification

The new methodological guidance proposes a revised definition of good practice statements and classifies them into three main categories, according to their primary foundation: those based on ethical principles and human rights; those grounded in widely accepted essential practices or principles; and those supported by strong and well-established scientific evidence.

This classification makes it possible to better contextualize each statement and explicitly clarify the reasoning behind it. “The goal is not to restrict their use, but to use these statements only when they are truly justified and to clearly document why they are formulated,” Alonso notes. “In this way, guidelines gain methodological consistency, transparency, and credibility.”

In addition, the guidance explicitly incorporates consideration of key decision-making criteria, such as potential benefits and risks, practical consequences, values and preferences, and resource implications. “Introducing these criteria systematically helps ensure that decisions are not perceived as arbitrary, but rather as the result of a reflective and structured process,” adds Dr. Alonso.

Practical Tools to Improve Transparency and Reproducibility

The article includes step-by-step practical examples and presents a structured tool that helps guideline development teams determine when it is appropriate to formulate a good practice statement and how to report it clearly, transparently, and reproducibly.

“We wanted to provide concrete and applicable tools, not just theoretical principles,” emphasizes Dr. Alonso. “The intention is for guideline development teams to apply this guidance easily and consistently, regardless of the clinical or public health context.”

The work builds on the authors’ methodological experience within the framework of the European Commission Initiative on Colorectal Cancer (ECICC), a project aimed at improving the quality and harmonization of clinical guidelines in this field.

For Dr. Alonso, this update has direct relevance for practice: “Clinical guidelines have a very significant influence on decision-making. Ensuring that even recommendations considered ‘obvious’ are well justified is key to maintaining the trust of professionals, policymakers, and patients.”

This new guidance is particularly relevant for those who develop, adapt, or implement evidence-based guidelines—an activity that is central to the Cochrane community and to public health decision-making. Its application may help reduce the inappropriate use of good practice statements and strengthen the methodological quality and transparency of clinical recommendations.

Reference Article:

Dewidar O, Akl EA, Morgano GP, Parmelli E, Saz-Parkinson Z, Langendam MW, Meerpohl JJ, Marti M, Mayer M, Djulbegovic B, Brignardello-Petersen R, Chu DK, Murad MH, Canelo-Aybar C, Mathew JL, Alonso-Coello P, Qaseem A, Schwingshackl L, Bognanni A, Rojas-Reyes MX, Morgan RL, Klugar M, Rigau Comas D, Stallings E, Iorio A, Tugwell P, Darzi A, Turgeon AF, Shamliyan TA, Munn Z, Mathioudakis AG, Piggott T, Lotfi T, Pottie K, Guyatt G, Schünemann HJ. GRADE guidance: Update on developing good practice statements in guidelines. Ann Intern Med 2026. https://doi.org/10.7326/ANNALS-25-00431.

The Spanish Congress of Deputies hosted on last February 13 a parliamentary session focused on psychedelic-assisted therapies and their possible development in the field of mental health in Spain. The session featured the participation of Dr. Narcís Cardoner, head of the psychiatry department at Hospital de Sant Pau and researcher of the Mental Health group at the Sant Pau Research Institute (IR Sant Pau).

The session, held in the Ernest Lluch Room, brought together researchers, clinical professionals, regulatory experts, and institutional representatives with the aim of analyzing the current state of available scientific evidence. The existing barriers to research in this field, and the regulatory challenges associated with a potential incorporation of these therapies into the healthcare system.

During the presentations, the recent evolution of international clinical trials with psychedelic substances was reviewed, covering indications such as treatment-resistant depression, post-traumatic stress disorder, and certain addictions. Experts emphasized that, while preliminary results are promising in controlled clinical settings, it is essential to consolidate the evidence through rigorous studies with sound methodological designs, strict safety criteria, and medium- and long-term follow-up.

The debate also highlighted the administrative and regulatory difficulties that currently constrain the development of this line of research in Spain. It also highlighted the need to establish clear regulatory frameworks that allow progress to be made with scientific, ethical, and healthcare guarantees. In this regard, issues related to the specialized training of clinical teams, center accreditation requirements, and institutional oversight of therapeutic programs were addressed.

In his presentation, Dr. Cardoner brought the clinical and scientific perspective of the IR Sant Pau Mental Health group, which conducts research in this field from a strictly biomedical and evidence-based approach. His team is the first in Spain to hold an independently funded grant to study the use of psychedelics in mental health, positioning the institute as a key player in the national research landscape.

IR Sant Pau’s participation in this parliamentary hearing reinforces its commitment to rigorous clinical research and to an informed institutional debate on new therapeutic strategies to address mental disorders that continue to represent a major healthcare and social challenge.