A study conducted by researchers at the Research Institute from Hospital Santa Creu i Sant Pau – IIB Sant Pau in Barcelona, Spain, has shown that deep brain stimulation of the subcallosal cingulate gyrus (SCG-DBS) can offer significant and lasting benefits for treating depression. The results of this research support the idea that this surgical intervention could be an effective alternative for patients suffering from severe major depression who have not responded to conventional treatments.

The study, published today in The Journal of Clinical Psychiatry, is the longest follow-up of patients conducted in Europe to date, analyzing clinical factors related to the long-term benefits and safety of deep brain stimulation of the subcallosal cingulate gyrus in treatment-resistant depression, as explained by Dr Javier de Diego and Dr Dolors Puigdemont, researchers in the Mental Health Research Group at IIB Sant Pau and psychiatrists at the same hospital.

A significant cause of disability and loss of quality of life

Depression is a disease that ranks among the leading medical causes of disability. It is estimated to affect nearly 300 million people worldwide. Conventional treatments generally yield good results, but it is estimated that 15 to 20% of patients do not respond adequately and show a more chronic and treatment-resistant course. These forms of treatment-resistant depression present a much higher risk of functional disability and have higher rates of complications and even mortality. Moreover, they have a much greater impact on quality of life.

“In these cases, in addition to combining pharmacological treatment with psychotherapy, we have the option of using combination or augmentation strategies with drugs and molecules that act through different mechanisms of action. We can even opt for interventions such as electroconvulsive therapy for the most severe cases. However, there is a small subgroup of more severe patients who either cannot tolerate these treatments or stop responding to these strategies, experiencing recurrences and frequent hospitalizations or a persistent chronic course. In these cases, deep brain stimulation can be a hopeful alternative,” says Dr de Diego.

This study analyzed data from sixteen patients with treatment-resistant major depression, diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV or DSM-5), who received chronic deep brain stimulation of the subcallosal cingulate gyrus for a period of up to 11 years, from January 2008 to June 2019. Demographic, clinical, and overall functioning data were collected before surgery and during follow-up.

One of the most notable aspects, according to the psychiatrist from Sant Pau, is that patients showed sustained clinical improvements after the intervention, as measured by the 17-item Hamilton Depression Rating Scale (HAM-D17), the Clinical Global Impression, and the Global Assessment of Functioning.

The results demonstrate a significant decrease in depressive symptoms over time. As detailed by Dr de Diego, up to 75% of patients responded to treatment, and 50% ultimately achieved remission, meaning a reduction in symptoms below the threshold considered pathological, although not everyone could achieve complete functional recovery. “The repercussions of severe chronic depression are highly pronounced from a personal, social, and occupational perspective, and in many cases condemn individuals to a limited and isolated life for years,” explains Dr Puigdemont.

“A decrease in the frequency of depressive recurrences or an attenuation of symptom intensity are already very significant milestones for these individuals. In fact, in our sample, 40% of the treated patients achieved satisfactory levels of functional recovery, allowing them to enjoy their leisure time or engage in social and family life again, in some cases as they did before the onset of the illness,” explains the expert.

The effects are not immediate but are usually perceived within the first few months. Specifically, 55% of patients achieved remission an average of 139 days after the surgical intervention, according to the experts from Sant Pau.

In conclusion, deep brain stimulation of the subcallosal cingulate gyrus produced significant and lasting improvement in the majority of the patients studied, reinforcing the possibility that this technique may be an alternative for those suffering from treatment-resistant major depression when all other alternatives have been exhausted. “One of the current challenges is to identify clinical and neurobiological predictors of response in order to anticipate which cases of depression could benefit the most and determine the most appropriate parameters for deep brain stimulation in a more early and precise manner,” says Dr de Diego.

Deep brain stimulation is a technique that involves the implantation of ultra-thin electrodes in the brain, connected to small wires that run under the skin and reach a neurostimulator—similar to a pacemaker—that is usually placed in the pectoral or abdominal region. This neurostimulator generates electrical impulses whose parameters can be modified using an external controller until the desired response is observed. “The subcallosal cingulate cortex is a key brain region in depression. Evidence suggests that modulating the electrical activity in this region through deep stimulation can restore the functioning of brain circuits that are crucial in the persistence of these more severe and treatment-resistant depressive episodes,” explains Dr de Diego.

“The placement of the electrodes requires a thorough prior neuroimaging study and a surgical intervention that requires high precision and complexity, so multidisciplinary work between psychiatrists and neurosurgeons is essential. Subsequently, especially during the early post-intervention stage, it is necessary to closely monitor these patients, who require a comprehensive pharmacological, psychotherapeutic, and rehabilitative intervention plan,” reminds Dr Puigdemont.

In this study, researchers from the Mental Health Research Group at IIB Sant Pau, led by Dr Maria Portella, and several professionals from the Psychiatry Department of the same hospital, directed by Dr Narcís Cardoner, have worked closely with neurosurgeons Dr Rodrigo Rodríguez-Rodríguez and Dr Juan A. Aibar-Durán to provide this therapeutic alternative aimed at patients with the most severe affective disorders.

Reference article

• Carlo Alemany, Dolors Puigdemont, Ana Martín-Blanco, Rodrigo Rodríguez-Rodríguez, Juan A. Aibar-Durán, Muriel Vicent-Gil, Enric Álvarez, Víctor Pérez, Maria J. Portella, Javier de Diego-Adeliño. Response and Safety Outcomes in Treatment-Resistant Depression After Subcallosal Cingulate Gyrus Deep Brain Stimulation: Long-term Follow-up Study. J Clin Psychiatry 2023;84(0):22m14622

On the occasion of World ALS Day (June 21st), last Tuesday, June 20th, the event “Unzué and Sant Pau, a team against ALS” took place at the Modernist Site, featuring the participation of Juan Carlos Unzué, Dr. Ricard Rojas, neurologist, researcher, and coordinator of the ALS Functional Unit at Sant Pau, and Esther Sellés, director of the Miquel Valls Catalan ALS Foundation.

In a relaxed and enjoyable atmosphere, the event unfolded as a conversation between Juan Carlos Unzué, Dr. Ricard Rojas, and journalist Cristina Puig, with the incorporation of Esther Sellés, director of the Miquel Valls Catalan ALS Foundation.

At the beginning, a video was screened showing a routine visit by Juan Carlos Unzué to the Hospital de Sant Pau, where he was diagnosed in 2018 by the ALS Functional Unit led by Dr. Ricard Rojas. Due to the specific needs of the unit’s users, the team consists of different profiles, including neurologists, nurses, pulmonologists, rehabilitators, speech therapists, dieticians, social workers, and psychologists. Thanks to this multidisciplinary team, a comprehensive approach to the disease is achieved, providing the most complete assistance and treatment to patients, meeting their main goals of rapid diagnosis and decision-making focused on the specific needs of each patient.

During the conversation, various important issues related to the disease were addressed. Both Dr. Rojas and Juan Carlos Unzué agreed that the moment of diagnosis is one of the most crucial. On one hand, as Dr. Rojas explained, it is “the moment when the doctor-patient relationship is established,” a relationship that will be key throughout the entire process. As a doctor, Rojas explained that it is also one of the most challenging moments and that to do it as best as possible, it is essential to know the person who will receive the news, once again highlighting the importance of providing the closest and most humane care possible. The following video shows Dr. Rojas explaining how to deliver the diagnosis news for ALS.

THE IMPORTANCE OF ACCEPTANCE

Juan Carlos Unzué, from his point of view, explained that the warlike and fighting terminology often used in the disease is not the most appropriate. Instead, he said, “if I had to give advice to a person recently diagnosed with ALS, I would tell them that the most important concept is acceptance.” Sometimes many patients go through a stage of denial, but Juan Carlos Unzué emphasized that accepting the disease has allowed him to make the most of the possibilities in the new situation that the diagnosis placed him in, and thus, enjoy life to the fullest within the circumstances. This is one of the reasons why he has become a role model for many other people affected by ALS, and the following video is the best proof of how attitude towards the disease is essential.

FUTURE CHALLENGES OF ALS

After much experience in addressing and researching this disease, Dr. Rojas, who is also a researcher in the Neuromuscular Diseases Group at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant-Pau, states that “ALS is not a single disease, but the end stage of many different alterations that cause this high variability of symptoms and progression among patients.” Therefore, “in future research and approach, it is crucial to identify these alterations and classify patients into subgroups according to the typology they present in each case. Knowing what types of alterations cause neurodegeneration will allow us to offer more personalized treatment and also open new research avenues that will enable us to develop treatments capable of radically changing the course of the disease, which we do not have today and is crucial.”

Finally, the event concluded with interventions from some of the attendees, ALS patients, caregivers, and companions, who shared their experiences with Juan Carlos Unzué and the rest of the audience. In this video, you can watch the entire event from beginning to end on June 20th.

El Centre per a la Integració de la Medicina i les Tecnologies Innovadores (CIMTI) ha celebrat la jornada Crida Repte CIMTI 2023, que busca posar en valor la innovació del sistema sociosanitari català i que enguany s’ha enfocat a la promoció de la salut de la dona.

En el disseny i definició d’aquest repte han col·laborat les coordinadores del nou programa transversal de recerca en Salut de la Dona i Gènere de l’IIB Sant Pau, la Dra. Elisa Llurba, cap del grup de medicina perinatal i de la dona a l’IIB Sant Pau i directora del servei de ginecologia i obstetrícia a l’Hospital de Sant Pau, i la Dra. Ma Rosa Ballester, cap de la unitat de Recerca i Innovació Responsable a l’IIB Sant Pau. També les investigadores Dra. Rosa Corcoy, del Grup de Recerca en Endocrinologia, Diabetis i Nutrició, i la Dra. Virtudes Céspedes, cap del Grup de Recerca en Oncologia Ginecològica i Peritoneal.

Durant aquesta jornada en què s’ha presentat el repte determinat pels agents del sistema de salut i social de Catalunya i dirigit a propostes creades per equips multidisciplinaris, també ha assistit la cap de l’oficina Més Sant Pau, Patricia Pesudo.

Sant Pau està fent una clara aposta per fomentar la perspectiva de gènere en totes les seves àrees i grups d’investigació. Una mostra d’això és el programa transversal de recerca en Salut de la Dona i Gènere, creat en el marc del Pla de Recerca i Innovació Responsable (RRI). L’IIB Sant Pau està implementant accions adreçades a fomentar la incorporació de la perspectiva de gènere en el contingut de la recerca i a promoure la investigació específica de gènere per cobrir els buits de coneixement, posant en marxa els mitjans i recursos necessaris per facilitar-ho.

Dr. Roser Torra Balcells, coordinator of Hereditary Kidney Diseases at Fundació Puigvert and researcher in the Nephrology group at the Sant Pau Research Institute (IIB Sant Pau), has been appointed President-elect of the European Renal Association (ERA), during the 60th ERA Congress in Milan (June 15-18, 2023). Starting in 2024, she will preside over this international scientific association, which has 20,000 members, for a period of three years.

Dr. Roser Torra is a specialist in Nephrology, an expert in hereditary kidney diseases, and coordinator at Fundació Puigvert for various research networks on rare diseases, such as ERKnet and XUEC, as well as the Hereditary Kidney Diseases group of the Spanish Society of Nephrology (SEN) and the Catalan counterpart. She has also been a center coordinator in previous Nephrology research networks (RedInRen) and is currently coordinating the RICORS40 network.

Expert in hereditary kidney diseases

Currently, there are more than 300 hereditary kidney diseases. Among them, autosomal dominant polycystic kidney disease stands out, which was the topic of her doctoral thesis titled “Clinical, Genetic, and Molecular Studies of Autosomal Dominant Polycystic Kidney Disease.” This condition affects approximately one person per thousand and is considered the most common within this group. Additionally, there are many other hereditary kidney diseases, some of which are very rare and, therefore, difficult to diagnose. In this regard, Dr. Torra clarifies that “the diagnosis of these diseases presents significant challenges since early clinical suspicion and early diagnosis can make a big difference in the lives of these individuals.” However, she points out future challenges such as “the incorporation of artificial intelligence (AI), a tool that will open up many possibilities for both research and diagnosis of these conditions.”

Mandate objective

Chronic kidney disease Chronic kidney disease is underdiagnosed and is a cause of high morbidity and mortality, as well as high healthcare expenditure, resulting in a significant economic and social impact. It is estimated that this condition will be the fifth leading cause of death by 2040, making it urgent to implement preventive measures to reverse this trend. Among the main objectives of Dr. Torra’s tenure at the helm of ERA is to “promote excellence in renal medical care through education and research.”

From her perspective, nephrology will have to adapt due to the increasing incidence of chronic kidney disease in the coming years. “We must decisively respond to changing contexts and cultivate relationships with other institutions to generate synergies and share data, but the health of the patient will be my number one priority as a physician and one that I will always keep in mind, especially as President of ERA.”

First female presidency

Dr. Torra is the first woman to hold the presidency of this scientific society, which she considers an honor and, at the same time, a great challenge. “I face it with a lot of humility but even more determination. I embark on this new responsibility with great enthusiasm, extensive experience, and, most importantly, a current personal and professional life that allows me to devote time to my duties as President of ERA to enhance the prestige and role of ERA in international nephrology.”

The specialist acknowledges identifying with the “impostor syndrome” since many women of her generation have faced serious difficulties in balancing their professional and family lives, contributing to a prominent male presence. “Sometimes it is even difficult for me to recognize the fact of identifying with the impostor syndrome because that implies accepting that I really have the capabilities for it.”

For her, it is a pride to break this barrier and pave the way for other nephrology specialists so that they can aspire to occupy positions of responsibility and represent nephrologists in different international institutions.

Other biographical details of interest

Dr. Torra studied Medicine and Surgery at the Autonomous University of Barcelona (UAB) and specialized in Nephrology at the Clínic Hospital. Subsequently, she delved into the field of genetics under the guidance of Dr. Xavier Estivill and specialized in the study of hereditary kidney diseases, on which she has published more than 200 articles and has developed various projects and received competitive grants (ISCIII, Marató TV3…). She has twice received the “Iñigo Álvarez de Toledo” Nephrology Research Award, one of the most prestigious in Spain.

La música és poderosa. Pot tenir tal efecte sobre el nostre estat d’ànim que una persona pot passar de la tristesa a l’alegria quasi de manera instantània. Però a més, pot ajudar a millorar el nostre benestar i tenir efectes positius sobre el nostre estat físic i millorar aspectes com la percepció del dolor.

Quan l’activitat musical ve proposada i dissenyada per part d’un musicoterapeuta professional aquests efectes es potencien encara més. Així ho han explicat Iria González, investigadora principal, infermera i responsable de projectes d’humanització hospitalària a l’IIB Sant Pau, i Patricia Martí, psicooncòloga i musicoterapeuta, Oncolliga i ESMUC, que van presentar els resultats del projecte de musicoteràpia en pacients de càncer hematològic al Sónar+D.

Les expertes han explicat que la musicoteràpia és aquella disciplina que utilitza aquesta capacitat de la música per millorar el benestar d’una persona. S’utilitza en molts àmbits, i en concret, des de l’IIB Sant Pau estudiem quins són els efectes de la musicoteràpia en pacients amb càncers hematològics i els seus cuidadors. Els resultats de la investigació han demostrat una reducció de la tristesa, ansietat i del malestar físic en els pacients.

Aquest projecte de recerca neix d’una col·laboració amb l’Institut de Recerca de Sant Pau, l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, l’Escola Superior de Música de Catalunya (ESMUC) i Oncolliga i  està adreçat tant a les persones afectades de malaltia onco-hematològica que es trobin ingressades a la unitat, ja sigui a una càmera d’aïllament com a una habitació, como els seus cuidadors familiars i els professionals sanitaris de la unitat.

El Sónar+D és un espai dedicat a veure, escoltar, tocar i debatre sobre com s’aplica la IA a la producció musical o audiovisual, a abordar les possibles conseqüències ètiques, industrials i socials del seu ús.

El Dr. Saül Martínez-Horta, investigador del grup de Malaltia del Parkinson i Trastorns del Moviment a l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau i neuropsicòleg de la Unitat de Trastorns del Moviment del Servei de Neurologia del mateix hospital, ha estat guardonat amb el premi extraordinari de l’Escola de Doctorat del Departament de Medicina de la Universitat Autònoma de Barcelona (UAB) per la tesi defensada el curs 2020/21. Dirigida pel Dr. Jaume Kulisevsky i el Dr. Javier Pagonabarraga, porta per títol “Correlats neuronals i neuropsicològics de les alteracions cognitives i conductuals en les fases prodròmica i inicial de la malaltia de Huntington”. Podeu llegir-la aquí.

Els objectius de la tesi s’han adreçat a la recerca d’algunes respostes per a incògnites encara pendents al voltant de la malaltia de Huntington, una patologia neurodegenerativa i minoritària de base genètica.

D’aquesta manera, al llarg de les cinc publicacions científiques que componen la tesi, s’han estudiat quins mecanismes modulen l’inici de la malaltia i el dany cerebral associat en persones que tenen una mateixa carrega genètica, demostrant l’efecte del bilingüisme sobre aquests factors. Igualment, s’han identificat marcadors subtils de dany neuronal en persones asimptomàtiques demostrant alhora que presenten certes anomalies visuoperceptives prèviament mai descrites. També s’han identificat els mecanismes neuronals implicats en el desenvolupament i en la severitat de la irritabilitat i agressivitat en els pacients afectats, el perfil de deteriorament cognitiu que acompanya la transició a la demència i els canvis cerebrals que associen els pacients amb patrons de deteriorament cognitiu més severs.

Segons el Dr. Martínez-Horta, “el caràcter minoritari de la malaltia de Huntington ha suposat, comparat amb altres processos neurodegeneratius més freqüents, un avenç desajustat i lent en la comprensió dels mecanismes neuropatològics responsables de les complexes manifestacions clíniques que suposa la malaltia, així com en la identificació i descripció detallada dels fenotips clínics que la caracteritzen”.

També emfatitza en com “el desenvolupament d’estudis observacionals multicèntrics i internacionals ha permès, en els últims 15 anys, aprofundir de manera molt notable en el coneixement de la malaltia gràcies al seguiment de grans cohorts de persones afectades, feina que a la Unitat de Trastorns del Moviment i, específicament a la Unitat Funcional de malalties minoritàries que cursen amb trastorns del moviment, anem realitzant des de fa més de 12 anys havent situat l’Hospital de Sant Pau com a un dels centres més reconeguts en l’àmbit internacional en l’abordatge i investigació de la malaltia de Huntington”.

Actualment, el Dr. Martínez-Horta juntament amb la resta de membres que formen part de la Unitat dedicada al tractament i recerca en malaltia de Huntington, realitzen assajos clínics pioners i treballen a identificar mecanismes biològics que de manera addicional a la mutació genètica que causa la malaltia, juguin un paper central en el curs clínic i puguin suposar noves dianes terapèutiques.

Fa 15 anys, una dona a la trentena va ser diagnosticada de càncer de ronyó metastàtic. L’oncòleg Jose Pablo Maroto, de l’Hospital Santa Creu i Sant Pau – IIB Sant Pau, a Barcelona, va decidir tractar-la amb el fàrmac temsirolimus, que va funcionar molt millor del que s’esperava. La pacient va superar el càncer. Nou anys després se li va detectar una metàstasi en os, però també aquesta vegada el temsirolimus va resultar efectiu.

Ara, gràcies a la generositat i la tenacitat d’aquesta pacient, i a la col·laboració entre el seu oncòleg i els investigadors del Centre Nacional d’Investigacions Oncològiques (CNIO), s’ha descobert per què el temsirolimus ha estat tan efectiu en aquest cas i en els altres dos pacients.

És una troballa que permetrà identificar altres malalts amb càncer de ronyó per als qui el temsirolimus i altres fàrmacs de la mateixa família seran, amb gran probabilitat, el tractament idoni. Avui dia aquests fàrmacs -inhibidors de la via de mTOR- es fan servir només quan fallen altres.

“Actualment els fàrmacs de la família del temsirolimus no solen ser la primera opció en càncer de ronyó, però aquest resultat indica que en alguns pacients, molt específics, sí que ho han de ser, perquè funcionen molt bé. Ara sabem com identificar aquests pacients”, diu Cristina Rodríguez-Antona, investigadora del programa de Genètica del Càncer Humà del CNIO.

Finançat per carreres solidàries

Rodríguez-Antona, Maroto i altres investigadors i oncòlegs del CNIO i de l’Institut de Recerca de l’Hospital de Sant Pau publiquen ara aquest resultat a la revista International Journal of Cancer, en un treball del qual és primer autor Juan María Roldán-Romero.

La investigació ha estat finançada en part amb donacions obtingudes en carreres solidàries organitzades pel Club d’Atletisme A 4 al KM, de les Franqueses del Vallès (Barcelona), promogudes per la pacient.

“Aquesta publicació és un orgull”, diu Maroto. “És una col·laboració entre una associació que organitza any rere any una carrera popular per a la investigació en càncer renal; pacients que cedeixen mostres en moments difícils; i investigadors bàsics i clínics. Tot, per respondre a per què ha funcionat tan bé aquest tractament? No és el primer cas en què ens plantegem aquesta pregunta, però sí dels primers en què obtenim una resposta clara”.

Trobar aquesta resposta ha estat anys. Va caldre trobar més casos similars als de la primera pacient. L’equip del Sant Pau els va anar seleccionant i enviant les mostres al CNIO, on van ser analitzades en profunditat.

Mutacions en una proteïna implicada a l’autofàgia

La clau està en unes mutacions molt poc freqüents a la proteïna USP9X, que regula processos cel·lulars crítics per al creixement dels tumors. La investigació de Roldán-Romero mostra que les mutacions anul·len la funció de USP9X, i quan això passa la cèl·lula no recicla bé les seves deixalles i mor. El temsirolimus actua sobre una via molecular diferent, però té un efecte semblant; als pacients en què no funciona USP9X, l’impacte d’aquest fàrmac es potencia.

Ho explica Rodríguez-Antona: “Per entendre l’efecte de les mutacions a USP9X vam desenvolupar models cel·lulars i vam fer assajos proteòmics que van indicar que les cèl·lules tumorals sense USP9X tenien una alteració a l’autofàgia cel·lular [el procés pel qual la cèl·lula recicla els seus productes de deixalla]. El temsirolimus també altera l’autofàgia, cosa que causa un efecte sinèrgic, fent que els tumors responguin millor a aquest tractament”.

Una nova diana terapèutica

A més de per identificar altres pacients amb mutacions a USP9X, que podrien beneficiar-se del tractament amb fàrmacs de la família del temsirolimus, aquesta troballa recolza el desenvolupament de nous fàrmacs inhibidors d’UPS9X com a estratègia terapèutica innovadora.

“Un compost que anul·lés la funció d’UPS9X tindria un efecte sinèrgic amb el temsirolimus, augmentant la seva eficàcia antitumoral”, assenyala Rodríguez-Antona.

Els autors de l’estudi llancen un missatge últim: “Els estudis translacionals són complexos perquè requereixen una estreta col·laboració entre clínics i investigadors bàsics. A més, els pacients tenen un paper principal donant les seves mostres en un moment molt difícil. Aquest estudi en tumors poc freqüents només s’ha pogut dur a terme gràcies a la generositat dels pacients, les mostres dels quals són la base de tot el treball molecular posterior i que van impulsar l’estudi des del començament”.

Article de referència

Roldán-Romer JM, Valdivia C, Sants M, Llanets J, Maroto P, Anguera G, Calsina B, Martinez-Monts A, Monteagudo M, Mellid S, Leandro-García LJ, Montero-Comte C, Cascó A, Roncador G, Coloma J, Robledo M, Rodriguez-Antona C. Deubiquitines USP9X els sensibles renal cancer cells to mTOR inhibition. Int J Cancer. 2023 Jun 1. doi: 10.1002/ijc.34575.

Research involving pregnant women, children, and infants represents a significant challenge for science, as safety requirements and study criteria are particularly strict. This often translates into an obstacle to obtaining new evidence-based results that allow for advancements and provide solutions to improve clinical practice in these population groups.

Although these cooperation networks have existed for several years, this situation can take a significant leap forward thanks to the renewal and innovation that this new network brings. Eighteen Spanish entities have signed a framework agreement within the Maternal and Child Health and Development Network (SAMID) of the Health Research Cooperative Networks for Health Outcomes (RICORS) program, coordinated by Dr. Elisa Llurba, the principal investigator of the Perinatal and Women’s Medicine Group at the Research Institute of the Hospital de Santa Creu i Sant Pau – IIB Sant Pau, director of the Obstetrics and Gynecology Department at the same hospital, and professor at the Autonomous University of Barcelona (UAB).

This RICORS-SAMID maternal and child consortium, established in 2008 and renewed in 2021 with the support of the Carlos III Health Institute of the Ministry of Health, consists of a total of 20 research groups and 27 associated clinical groups from different Spanish research institutes and healthcare centers. This means the participation of more than 300 researchers, including neonatology/pediatrics and obstetrics specialists, primary care pediatricians, biologists, anthropologists, specialists in perinatal mental health, midwives, nurses, primary care and NICU nurses, nutritionists, educators, graphic designers, physical education professionals, among others, who join forces to promote a comprehensive and collaborative plan to improve the health of women, mothers, and babies.

With this new framework agreement, the centers that are part of the RICORS-SAMID network will share research objectives and projects, as well as clinical data, images, and samples, allowing for the creation of the largest information bank in Spain. This will facilitate large-scale clinical trials, innovative studies such as big data and artificial intelligence, and contribute to leadership in this field at the European level.

According to Dr. Llurba, “the agreement signed within the RICORS-SAMID Network is a decisive step in promoting research through collaborative work in the field of maternal and child health, which will also attract talent and access competitive public and private funding.”

The coordinator of the RICORS-SAMID network explains that with this agreement, “we have achieved a legal framework that not only aims to facilitate research among different groups but also intends to be a tool to disseminate advancements so that users themselves and society, in general, can play a more active role in the process. For this reason, an open mailbox has been set up where citizens can express their needs and get involved in the research process through a co-creation and idea incubation process.”

IMPACTFUL PROJECTS

One example of the projects being developed within the RICORS-SAMID network is a study evaluating neurological development in newborns affected by congenital heart disease. Samples from both mothers and infants, as well as prenatal resonance and ultrasound images, and follow-up data during the first years of life, are being analyzed. The goal is to find neonatal and postnatal predictors associated with neurological development and the quality of life of these children.

“Congenital heart diseases are a relatively rare type of congenital malformation, but their impact on health is significant, and we need a lot of data that can be translated into clinical responses and truly improve the health of these children in their daily lives,” says Dr. Llurba.

Furthermore, other projects are underway, studying, for example, prognostic and diagnostic markers for preeclampsia and prematurity, intrauterine growth restriction and its long-term consequences, the effects of environmental pollution and prenatal exposure to substance abuse on maternal and child health, early reproductive losses and their impact on mental health, renal impairment in mothers with preeclampsia, improving the diagnosis of early gestational diabetes during the first trimester of pregnancy and its effect on child neurodevelopment, nutrition and its effects on childhood obesity, neonatal circulatory failure biomarkers, treatment of bacterial sepsis in newborns, resuscitation of premature infants, treatment of complications of neonatal hypoxic-ischemic encephalopathy, hypoxic-ischemic brain injuries, diabetes, and the experiences, needs, and expectations of families and patients. Additionally, projects focusing on health education, promoting healthy habits at any age, preventing sudden death and the sequelae of cardiorespiratory arrest through training actions aimed at professionals and citizens, as well as research on clinical and ethical aspects of pediatric palliative care, are also being developed within the network.

The hospitals and research institutes participating in the framework agreement are:

• Instituto de Investigación del Hospital de la Santa Creu i Sant Pau – IIB Sant Pau
• Instituto de Investigación Biosanitaria (IMIB) – Fundación para la Formación e Investigación Sanitarias de la Región de Murcia (FFIS)
• Instituto de Investigación Sanitaria La Fe – Fundación para la Investigación del Hospital Universitario La Fe de la Comunidad Valenciana
• Instituto de Investigación Hospital 12 de Octubre – Fundación Investigación Biomédica Hospital Universitario 12 de Octubre
• Instituto de Investigación Sant Joan de Déu (IRSJD) – Fundación Privada per a la Recerca i la Docència Sant Joan de Déu
• Instituto Biocruces Bizkaia – Asociación Instituto de Investigación Sanitaria Biocruces Bizkaia
• Grupo de Investigación AFIN – Universitat Autònoma de Barcelona – UAB
• Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) – Fundación para la Investigación Biomédica del Hospital Universitario La Paz
• Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) – Fundació de Recerca Clínic Barcelona
• Instituto de Investigación Sanitaria Gregorio Marañón – Fundación para la Investigación Biomédica del Hospital Gregorio Marañón
• Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA) – Fundación Pública Andaluza para la Investigación Biosanitaria de Andalucía Oriental – Alejandro Otero
• Instituto de Investigación Sanitaria Aragón – Fundación Instituto De Investigación Sanitaria Aragón
• Instituto de Investigación Sanitaria Hospital Clínico San Carlos – Fundación para la Investigación Biomédica del Hospital Clínico San Carlos
• Instituto de Investigación Sanitaria Valdecilla (IDIVAL) – Fundación Instituto de Investigación Marqués de Valdecilla
• Instituto de Investigación Sanitaria de Santiago de Compostela – Fundación Instituto de Investigación Sanitaria de Santiago de Compostela
• Fundació Puigvert
• Instituto de Investigación Sanitaria del Principado de Asturias – Fundación para la Investigación y la Innovación Biosanitaria del Principado de Asturias

The phase I clinical trials unit of the Medicines Research Center (CIM) of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has renewed the Certificate of compliance with the rules of good clinical practice (BPC) after having passed the inspection by the Direcció General d’Ordenació i Regulació Sanitària of the Generalitat de Catalunya.

This certificate recognizes compliance with the requirements necessary to carry out phase I clinical trials or first administration of medicines in humans, in accordance with the principles of good clinical practice (GCP) in force in the European Union and the technical and sanitary requirements of the phase I units published by the Department of Health of the Generalitat de Catalunya.

The CIM carries out phase I efficacy and tolerability clinical trials, pharmacokinetics, drug metabolism and interaction studies, bioequivalence studies and first studies in humans.

La participació de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau a la Festa de la Ciència enguany va ser tot un èxit. Durant aquest esdeveniment, que s’ha consolidat com una trobada pública anual amb la ciència i la recerca a la nostra ciutat, molta gent ens va venir a veure i es va divertir amb les activitats de divulgació científica, jocs, micro xerrades i tallers que l’IIB Sant Pau va preparar.

Centenars de petits i grans van col·laborar per fer el nostre trencaclosques científic gegant. A més, la periodista Cristina Junyent va fer una entrevista per a Ràdio Farró amb la Dra. Elena Roselló-Díez, investigadora del Grup de Recerca Associat IIB Sant Pau en Cirurgia Cardíaca i especialista en Cirurgia Cardíaca a l’Hospital de Sant Pau que va parlar sobre la innovació tecnològica en cirurgia cardíaca.

La Dra. Roselló-Díez també va liderar el taller “Descobreix com funciona el cor i l’aparell circulatori”, en el qual va explicar els components de l’aparell cardiovascular i les seves funcions amb diferents objectes i l’ajuda de material gràfic on els participants van poder reconstruir una maqueta del nostre sistema cardiovascular i aprendre com funciona.

A més, es van dur a terme diverses microxerrades, una d’elles a càrrec de l’Ana Novoa, investigadora de l’IIB Sant Pau al Departament ASPB Servei de Sistemes d’Informació en Salut (SeSIS) de l’Agència de Salut Pública de Barcelona (ASPB) amb el títol “Viure juntes per viure millor: habitatge cooperatiu i salut”. El Dr. Robert Belvís i la Dra. Noemi Morellón, professionals de l’IIB Sant Pau i de l’Hospital de Sant Pau van parlar sobre “Elèctrodes al cervell per combatre el mal de cap multiresistent” i el Dr. Israel Fernández-Cadenas, investigador principal del Grup de Farmacogenòmica i Genètica Neurovascular de l’IIB Sant Pau va oferir la microxerrada: “Com la genètica ens ajuda a trobar nous tractaments per a malalties molt comunes”.

The Inter-American Society of Cardiology has awarded the Academic and Scientific Career Award to Prof. Lina Badimon, Director of the Cardiovascular Disease Research Area and the Molecular Pathology and Therapeutics Research Group of Atherothrombotic and Ischemic Diseases at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau.

This award, which represents recognition from the international scientific community for the work of this outstanding researcher, was presented during the annual congress of this scientific society, which is currently taking place in Panama.

Prof. Badimon expressed her gratitude for this distinction and commented that one of the achievements in her career that she is most satisfied with are “the original research papers carried out over the years that are leading to the transfer of knowledge to clinical practice for the benefit of patients.”

Furthermore, among her tasks, she highlights the training of research personnel as one of the most satisfying aspects, as well as the collaborative work with groups “from other countries and continents who are also developing their own research programs and projects.”

Prof. Lina Badimon views the future of cardiology research with optimism. “I believe we will have a period of great value in the coming years thanks to the incorporation of new technologies that facilitate molecular and genetic studies, allowing knowledge to be increasingly applied in clinical practice.”

Finally, Prof. Badimon commented that scientific activity “requires sustained dedication, often in silence, and in many cases, it is not widely recognized. That is why awards like the one I am receiving now are very gratifying.”

Núñez C, García-Alix A, Arca G, Agut T, Carreras N, Portella MJ, Stephan-Otto C. Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study. J Child Psychol Psychiatry. 2023 Mar 22. doi: 10.1111/jcpp.13790. Epub ahead of print. PMID: 36946606.

Dr. Margarita Majem Tarruella, a researcher from the Clinical Oncology Group at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, and an oncologist at the same hospital, has participated in two studies that have been published in the prestigious journal The New England Journal of Medicine and presented at the American Society of Clinical Oncology (ASCO) conference currently taking place in Chicago, United States.

On one hand, the results of the ADAURA clinical trial have revealed that adjuvant therapy with osimertinib, an inhibitor of the epidermal growth factor receptor (EGFR), has significantly prolonged overall survival in patients with early-stage non-small cell lung cancer with EGFR gene mutations.

The randomized, double-blind, phase III clinical trial analyzed data from 682 patients, of whom 339 received osimertinib and 343 received a placebo. Among patients with stage II to IIIA disease, the overall 5-year survival rate was 85% in the osimertinib group and 73% in the placebo group.

According to these data, adjuvant therapy with osimertinib has demonstrated a significant benefit in overall survival among patients with non-small cell lung cancer with EGFR gene mutations.

These results offer new hope for patients in the early stages of the disease, as they represent the largest reduction in mortality ever recorded in the field of lung cancer and highlight how targeted therapies against tumor alterations are driving oncology towards more effective treatments for specific groups of patients.

EGFR alterations are the most common type of mutation in lung tumors in non-smokers, while they are not as frequent in people who have smoked, as detailed by Dr. Majem.

“This is the first time we have seen such a magnitude of improvement in lung cancer survival, and we believe it is a very hopeful outcome that will translate into an improved prognosis for these patients.”

Combination of immunotherapy before and after surgery

On the other hand, another study in which Dr. Majem participated concluded that patients with early-stage non-small cell lung cancer who are candidates for surgery and receive neoadjuvant treatment with pembrolizumab in combination with chemotherapy followed by surgical resection and adjuvant treatment with pembrolizumab show a better therapeutic response and longer progression-free survival compared to conventional treatment, which consists of neoadjuvant chemotherapy followed by surgery.

This is a randomized, double-blind clinical trial called KEYNOTE-671, which analyzed follow-up data from 797 patients over 25.2 months. The results showed that the 24-month progression-free survival rate was 62.4% in the pembrolizumab-treated group compared to 40.6% in the placebo group. Additionally, a greater pathological response was observed in 30.2% of participants in the pembrolizumab group compared to 11.0% in the placebo group.

According to Dr. Majem, “these results provide a new perspective on the treatment of early-stage lung cancer and could have a significant impact on how this disease is approached in the future.”

Reference articles

• Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohé C, Wang J, Goldman JW, Lu S, El seu WC, de Marinis F, Shepherd FA, Lee KH, NT, Dechaphunkul A, Kowalski D, Poole L, Bolanos A, Rukazenkov I, Wu YL; ADAURA Investigators. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med. 2023 Jun 4. doi: 10.1056/NEJMoa2304594. Epub ahead of print. PMID: 37272535.
• Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodríguez-Abreu D, Chaft JE, Novell S, Yang J , Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab per Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Jun 3. doi: 10.1056/NEJMoa2302983. Epub ahead of print. PMID: 37272513.

Els resultats d’un estudi, liderat per Maria Galán Arroyo, investigadora de l’Institut de Recerca de l’Hospital de Santa Creu i Sant Pau (IIB Sant Pau) i de la Universitat Rey Juan Carlos (URJC), i Cristina Rodríguez, investigadora de l’IIB Sant Pau, mostren que l’acció d’una molècula (el pèptid SS-31) sobre els mitocondris cel·lulars disminueix la incidència i la mortalitat d’aquesta malaltia.

El pèptid SS-31 dirigit al mitocondri té la capacitat de limitar el remodelat vascular que condueix al desenvolupament de l’aneurisma d’aorta abdominal (AAA). Aquesta és la principal conclusió de l’estudi publicat a la revista científica British Journal of Pharmacology.

L’AAA és una malaltia degenerativa que afecta el 6-9% dels homes més grans de 65 anys. És una condició en què l’aorta abdominal, l’artèria principal que subministra sang a l’abdomen i les cames, es dilata i es debilita. A mesura que l’aneurisma creix, augmenta el risc que es trenqui, cosa que pot causar una hemorràgia interna potencialment mortal.

“Fins ara, no hi ha un tractament farmacològic eficaç per a l’aneurisma d’aorta abdominal. Tot i això, aquest treball revela una nova estratègia terapèutica per al tractament d’aquesta malaltia”, explica Cristina Rodríguez, una de les investigadores que ha liderat l’estudi.

Els resultats mostren que el tractament amb el pèptid SS-31 limita la disfunció mitocondrial, l’estrès de reticle endoplàsmic (que suposa una alteració a la síntesi de proteïnes i condueix a la producció de proteïnes defectuoses) i l’estrès oxidatiu vascular en un model experimental de la malaltia. “Això resulta en una disminució de la incidència i gravetat de l’AAA, una reducció del diàmetre aòrtic i de la mortalitat, així com una millora en múltiples processos associats al desenvolupament de l’aneurisma, com una inflamació menor i millora de la integritat de la matriu extracel·lular”, afegeix María Galán Arroyo, coautora de l’estudi i investigadora de la URJC i de l’IIB Sant Pau.

Estudis clínics previs també han demostrat l’eficàcia del SS-31 en el tractament d’altres malalties. Per exemple, s’ha demostrat que el pèptid SS-31 és efectiu en la reducció del dany cerebral després d’un accident cerebrovascular i la millora de la funció cardíaca en pacients amb insuficiència cardíaca.

Aquest nou treball suggereix que la SS-31 podria ser una estratègia terapèutica interessant per al tractament de l’AAA. “Els nostres resultats representen un important avenç en la investigació sobre el tractament de l’aneurisme d’aorta abdominal i ens acosta un pas més a trobar una cura efectiva per a aquesta malaltia”, subratlla la Dra. Galán.

L’estudi ha estat liderat per Maria Galán i Cristina Rodríguez, investigadores de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau (IIB Sant Pau), del grup de l’Àrea de Malalties Cardiovasculars (CIBERCV), dirigit per José Martínez González ( Institut d’Investigacions Biomèdiques de Barcelona (CSIC) amb la col·laboració d’un equip de l’Àrea CIBER de Diabetis i Malalties Metabòliques Associades (CIBERDEM) i de la Universitat Autònoma de Barcelona.

Article de referència

Navas-Madroñal, M., Almendra-Pegueros, R., Puertas-Umbert, L., Jiménez-Altayó, F., Julve, J., Pérez, B., Consegal-Pérez, M., Kassan, M., Martínez-González, J., Rodriguez, C., & Galán, M. (2023). Targeting mitochondrial stress with Szeto-Schiller 31 prevents experimental abdominal aortic aneurysm: Crosstalk with endoplasmic reticulum stress. British Journal of Pharmacology, 1– 20. https://doi.org/10.1111/bph.16077

The executive committee of the Spanish Society of Psychiatry and Mental Health (SEPSM) has appointed Dr. Justo Pinzón Espinosa, a researcher at the Mental Health Group of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, and a psychiatrist at the same hospital, as one of the two coordinators of the recently created Young Psychiatrists Working Group. In this new section, he will represent and advocate for the interests of psychiatrists up to the age of 35 and will serve as a link between this group and the rest of the scientific society.

“For me, this appointment is a logical and natural step after my tenure as president of the Spanish Society of Psychiatry Residents in 2019 and 2020,” says Dr. Pinzón, who explains that “during this period, we developed strategies, with the board of directors, to promote research, teaching, and the improvement of the quality of care for psychiatry residents in Spain. I also strengthened the presence and participation of Spanish residents in the European Federation of Psychiatry Residents, where I served as national coordinator of residents’ associations and leader of the ‘Psychiatry Across Borders’ working group until 2021.”

Among the main objectives of the new Young Psychiatrists section of the SEPSM, Dr. Pinzón highlights that “the first step will be to establish the functional and organizational foundations, as well as to establish formal collaborations and strengthen ties with the young sections of other psychiatric societies in Europe, such as the European College of Neuropsychopharmacology, the European Psychiatric Association, or the Royal College of Psychiatrists, and internationally with institutions such as the American Psychiatric Association or the World Psychiatric Association.” Additionally, they aim to “promote spaces for the exchange of ideas and socialization during important events in the field of Spanish Psychiatry to foster collaborations throughout the country.”

Women and older patients with atypical presentations of ST-segment elevation myocardial infarction (STEMI) experience greater delays in diagnosis and treatment activation in emergency departments, according to the results of a study led by Gemma Berga Congost from the Nursing Research Group at the Research Institute of Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and a nurse at the same hospital.

The study, which included 330 patients with STEMI admitted to the Emergency Department of Hospital de Sant Pau, revealed that age over 65 and presentation of the first medical contact outside the Emergency Department were associated with an increase in treatment activation time. In addition, women over 65 showed the longest activation time. The results highlight the need to develop strategies to reduce the time to initiate treatment in these specific patient groups.

ST-segment elevation myocardial infarction is more common in men than in women, and the average age of patients admitted for myocardial infarction in Spain is around 65 years. “In contrast, the average age of women is 10 years older than that of men, probably due to the protective effect of estrogen,” emphasizes this expert.

The delay in diagnosis experienced by these groups “may be attributable to the atypical symptoms they most frequently present. Therefore, in addition to typical symptoms, other manifestations identified in our registry should be considered in order to establish an early diagnosis.”

It is also important to note that both women and the elderly have a lower perception of risk, which delays the request for medical assistance, resulting in delayed diagnosis and treatment.

The study from IIB Sant Pau has also identified that age over 65 is a predictor of delay in diagnosis and provides new data regarding the age and gender gap. As Berga points out, “there is no positive association between gender and age in patients under 65. However, if the age is over 65, it is observed that women have a longer emergency-activation time than men.”

These findings underline the importance of addressing the specific needs of these patient groups to improve activation time. Developing targeted strategies to accelerate activation time in these subgroups is crucial to improve the quality of care provided in the Emergency Department.

Reference article

Gemma Berga Congost, Maria Antonia Martinez Momblan, Jonatan Valverde Bernal, Adrián Márquez López, Judit Ruiz Gabalda, Joan Garcia-Picart, Mireia Puig Campmany, Salvatore Brugaletta. Association of sex and age and delay predictors on the time of primary angioplasty activation for myocardial infarction patients in an emergency department. Heart & Lung (2023). https://doi.org/10.1016/j.hrtlng.2022.10.014

En el marc de la 24a Jornada de Nefrologia i Atenció Primària, organitzada per la Unitat d’Hipertensió i Prevenció de Mal Renal de la Fundació Puigvert – IIB Sant Pau, s’ha posat de manifest la necessitat d’una atenció coordinada i multidisciplinària a les gestants que presenten HTA perquè pot estar associada a una malaltia renal i ser un factor predictiu de sofrir preeclàmpsia. A més, confirmen les expertes, les dones que hagin sofert una complicació obstètrica com la preeclàmpsia tindran un risc alt de desenvolupar una malaltia cardiovascular com HTA, diabetis, obesitat i tromboembolisme, entre altres patologies.

La preeclàmpsia és una malaltia específica de l’embaràs i d’afectació multisistèmica (sobretot, ronyó, fetge i cervell), definida com una hipertensió que apareix a partir de les 20 setmanes de gestació. Actualment, és necessari realitzar proves de detecció a totes les embarassades i el garbellat del primer trimestre de la preeclàmpsia prematura s’inclou en el Protocol de Seguiment de l’Embaràs a Catalunya des de 2018.

La Dra. Elisa Llurba, directora del Servei de Ginecologia i Obstetrícia de l’Hospital de Sant Pau i Cap del Grup de Medicina Perinatal i de la Dona de l’Institut de Recerca de l’Hospital de Sant Pau – IIB Sant Pau, ha afirmat que “a l’Hospital de Sant Pau disposem d’un Programa de Garbellat de Preeclàmpsia que es realitza amb criteris d’història clínica materna (per exemple, haver-la sofert anteriorment), més la pressió arterial alta i l’avaluació del flux en les artèries uterines. Aquest garbellat és capaç d’identificar a un 65-70% de les dones que desenvoluparan preeclàmpsia preterme”.

Embaràs, HTA i malaltia renal

Un dels casos més comuns de la consulta de nefrologia de la Fundació Puigvert és la de dones amb poliquistosis renal autosòmica dominant (PQRAD), la malaltia renal hereditària més freqüent, quan es plantegen el desig gestacional. Es tracta d’una malaltia congènita que es diagnostica a través d’antecedents familiars de primer grau i es descarta mitjançant una ecografia. La Dra. Patrícia Fernández-Llama, cap de la Unitat d’Hipertensió Arterial del Servei de Nefrologia de la Fundació Puigvert, afirma que “les dones amb malalties renals tenen més risc de complicacions greus tant per a elles com per al futur nadó. És per aquest motiu que obstetres i nefròlogues de l’Hospital Sant Pau i la Fundació Puigvert, respectivament, treballem, coordinadament en una consulta multidisciplinària per a abordar aquests embarassos d’alt risc: si es planifica l’embaràs amb la malaltia renal estabilitzada, el risc de complicacions es redueix perquè ens permet anticipar-nos i aplicar estratègies d’intervenció precoces per a minimitzar els riscos.”

Preeclàmpsia, avantsala d’una malaltia cardiovascular

Un estudi retrospectiu de l’Institut Català de la Salut (ICS) a la ciutat de Barcelona ha registrat un total de 1976 episodis de preeclàmpsia en 1329 dones (algunes van tenir dos o més episodis) en els últims vint anys. L’anàlisi i seguiment d’aquestes pacients durant aquest període posa de manifest que les dones que han sofert un o més episodis de preeclàmpsia desenvolupen al cap dels anys alguna malaltia cardiovascular greu com HTA, diabetis, obesitat, esdeveniments cardiovasculars i fins i tot malaltia renal, amb molta més freqüència que les dones que mai van presentar preeclàmpsia.

La conclusió continua sent la mateixa: una bona comunicació i coordinació entre pacients, mèdics/as de família, obstetres i nefròlegs/as per a la detecció, control i seguiment de les dones en edat reproductiva amb HTA i desig gestacional és vital per a prevenir la preeclàmpsia i la seva morbimortalitat associada.

The Cellular Cultures Platform of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, coordinated by Estefanía Segalés, is a service that offers different facilities where you can work with both primary cultures obtained from human tissues and experimental animal cultures, as well as continuous cell lines and Genetically Modified Organisms (GMOs) of levels I and II.

Users have the necessary basic equipment to obtain and maintain cell cultures: 25 laminar flow hoods and biological safety cabinets, 28 CO2 incubators, ovens, centrifuges, water baths, inverted microscopes, balances, vacuum traps, cell counters, refrigerators, freezers (-20 and -80°C), hybridization ovens, and autoclaves.

As a user of this platform, Dr. Alba Tristán Noguero, a postdoctoral researcher in the Molecular Pathophysiology of Synaptic Plasticity Group at IIB Sant Pau, explains that they mainly use it to maintain primary mouse neuron cultures and human neurons in co-culture with murine astrocytes.

“The infrastructure of the Cellular Cultures Service has helped us in the project of the Molecular Physiology of Synaptic Plasticity laboratory, allowing the study of SYNGAP1-related developmental epileptic encephalopathy. With the establishment and maintenance of these human and murine cultures, we have been able to better understand the pathophysiology of the disease and test different treatments.”

What Dr. Tristán apreciates the most about the Cellular Cultures Platform is “the perfect organization and management, as well as the availability to answer questions and adapt to the users’ needs.”

On the other hand, David Santos, a researcher in the group studying diseases characterized by lipid alterations, explains that he spends at least one-third of his working day in the Cellular Cultures Platform. “Most of the experimental work I do depends on cell cultures, from cellular metabolism studies to the injection of labeled foam cells with isotopes into animal models of experimentation.”

For him, this service is indispensable, “without this platform, it would be impossible for me to carry out these experiments. On the other hand, having this platform has allowed me to carry out important collaborations with other research groups, both nationally and internationally.”

This researcher highlights that reliability is one of the aspects he values the most about this platform. “Knowing that I leave my cultures in a secure area where regulations are met, both to protect the user and the cells, in terms of contamination control, equipment supervision and maintenance, PPE administration, among others, gives me peace of mind when performing my experiments and validating the results I obtain.”

A study co-led by researchers from the Neurobiology of Dementia group at the Research Institute of Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, published in the prestigious journal Neuron, of Cell group, describes that harmful proteins that accumulate in the brains of people with Alzheimer’s disease spread through synapses.

The research, led by Professor Tara Spires-Jones’ team at the UK Dementia Research Institute at the University of Edinburgh and carried out by IIB Sant Pau in collaboration with the Institute of Advanced Chemistry of Catalonia (IQAC) of the Spanish National Research Council (CSIC), provides new evidence that could be the key to stopping the progression of Alzheimer’s disease. The study was conducted under the European COEN project, funded by CIBERNED and coordinated by Dr. Alberto Lleó, a researcher in the Neurobiology of Dementia group at IIB Sant Pau and head of the Neurology department of the same hospital.

The accumulation of the Tau protein in neurons in the form of neurofibrillary tangles is one of the most characteristic aspects of Alzheimer’s disease. The deposits of this protein spread through brain circuits, disrupting communication between brain cells, leading to altered brain functions. It is the first time that these abnormal forms can be observed in human brains spreading through synapses.

Synapses are the points of connection between brain cells that allow chemical and electrical messages to flow, and this process is vital for normal brain function. Synapses are lost in Alzheimer’s disease, and the loss of these connections significantly predicts memory loss and other intellectual functions in these patients.

The research team examined over one million synapses from 42 individuals using innovative techniques with high-powered and super-resolution microscopes in collaboration with the IQAC-CSIC, which allowed them to visualize the flow of proteins within individual synapses. The researchers were able to observe that small deposits of the Tau protein, known as oligomers, were present on both sides of the synapses in individuals who died from Alzheimer’s. That is, both in the neuron that sends signals and in the one that receives them, indicating that synapses have the ability to transmit toxic Tau proteins from one part of the brain to another.

According to Dr. Sílvia Pujals, Ramón y Cajal researcher at IQAC-CSIC, “this study demonstrates how super-resolution microscopy, capable of visualizing nano-scale structures, has great potential in the study of the molecular mechanisms involved in diseases.”

These data reinforce the hypothesis that stopping the spread of the toxic form of the Tau protein in synapses may be a promising strategy for treating Alzheimer’s disease in the future, explains Dr. Lleó. “If we can block the passage of the most pathological form of the Tau protein, which are the oligomers, from one neuron to another, we could probably stop the progression of Alzheimer’s disease. Because we know that the progression of the disease is related to the expansion of the protein throughout the brain.”

The principal investigator, Professor Tara Spires-Jones from the UK Dementia Research Institute at the University of Edinburgh, indicates that “We have known for over 30 years that tangles spread through the brain during Alzheimer’s disease, but how they spread has remained a mystery. Wherever tangles appear in the brain, neuron death follows, contributing to the decline in cognitive ability. Stopping the spread of toxic tau is a promising strategy to stop the disease in its tracks.”

Dr. Sònia Sirisi Dolcet, postdoctoral researcher in the Neurobiology of Dementia group at the IIB Sant Pau, explains that Tau oligomers, which travel through synapses, “are a very early form in the aggregation process of this protein. That is, they are present in very early stages of Alzheimer’s disease.” Therefore, if strategies can be developed to prevent the spread of this protein throughout the brain in these early stages, its progression could be prevented or stopped.

Image: 3D reconstruction of super-resolution microscopy images, where it is seen that the Tau protein in its oligomeric form (in yellow) is located where there are pre-synapses (in magenta).

Reference Article  

Colom-Cadena et al., Synaptic oligomeric tau in Alzheimer’s disease — A potential culprit in the spread of tau pathology through the brain, Neuron (2023), https://doi.org/10.1016/j.neuron.2023.04.020