Scientific Report 2022-23. Cima Universidad de Navarra
CIMA UNIVERSIDAD DE NAVARRA
SCHOOLS OF MEDICINE, SCIENCES, NURSING, AND PHARMACY AND NUTRITION
About us, mission and purpose
Cima Universidad de Navarra is a biomedical institute of Universidad de Navarra committed to excellence in translational research based on novel biological knowledge and constant innovation in the development of new drugs and therapies.
In collaboration with Clínica Universidad de Navarra and other national and international institutions, it is committed to finding therapeutic solutions for real patient needs.
Cima has enjoyed the status of University Research Institute of the Universidad de Navarra since 2018. In this context, it shares its mission of service to patients and society through excellent work, freedom, respect, a multidisciplinary approach, responsibility, service and an international dimension.
Cima collaborates with professionals from Hospital Universitario de Navarra, Navarrabiomed and Universidad Pública de Navarra within the framework of the Healthcare Research Institute of Navarre (IdiSNA), which it helped establish and accredit.
CLÍNICA UNIVERSIDAD DE NAVARRA
Introduction
Since the beginning of the 2022-2023 academic year, I have enjoyed the inspiring responsibility of heading this extraordinary biomedical research center at the Universidad de Navarra.
My first words as General Director are to thank the Chair and Board of Trustees of FIMA (the organization that owns Cima Universidad de Navarra) for the trust they have placed in me. I would also like to give a special mention to all the professionals who have contributed to ensuring that Cima is true to its purpose: research to heal for the benefit of patients and society.
In its commitment to be an international reference center in biomedical research that favors innovation and the development of advanced therapies, Cima and its multidisciplinary teams have achieved important results, as shown in the more than 300 articles published in high-impact scientific journals.
This academic year marked the presentation of the Cancer Center Clínica Universidad de Navarra (CCUN) for education, research and care on the biomedical campus that now forms part of the scientific activity in solid and hematological tumors. These interdisciplinary groups, made up of professionals from Clínica Universidad de Navarra and Cima, are sure to promote a personalized approach for each patient.
Furthermore, the discoveries made in our laboratories have led to more than fifty R&D contracts and agreements with companies, as well as the implementation of strategic alliances with international reference centers, such as the Weizmann Institute of Science (Israel) and the University of Oxford (United Kingdom).
These results would not have been possible without the financial support of so many individuals and institutions, which share the belief that biomedical research can have a major impact on society. Moreover, these scientific advances are only possible thanks to the commitment and excellence of all Cima professionals, whose generosity prompts them to search tirelessly for new therapies. To all of them, thank you very much.
José Andrés Gómez Cantero General Director of Cima Universidad de Navarra
1. Cima
1.1. Organizational chart
The Foundation for Applied Medical Research (FIMA) is the owner of Cima. It is governed by a Board of Trustees, whose Chair is Enrique de Sendagorta. Members of the Board of Trustees: Jorge Lucaya (ViceChair), Igor Errasti (Secretary), Paloma Grau (Member), Miguel Sanz (Member) and Isabel Estapé (Member).
Honorary Members: Dr. Antonio Catalán, Javier Olave, Antonio Trueba and Francisco Errasti.
I. Cima governing bodies
a. Management Committee: José Andrés Gómez
Cantero, General Director; Dr. Jesús San Miguel, Director of Translational Medicine; Dr. Gloria González-Aseguinolaza, Director of Innovation and Translation; Dr. Antonio Pineda-Lucena, Scientific Director; María Mora, Manager and Dr. Ana Fortuño, Scientific Secretary.
b. Scientific Advisory Board: José Andrés Gómez
Cantero, Rubén Pío, Bruno Paiva, Felipe Prósper, Marta Alonso, Matías Ávila, Juan José Lasarte, Ignacio Melero, Maite Huarte, Gloria González Aseguinolaza, Ana García Osta, Puri Fortes, Antonio Pineda, Carlos Ortiz de Solórzano, Mikel Hernáez, Marta Ferrer, Bruno Sangro and Antonio González.
C. External Scientific Board: Margarita Del Val, Director of the Viral Immunology Unit at CSIC; Jean Charles Soria, Director of the Therapeutic Area of Oncology at Amgen; Dr. Juan Bueren, Head of the Division of Innovative Therapies in the Hematopoietic System at CIEMAT; Dr. Ángel Carracedo, Professor of Genomic Medicine at the Universidad de Santiago de Compostela; Miao Chih Tsai, Scientific Director of the RNA Medicine Program at Stanford University (United States); Francisco Sánchez Madrid, Scientific Director of the Instituto Sanitario Hospital La Princesa; Marcela Maus, Director of the Immunotherapy Program at Massachusetts General Hospital (United States); and Jude Samulski, Director of the Center for Gene Therapy at the University of North Carolina and founder of Askbio (United States).
II. Cima is a research institute of the Universidad de Navarra in application of Art. 10 of Organic Law 6 of December 21, 2001 on Universities.
1.2. Research organization: scientific programs and platforms
In the 2022-2023 academic year, Cima’s Management Committee modified the institution’s organizational structure with the aim of aligning its cancer research activity with the Cancer Center Clínica Universidad de Navarra, strengthening our recognized expertise in gene therapy and gene expression, and more effectively integrating technological capabilities.
The aim of this new organization is to promote innovation and transfer of our activity, and to develop multidisciplinary groups that can contribute to the discovery of new therapeutic solutions for the benefit of patients.
FUNCTIONAL STRUCTURE OF CIMA
DIVISIONS
CANCER DIVISION
Rubén Pío
Hemato-Oncology:
Bruno Paiva and Felipe Prósper
Solid Tumors:
Marta Alonso and Matías Ávila
Immunology and Immunotherapy:
Juan José Lasarte and Ignacio Melero
DNA AND RNA MEDICINE
DIVISION
Maite Huarte
Gene Therapy for Rare Diseases: Gloria González Aseguinolaza
Gene Therapy for Neurological Diseases: Ana García Osta
RNA Biology and Therapies: Puri Fortes
PLATFORMS
Cima has 10 technology platforms that provide services to the center’s research groups.
Biobank: Mª Antonia Fortuño
Morphology: Laura Guembe
Animal Production and Experimentation: Elena Ciordia
Genomics: Francesco Marchese
Cytometry: Bruno Paiva
Bioinformatics: Mikel Hernáez
Image: Carlos Ortiz de Solórzano
Micro-PET: Iván Peñuelas
Radioactive Facility: Lourdes Ortiz
Biochemical Analysis and Cell Metabolism: Eva Santamaría
TECHNOLOGICAL INNOVATION
DIVISION
Antonio Pineda-Lucena
Biomedical Engineering: Carlos Ortiz de Solórzano
Computational Biology and Translational Genomics: Mikel Hernáez
Cytometry: Bruno Paiva
Therapeutic Innovation: Antonio Pineda-Lucena
GENERAL SERVICES
The research activity carried out at Cima is managed by a Management Department in charge of ensuring that scientific production is properly directed, managed and coordinated.
General Management: María Mora
Financial Management and Administration: Laura Escudero
Research and Project Management: Diego Medarde
Translation and Innovation Unit: Antonio Pineda-Lucena
General Services: Carlos Embid
Personnel Services: Raquel Tornos
Institutional Development: Sandra Ramos
Communication: María Pilar Huarte
1.3. Information on the 2022-2023 academic year
1.3.1. Professionals: multidisciplinary teams
487 professionals work at Cima
1.3.2. Publications
301 scientific publications
244 in the first quartile
63 researchers
109 researchers in training
14 clinical researchers
142 research technicians
12 associate researchers
55 administration and services personnel
1.3.3. Competitive projects
76 competitive projects
69 national grants
45 postdoctoral researchers
47 technicians in bioinformatics and other categories
1.3.4. Innovation
Collaboration agreements for the promotion of research and technology transfer.
56 in total
13 R&D
(more information on pages 14 and 23)
4 licenses
34 technology services
7 international grants
5 others
1.3.5. Funding
23.100.000
Income earned in the academic year
Funding is obtained from three main pillars:
40% collaboration agreements (more information on page 23)
36% national and international competitive projects (more information on page 20)
24% nonprofit contributions from private individuals, companies and foundations (more information on page 34)
1.3.6. Media coverage
110 press releases +600 media citations
1.4. International dimension
INNOVATION AND KNOWLEDGE TRANSFER AGREEMENTS
New Jersey (BMS), Paris (Vivet), Basel, Switzerland (Roche), Wilmington, Delaware (United States) (Astrazeneca), Cambridge, United States (Moderna), Navarre (Viscofan), Barcelona (Hemostatics)
AGREEMENTS WITH INSTITUTIONS
Oxford, Israel
PROFESSIONALS FROM 18
COUNTRIES: Spain, Germany, Italy, United Kingdom, France, Bulgaria, Switzerland, Uganda, United States, Russia, India, Philippines, Mexico, Argentina, Colombia, Uruguay, Peru and Ecuador.
2. Scientific activity
2.1. Scientific output in figures
In 2022, Cima’s scientific activity resulted in:
First Quartile
publications
Average Impact Factor 13,26 Average Impact Factor + Signature publications IF Average
ISI CIT FIRST QUARTILE AVERAGE
2.2. Selection of publication highlights in 2022
Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma
Alonso MM et al. New England Journal of Medicine
Cancer Division
First Decile. Top 3
Teclistamab in Relapsed or Refractory Multiple Myeloma
San Miguel J et al. New England Journal of Medicine
Cancer Division
First Decile. Top 3
Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
Calvo A et al. Nature Medicine
Cancer Division
First Decile. Top 3
Transition to heart failure in hypertension: going to the heart of the matter
Diez J et al. European Heart Journal
Cardiovascular
First Decile. Top 3
IL-6/STAT3 signaling in tumor cells restricts the expression of frameshift-derived neoantigens by SMG1 induction
Pastor F. Molecular Cancer Technological Innovation Division
First Decile. Top 3
The deleterious effect of acetaminophen in cancer immunotherapy
Berraondo P et al. Annals of Oncology
Cancer Division
First Decile.
Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial
San Miguel J et al. Journal of Clinical Oncology
Cancer Division
First Decile.
Circulating Tumor Cells for the Staging of Patients With Newly Diagnosed Transplant-Eligible Multiple Myeloma
Paiva B et al. Journal of Clinical Oncology
Cancer Division
First Decile.
Tumor ENPP1 (CD203a)/ Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote PostRadiotherapy Local Recurrence in Breast Cancer
Lecanda F et al. Cancer Discovery
Cancer Division
First Decile.
CD137 (4-1BB)-Based Cancer
Immunotherapy on Its 25th Anniversary
Melero I et al. Cancer
Discovery
Cancer Division
First Decile.
A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells
Prósper F et al. Cell
Metabolism
Cancer Division
First Decile. Top 3
In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer
Dubrot J et al. Nature
Immunology
Cancer Division
First Decile.
Iberdomide with dexamethasone: a new backbone for myeloma treatment?
San Miguel J et al. The Lancet
Haematology
Cancer Division
First Decile. Top 3
Activation of the PP2A-B56 heterocomplex synergizes with venetoclax therapies in AML through BCL2 and MCL1 modulation
Odero MD et al. Blood
Cancer Division
First Decile. Top 3
Recombinant porphobilinogen deaminase targeted to the liver corrects enzymopenia in a mouse model of acute intermittent porphyria
Fontanellas A et al. Science
Traslational Medicine
Cancer Division
First Decile. Top 3
NaroNet: Discovery of tumor microenvironment elements from highly multiplexed images
Ortiz de Solórzano C et al. Medical Image Analysis
Technological Innovation Division
First Decile. Top 3
2.3. Competitive projects
The following was obtained in the 2022-2023 academic year:
76 competitive projects
69 national grants
Over €
Total amount in grants
7 international grants
8.300.000
2.4. Training and talent
2.4.1.
Scientific events
In the 2022-2023 academic year, monthly general sessions were held, along with weekly seminars led by Cima professionals and national and international guest speakers.
Sesiones generales
20/09/22 Leiden University Medical Center Gonzalo Sánchez-Duffhues
28/10/22 Gene Therapy and Regulation of the Gene Expression
28/11/22 Hemato-Oncology
16/12/22 Computational Biology
13/01/23 Cardiovascular Diseases
10/02/23 Regenerative Medicine
17/03/23 Solid Tumors
21/04/23 Neurosciences
22/05/23 Immunology and Immunotherapy
Gloria González Aseguinolaza
Juan Roberto Rodríguez
Idoia Ochoa
Carmen Roncal
Froilán Granero
Marta Alonso
Ana García Osta
Sandra Hervás
3. Traslation and Innovation
Cima focuses its work on developing a dynamic pipeline of patent-protected assets for the development of new drugs. Our discoveries therefore generate therapeutic and diagnostic alternatives that aim to meet current patient needs.
Among our most recent milestones are the agreements signed for the development and exploitation of viral vectors and technologies for gene therapy and cancer immunotherapy at Cima and protected by patents.
3.1. Patents and research management
In the 2022-2023 academic year:
6 patents generated
4 of which are owned by Cima
Since Cima was founded, its scientific activity has generated a total of 135 inventions at different stages of development that have been granted industrial protection. Cima currently has a portfolio of 39 active patents, 21 of which are its own property.
39 active patents
3.2. Innovation
The starting point of research into new drugs is understanding real patient needs and the mechanisms of the disease.
The first phases of discovery are carried out at Cima and then further development is carried out with the help of pharmaceutical companies until the drug is made available to patients.
During the 2022-2023 academic year, the following collaboration agreements were signed for the promotion of research and technology transfer:
56 total agreements signed
13 R&D 4 licenses 34 technological services
5 others
3.3. Other strategic alliances
Collaboration agreement with the University of Oxford
The University of Oxford and Universidad de Navarra signed an agreement to do research and apply new techniques in immunotherapy for cancer patients. This is the only active agreement in this field that a Spanish university has signed with the University of Oxford Nuffield Department of Medicine (NDM).
This agreement aims to boost scientific production at both institutions while sharing strategic initiatives and supporting clinical trials at both centers. Another goal is to promote undergraduate and postgraduate medical education at both universities. Faculty and student exchanges will be facilitated and new opportunities for working on research programs will be explored. Materials and publications will also be shared.
As part of this agreement, Dr. Ignacio Melero, co-director of the Immunology and Immunotherapy Program at Cima, has been appointed Professor (Kidani Chair of Oncology) at the University of Oxford.
Cancer research agreement with the Weizmann Institute of Science
Cima and the Weizmann Institute of Science in Israel signed a cancer research agreement. The aim of this agreement is to implement three pioneering biomedical projects that combine artificial intelligence, cutting-edge genetic technology and advanced therapies. These projects are designed to improve treatment of lung and pancreatic cancer, two of the most lethal tumors, as well as multiple myeloma, the second most frequent form of blood cancer.
The agreement was made possible thanks to the initiative and contribution of the Alberto Palatchi Foundation, a philanthropic organization with many goals, including the promotion of biomedical research and technological innovation.
4. Research to heal
With the fundamental goal of carrying out research to heal, our professionals focus their scientific activity on deciphering the mechanisms that cause diseases and treating them using innovative tools such as RNA medicine, gene therapy, cell therapy and immunotherapy.
Moreover, oncology research at Cima is integrated in the Cancer Center Clínica Universidad de Navarra, a comprehensive center presented in January 2023 to consolidate more than four decades of expertise in cancer training, research and medical care at the Universidad de Navarra.
Recognized as a Center of Excellence by the Scientific Foundation of the Spanish Association Against Cancer, it has been a member of the Organization of European Cancer Institutes (OECI) since June 2023, which represents a step toward its accreditation as a comprehensive cancer center.
550 medical specialists, researchers and educators
3.000+ new patients a year
4.1. Clinical trials
250+ research projects
Most of the ongoing clinical trials carried out at Clínica Universidad de Navarra in collaboration with Cima researchers are in the field of oncology.
At present, 25 Clínica Universidad de Navarra departments have ongoing trials in which Cima professionals participate. About 140 new trials are managed each year, and patients participated in 630 trials in the 20222023 academic year.
4.2. Research at the service of the patient
Achilles’ heel of lung cancer found
Researchers in Cima’s Solid Tumor Program made lung cancer respond to immunotherapy by inhibiting a kind of protein involved in tumor development. This finding laid the foundation for a new targeted therapy to treat this disease, which is the leading cause of cancer-related death in the world.
Specifically, scientists discovered that the Achilles’ heel of this tumor lies in the inhibition of DSTYK, a type of protein involved in tumor development. This protein is altered in a high percentage of patients, which makes it a new therapeutic target for treatment of this disease.
“This study recognizes the connection between the DSTYK protein and lung cancer for the first time, a finding that allows us to identify the patients who will not respond to immunotherapy,” said Karmele Valencia, a researcher in Cima’s Solid Tumors Program and the first author of the article. Furthermore, according to Luis Montuenga, senior investigator in Cima’s Solid Tumors Program and principal investigator of the study, “Prioritizing this new target will lay the foundation for drug development and clinical trials that can expand the percentage of patients who benefit from treatments based on immunotherapy.”
This work was published in the Journal of Experimental Medicine.
Peripheral blood test diagnoses multiple myeloma patients with greater accuracy and safety
Researchers from Cima’s Hemato-Oncology Program confirmed that a liquid biopsy (quantification of the tumor using a blood test) is a more effective and less invasive method for quantifying the tumor burden in patients with multiple myeloma.
Multiple myeloma is a kind of blood cancer that infiltrates the bone marrow and can spread throughout the skeleton by circulating tumor cells in the body, resulting in a poor prognosis for the patient. It is therefore essential to develop tools for real-time measurements of the proliferation and dissemination rate of each patient’s tumor.
“A liquid biopsy can improve staging and identify patient subgroups with a very good prognosis and others who actually have a case of plasma cell leukemia hidden under their myeloma and require different treatment. The goal is to understand the genetic characteristics of the tumor and the degree of tumor dissemination in order to detect the patient’s risk of progression as soon as possible,” explained Dr. Bruno Paiva, director of the Multiple Myeloma Group at Cima, which forms part of the Cancer Center Clínica Universidad de Navarra.
The study, conducted as part of a clinical trial of the Spanish Hematology Treatment Program (PETHEMA), involved recruiting samples from 374 patients newly diagnosed with multiple myeloma.
The results were published in the Journal of Clinical Oncology, a journal of great scientific impact in the field of oncology.
5. Cima and society
In order to serve society, our scientists participate in cultural, social and dissemination activities aimed at raising awareness about their scientific activity.
5.1. Dissemination activities
R&D MEETINGS
02|16|23
Reception of the organizers and speakers at the ICPerMed Workshop organized by the Government of Navarre
02|17|23
Retreat of CIBERONC coordinating groups
5.1. Dissemination activities
01|26|23
Doctor-patient conversation during the presentation of research grants from the Spanish Association Against Cancer in Navarre
08|14|23
Participation in the challenge ”Yo IN. ¿Y tú?” (I support childhood cancer research. What about you?), which raises funds for research in childhood cancer MEETINGS WITH PATIENTS
5.2. One year. A lot to be thankful for
700+
collaborators
In this fiscal year, more than 700 collaborators made financial contributions to enhance progress in our understanding and treatment of cancer, rare diseases, neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and heart disease.
Each collaborator has had a very significant impact on our research. We greatly appreciate the trust and solidarity shown throughout the year by individuals, companies and foundations, which make our mission of research to heal possible. Your support encourages us to keep moving forward to achieve our goals for the benefit of society as a whole.
Forms of collaboration
Once again this year, we received the generosity of our collaborators in a variety of ways:
• By funding a specific line of research in necessary areas such as cancer research and rare diseases Every euro spent on research is essential to find a cure for rare diseases, oncological diseases and others.
• By providing support for training and the scientific development of young research talent by financing a four-year predoctoral grant or postdoctoral fellowship.
• By showing solidarity by leaving an inheritance or bequest in favor of Cima. An inheritance or solidarity last will is an act of perpetual generosity, commitment to research and a way to participate in future advances in biomedical research.
• By creating a memorial scholarship where family and friends pay tribute to loved ones by creating a grant in their name to research a disease that has had a personal impact on them.
We are very grateful to all the people who collaborated with us this year through their financial contributions, solidarity bequests and memorial scholarships. Thanks to the families who have placed their trust in our researchers. The laboratories receiving these funds have expanded and have been able to increase their lines of research and make faster progress in the search for effective treatments.
Together we research to heal.
The footprint of our donors
The donations received this year played a key role in our ongoing effort to understand diseases in order to improve diagnoses and develop therapeutic strategies to address them.
Each contribution helps fund our lines of research, innovative therapies and programs to improve the diagnostics and treatment of different diseases or to the Cima research fund. The collaboration of our donors has allowed us to make progress with key research, preclinical trials and projects that ultimately seek to relieve suffering and improve the quality of life of the people affected by these diseases.
ADEY FOUNDATION
Cima and the Adey Foundation signed an agreement to promote gene therapy research for Alzheimer’s disease at Cima. The Adey Foundation is a non-profit organization that promotes scientific development by granting financial aid to organizations that promote teaching activities and research projects. Thanks to your help, we research to heal.
5.3. Cima in the media
The progress made at Cima has resulted in 110 press releases, which have been covered in more than 600 national and international media venues.
Social media 110 press releases
641 media venues
88 print media
2,087 new followers and 244,598 printed pages
114 followers, 3,507 visits
Scope estimate: 598,883 (account reopened in May 2023)
436 digital media
29 national television and radio stations
356 new followers and 299,200 printed pages
73 followers, 455 visits
Scope estimate: 139,875 (account opened in May 2023)
88 international media venues
INTERNATIONAL MEDIA
SALUD
“EL ESTRÉS ES EL PEOR FACTOR DE RIESGO PARA LA SALUD”
Salud mental. El neurobiólogo israelí Alon Chen lleva décadas estudiando los efectos del estrés en nuestro organismo. “La clave ahora es entender por qué algunas personas son más resilientes para tratar de imitar ese mecanismo”
Por Cristina G. Lucio
El cerebro siempre le había fascinado, pero Alon Chen (Be’er-Sheva, Israel, 1970) no tuvo verdaderamente claro que quería dedicarse a la neurociencia hasta que hizo el servicio militar. Como la mayoría de israelíes, el investigador fue recluta entre los 18 y los 21 años, una experiencia que marcó su futuro. «Lo que vi y lo que viví me hizo querer entender qué pasa en nuestros cerebros cuando sufrimos estrés, qué mecanismos están implicados», cuenta. «Eso es a lo que llevo dedicando mi investigación más de 20 años», .
El neurobiólogo combina su labor como investigador con la presidencia del Instituto Weizmann, una reconocida institución científica israelí que acaba de firmar un convenio de colaboración con el CIMA Universidad de Navarra con el objetivo de mejorar los tratamientos para el mieloma y los cánceres de pulmón y páncreas. Chen pasó unos días en Pamplona para cerrar el acuerdo.
P. ¿Para qué sirve el estrés? ¿Por qué lo tenemos?
R. Es una pregunta que se hacen muchas personas: «¿Por qué el cerebro me hace esto?» Pero hay que recordar que el estrés es una respuesta de supervivencia. Es una respuesta compartida con muchas especies, que se conserva a lo largo de la evolución. Está diseñada para protegernos frente a un desafío. Si estás cazando y aparece un depredador, tienes que poder escapar de esa amenaza. El estrés hace que tu frecuencia cardiaca suba, que se incremente tu presión
arterial, tu cortisol o incluso tus niveles de glucosa en sangre. Tu respiración también cambia, al igual que tu sistema cognitivo. Al ver a un león tu cerebro prepara a tu organismo al completo para que pueda disponer de la suficiente energía y capacidad para escapar. Es una respuesta saludable, necesaria. Si luego te das cuenta de que no era un león, esa respuesta debe apagarse, tu organismo debe volver al estado inicial. El problema es que muchas personas tienen problemas a la hora de regular ese apagado. Y en el mundo en que vivimos el león se ha transformado en otras cosas: el contrato que tienes que firmar, el plazo que tienes que cumplir, un examen, que alguien esté tratando mal a tus hijos en las redes sociales... Los estresores han cambiado de modo que ahora mismo el estrés es el principal factor de riesgo ambiental que puede afectar a tu salud.
P. ¿Qué es lo que provoca en nuestra salud?
R. Conocemos un poco mejor los mecanismos que hacen que el estrés cause trastornos como la ansiedad, la depresión, los trastornos alimentarios o el estrés postraumático, pero el estrés se relaciona con muchos otros problemas de salud cuyos lazos conocemos mucho peor. Sabemos que el estrés puede afectar a muchísimas facetas, como la inmunitaria, la metabólica o incluso la reproductiva, pero tenemos que seguir estudiando por qué y de qué manera. Al igual que tenemos que seguir estudiando por qué unas personas son más resilientes al estrés que otras o por qué el estrés afecta de forma diferente a hombres y mujeres.
P. ¿Qué es lo que han podido averiguar hasta ahora sobre por qué algunas personas soportan mejor el estrés?
diferente a hombres y mujeres. ¿Qué saben de esas diferencias?
R. Durante años, la investigación se centró principalmente en el sexo masculino. Incluso en los estudios preclínicos en animales; se hacían con machos por una cuestión de dinero. Los animales hembra o las mujeres tienen ciclos hormonales que exigen estudios diferenciados en función de en qué momento del ciclo estén. Necesitas, por tanto, diferentes grupos de control. Hace solo una década, los Institutos Nacionales de Salud de EEUU obligaron a que los estudios se hiciesen con ejemplares e individuos tanto de sexo masculino como femenino. Sabemos que hombres y mujeres no responden, en general, igual al estrés. Tanto la respuesta hormonal como la de comportamiento son diferentes. Por ejemplo, la segregación de cortisol, la llamada hormona del estrés, es de media tres veces más
“Sabemos que hombres y mujeres no responden igual al estrés. Tanto la respuesta hormonal como de comportamiento son distintos. Pero seguimos tratándoles igual”
R. Saber qué hace a algunas personas resilientes es una de las preguntas más importantes que se plantea la Neurociencia en general a día de hoy. Durante más de 100 años, la investigación se ha centrado en la enfermedad, en saber por qué muchas personas sometidas a estrés desarrollaban problemas de ansiedad o depresión, entre otras. La gran pregunta que tenemos que hacernos ahora es por qué tantas personas son resilientes. Si enviamos a un grupo de soldados a una zona de guerra, todos ellos se van a enfrentar a experiencias traumáticas. Cuando vuelvan a casa, un 15% de ellos aproximadamente desarrollará estrés postraumático, mientras que el 85% no lo hará. Hasta ahora nos hemos centrado en el 15%, pero la pregunta que hay que responder ahora es por qué ese 85% que ha vivido lo mismo ha sido resiliente. Lo que sabemos hasta ahora es que los mecanismos que hacen a una persona más resiliente o más vulnerable al estrés son distintos, son circuitos paralelos. Conocer mejor los genes, las proteínas, los canales que hacen a una persona más resiliente puede ayudarnos a imitar esos mecanismos para ayudar a los más vulnerables, teniendo siempre en cuenta de que tanto la resiliencia como la susceptibilidad no son cuestiones que solo dependan de los genes. Son una combinación de factores genéticos y ambientales.
“Está muy demostrado que hacer ejercicio ayuda a combatir el estrés. También es muy importante la interacción con otras personas. Somos seres sociales”
P. Señalaba que el estrés afecta de forma
alta en mujeres que en hombres. También que la depresión y la ansiedad, patologías mediadas por el estrés, son de dos a tres veces más frecuentes en mujeres. Y pese a eso, estamos tratando igual el estrés y estas patologías en hombres y mujeres. Creo que es fundamental estudiar a fondo estas diferencias entre sexos, porque podría suponer un cambio en los abordajes.
P. Hasta que sepamos esos datos, ¿qué dice la evidencia científica que es lo mejor que podemos hacer para combatir el estrés?
R. Definitivamente, el estrés es un problema importante que afecta a una gran cantidad de personas. Reducirlo resultaría muy beneficioso para todos y hay varias maneras de conseguirlo. La forma que cuenta con mayor respaldo científico es la actividad deportiva. Está muy demostrado que hacer ejercicio es beneficioso. No hace falta hacer un iron man. Estar activo, practicar una actividad física tiene un impacto beneficioso en el cerebro. Dicho esto, hay que tener en cuenta que a una persona que tiene depresión y que apenas
El investigador israelí y presidente del Instituto Weizmann, Alon Chen, durante una reciente visita a Pamplona.
Domingo 25 de junio de 2023 PAPEL La revista dominical de EL MUNDO
puede levantarse de la cama hay que darle otras soluciones. En esos casos no sirve decirle que tiene que hacer ejercicio. Todo lo que genere lo que denominamos enriquecimiento también puede ayudar. Aquellas cosas que nos hacen sentir bien en función de nuestros gustos: a unos les va bien ir de pesca, a otros leer, hacer tareas de jardinería... Esas actividades ayudan a rebajar los niveles de estrés. También hay evidencias de que la meditación y el mindfulness puede tener beneficios. Y es muy, muy importante la interacción con otras personas, lo hemos visto en la pandemia. Somos seres sociales que necesitamos el contacto con otras personas. La psicoterapia también funciona. Se sabe que la psicoterapia, tras un año de tratamiento, es tan eficiente como cualquiera de los fármacos antidepresivos que están disponibles. El problema es que en muchos países conseguir una cita con un psicólogo puede llevar meses.
P. ¿Cuál es el impacto que el Covid ha dejado en nuestros cerebros?
R. Ha tenido un gran impacto. Cómo ha aumentado la ansiedad, por ejemplo, en jóvenes, niños y
Imágenes en distintos planos del cerebro humano, obtenidas a través de una tomografía axial computarizada.
adolescentes. Hemos visto un incremento en los casos de estrés postraumático y un dramático aumento de los suicidios y la ideación suicida. Es un grave problema que no ha terminado, seguimos sufriendo los efectos de la pandemia sobre la salud mental.
P. ¿Es necesaria una mayor inversión en salud mental a nivel global?
R. Sin duda. La salud mental es ahora mismo una caja negra. Le daré un ejemplo de hasta qué punto esto es así: hoy si uno tiene cáncer hay un gran número de pruebas, análisis de sangre, escáner, resonancia magnética, histología, etc. que dan datos sobre cómo es ese tumor y qué tratamientos pueden funcionar mejor. Hay medidas cuantitativas que permiten identificarlo y definir el mejor abordaje. ¿Qué tenemos para la salud mental? No hay ni análisis, ni pruebas de imagen ni nada que permita realizar el mejor diagnóstico para buscar el mejor tratamiento. Estamos 20 años por detrás con respecto al cáncer. Creo que la inteligencia artificial puede ser importante en ese sentido y podrá ayudar, por ejemplo, a identificar la firma genética que hace a algunas personas más vulnerables a sufrir problemas como la depresión.
Hace 20 años, secuenciar el primer genoma humano costó mil millones de dólares. Hoy esa secuenciación puede hacerse por unos 100 dólares. Y los avances en inteligencia artificial permiten leer cientos de miles de datos en poco tiempo. Creo que no estamos lejos de ir encontrando algunas respuestas.
P. ¿Cómo ve el futuro de la investigación?
R. La ciencia ha de ser un empeño internacional. Colaboraciones como la que hemos firmado con el CIMA Universidad de Navarra en el Instituto Weizmann son extremadamente importantes. Si hacemos ciencia en silos independientes no podremos ser expertos en nada. Promover la colaboración científica es esencial porque la ciencia hoy en día es muy dependiente de la tecnología y requiere una gran inversión. Las compañías, los gobiernos, la gente debe apostar por la ciencia. Lo hemos visto durante la pandemia: las soluciones vinieron de la ciencia y, sin duda, empresas como Moderna o Pfizer hicieron un gran trabajo. Pero lo que consiguieron en tiempo récord fue gracias a las décadas de estudios en inmunología, virología o biología que se habían hecho antes, muchas de ellas en instituciones de investigación académicas.
PAPEL La revista dominical de EL MUNDO Domingo 25 de junio de 2023
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