Noticias

The Spanish Society of Medical Oncology (SEOM) acknowledges Maria Alsina and Hugo Arasanz, HUN oncologists and researchers at Navarrabiomed

Author
Navarrabiomed

Professionals from the Medical Oncology Service of the University Hospital of Navarra (HUN) and Navarrabiomed have received two fellowships and an award during the annual congress of the Spanish Society of Medical Oncology (SEOM) 2023, held in Barcelona from the 19th to the 22nd of September. 

In particular, Maria Alsina Maqueda  MD PhD has received the SEOM Fellowship for Research Projects for 'Predictive biomarkers of response to RAPID scheme neoadjuvance in locally advanced rectal cancer: impact of the intestinal microbiome and the presence of circulating tumour DNA (ctDNA)’, in which several HUN services are also involved. For his part, Hugo Arasanz Esteban MD PhD has been awarded the SEOM Fellowship for Translational Research Projects in Immuno-Oncology for the project 'Circulating low density neutrophils and their role in immunotherapy resistance in non-small cell lung cancer. Potential as a predictive biomarker’. 

Both Medical Oncology specialists dedicate part of their time to research at the Oncobiona group of Navarrabiomed. Dr Alsina researches through the Navarrabiomed intensification program funded by La Caixa Foundation and Dr Arasanz thanks to the 2019 AECC Junior Clinical Fellowship, from the Spanish Association against Cancer.
 

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Professionals of the Medical Oncology Service of the HUN.
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Hugo Arasanz Esteban.
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Maria Alsina Maqueda.
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AES 2024: novedades y formación específica para la preparación de propuestas

Author
Navarrabiomed


La Acción Estratégica en Salud es la principal herramienta para financiar la investigación biomédica y sanitaria en España y está gestionada por el Instituto de Salud Carlos III (ISCIII), como organismo dependiente del Ministerio de Ciencia, Innovación y Universidades.

La AES 2024 contará para el año próximo en su primera convocatoria, ya publicada en el Boletín Oficial del Estado (BOE), con más de 138 millones de euros para financiar convocatorias de ayudas, proyectos y contratos de investigación en salud. Esta cifra inicial se podrá ampliar con hasta 40 millones adicionales y se complementará con otras convocatorias adicionales que se lanzarán a lo largo de los próximos meses; la previsión es movilizar casi 285 millones de euros para la investigación en salud en España en el marco de la AES 2024.

A través de fondos públicos y en convocatorias de concurrencia competitiva, la AES del ISCIII concede anualmente ayudas económicas para la realización de contratos y de proyectos de investigación que impulsen la I+D+I biomédica y sanitaria en España y la carrera profesional de su comunidad investigadora. En las próximas semanas se anunciará la fecha de presentación formal de esta primera convocatoria de la AES 2024, incluyendo todos los aspectos técnicos y administrativos necesarios para su desarrollo. ​

Como en los últimos años, la AES cuenta con un corpus de convocatorias en el que se incorporan actuaciones innovadoras, dando como resultado una Acción Estratégica en Salud constituida por convocatorias muy conectadas y sinérgicas. El director del ISCIII, Cristóbal Belda​, explica que la AES y su contenido evolucionan en función de las necesidades del sistema: “La progresiva incorporación de fondos al presupuesto inicial es uno de los elementos centrales de la nueva forma de entender la financiación necesaria dentro del Sistema Nacional de Salud (SNS) y del Sistema Española de Ciencia, tecnología e Innovación (SECTI) en el ámbito biomédico y sanitario, que nos dota de una especial flexibilidad para seguir impulsando la I+D+I en salud".

De esta manera, esta primera convocatoria podrá alcanzar los 178,3 millones para diversas actuaciones, entre los que se encuentran los Contratos Miguel Servet, Juan Rodés, Río Hortega y Sara Borrell; las Ayudas para la movilidad del personal investigador; los Proyectos de I+D+I en salud; los Proyectos de investigación clínica independiente (ICI), y los Proyectos de colaboración internacional, entre otros.

Además de estos fondos, la financiación aumentará para apoyar convocatorias adicionales que se lanzarán próximamente, algunas de ellas vinculadas al PERTE para la Salud de Vanguardia. En total se prevé la disponibilidad de cerca de 150 millones adicionales distribuidos en 120 millones en subvenciones, hasta alcanzar los casi 285 millones, que incluirán una convocatoria de investigación en red y 27 millones en préstamos para entidades públicas.


Novedades para 2024


Como cada año, la AES consolida las mejoras aplicadas en convocatorias previas, e incluye novedades para seguir potenciando su capacidad. En 2024 se consolidará su evaluación y adhesión a los principios de la Declaración de San Francisco (DORA), consolidando el análisis cualitativo del impacto social de la ciencia en la evaluación de los proyectos financiados con fondos públicos.

También se progresa en las modificaciones introducidas con la reforma de la Ley de la Ciencia , dirigidas a consolidar una financiación creciente y progresiva; simplificar el procedimiento administrativo vinculado a la gestión de la investigación; impulsar la contratación indefinida; mejorar el itinerario posdoctoral; promover nuevos derechos laborales para los jóvenes; favorecen el recambio generacional y la transición de liderazgo; lograr mayor movilidad profesional; fomentar la transferencia de conocimiento, y garantizar la igualdad de género.

La AES 2024 seguirá fomentando la creación de puestos de trabajo permanentes vinculados a los programas post-doctorales de excelencia, como son los contratos Miguel Servet y Juan Rodés. Una de las novedades para el próximo año desarrolla la estrategia del ISCIII orientada a la promoción de la investigación en Atención Primaria, incluyendo acciones internacionales especialmente enfocadas a este ámbito, y al fortalecimiento de la transferencia de los resultados de la investigación, al incorporar como beneficiarios en acciones específicas a los centros tecnológicos.

Otra de las novedades es la ampliación de la posibilidad de realizar actividades docentes para las personas vinculadas a contratos predoctorales. También destacan el aumento de la duración de las estancias formativas, así como la ampliación en la realización de actividades asistenciales para los beneficiarios de ayudas vinculadas a centros con actividad clínico-asistencial. Además, se avanza en la simplificación administrativa en la gestión de solicitudes.

Por otro lado, la AES 2024 abre la participación a la primera convocatoria europea de ayudas ligada a la reciente aprobación por la Comisión Europea del Partenariado de Medicina Personalizada de Precisión EP PER MED. También se añade a las actuaciones europeas y transnacionales un especial foco en la internacionalización de la investigación realizada desde Atención Primaria.

En cuanto a las líneas de investigación que se beneficiarán de las convocatorias, la AES del próximo año consolida y amplía las orientadas a la protección de la salud y el impacto social de políticas sanitarias a diversas áreas estratégicas: 

  • Quimioprevención del cáncer en personas sanas.
  • Efectos terapéuticos a largo plazo en largos supervivientes de cáncer.
  • Calidad de vida en enfermedades crónicas, en especial las ligadas a fragilidad y vulnerabilidad social.
  • Impacto del consumo de alcohol y otros tóxicos en la salud.
  • Desarrollo y aplicación de herramientas conductuales y biológicas con aplicación en medicina de precisión y salud pública.
  • Nuevos sistemas de vigilancia epidemiológica con análisis de interoperabilidad y coste-efectividad.
  • Economía de la salud y farmacoeconomía.
  • Análisis de viabilidad de cribados poblacionales en patologías altamente letales y/o de elevada incidencia.
     

En definitiva, tal y como resume el director del ISCIII, "esta nueva convocatoria de la Acción Estratégica en Salud busca seguir impulsando la I+D+I en salud en España, facilitando el desarrollo de la carrera investigadora, ofreciendo oportunidades para que nuestras investigadoras e investigadores hagan ciencia biomédica de la más alta calidad, y poniendo el foco en solucionar las necesidades sociales para seguir mejorando la salud de las personas". 
 

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Navarrabiomed is coordinating SENSORFIT-4HEART, aimed at obtaining personalised treatment for patients with HFpEF

SENSORFIT-4HEART
Author
Navarrabiomed

 

  • This initiative, funded by the Government of Navarra, proposes a specific physical exercise programme for patients with heart failure with preserved ejection fraction. 

 

The partners of the SENSORFIT-4HEART project met at Navarrabiomed to begin work on this project, whose aim is to create an innovative platform for prescribing and remote-monitoring individualised physical exercise in the treatment of heart failure with preserved ejection fraction. The Principal Investigator of the Physical Exercise, Health and Quality of life Unit (E-FIT) of Navarrabiomed and full professor at UPNA Mikel Izquierdo and the UPNA associate professor Robinson Ramirez-Vélez are at the head of this strategic initiative funded by the Government of Navarra. 

Specifically, the Department of Industry and Ecological and Digital Business Transition has granted 1,147,000 euros to SENSORFIT-4HEART, through the call for grants for the implementation of strategic R&D projects 2023 - Challenge 7 SIBERIA V Innovative Solutions in Biotechnology. The project consortium is made up of the biomedical research centre Navarrabiomed, which is coordinating its implementation, ADItech, Cima Universidad de Navarra, Naitec and the companies Lorpeland and 540. Together they form a comprehensive team of professionals from very different fields, who are going to work together to implement this project in order to develop a strategy that allows progress to be made towards the personalised treatment of patients with heart failure with preserved ejection fraction (HFpEF), using non-pharmacological strategies that focus on their capacity for self-management and on improving their quality of life.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with an increasing incidence and poor prognosis, which already accounts for 50% of heart failure cases. This pathology is associated with ageing and cardiovascular risk factors such as high blood pressure, diabetes and obesity and is more common in women than in men. Sufferers often experience dyspnoea, debilitating fatigue, and poor quality of life, as well as frequent hospitalisations and a high mortality rate. Despite their great impact, most of the available pharmacological treatments for heart failure have not demonstrated a beneficial prognostic effect in patients with HFpEF. And although the syndrome is more common in women, they are typically under-represented in clinical trials and intervention studies. Therefore, SENSORFIT-4HEART will integrate the gender perspective throughout the implementation of the project in order to assess the incidence and impact on both sexes. 

The SENSORFIT-4HEART project will make it possible to implement an individualised physical exercise programme, two days a week, on HFpEF patients that will have a beneficial effect on their physical function and cardiac remodelling, as well as on muscular bioenergetics, functional capacity and quality of life. Furthermore, it is hoped it will contribute to the improvement of the prognosis of patients with HFpEF and to alleviate the burden this represents for the Navarra Health Service-Osasunbidea.

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Miembros del consorcio SENSORFIT-4HEART
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Launch meeting for the SENSORFIT-4HEART project
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SENSORFIT-4HEART follow-up meeting
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Control on the impact of physical exercise on the patient
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Reunión de seguimiento, junio 2024
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Mikel Izquierdo con su equipo de Navarrabiomed
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Adjudicación de las ayudas predoctoral y postdoctoral Navarrabiomed 2023 y puntuaciones finales de las y los solicitantes evaluados

Author
Navarrabiomed

La Comisión Técnica de Evaluación de Navarrabiomed ha publicado hoy martes, 26 de diciembre la adjudicación de las ayuda predoctoral y ayuda postdoctoral Navarrabiomed 2023, así como las puntuaciones finales de las y los solicitantes evaluados para cada una de las convocatorias: ayuda predoctoral y ayuda postdoctoral. A continuación, puede consultar y descargar la documentación correspondiente.

 

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Documentación
Programa de ayuda predoctoral Navarrabiomed 2023
26/12/23 - Adjudicación de la ayuda predoctoral
Programa de ayuda predoctoral Navarrabiomed 2023
26/12/23 - Puntuaciones finales de la ayuda predoctoral
Programa de ayuda postdoctoral Navarrabiomed 2023
26/12/23 - Adjudicación de la ayuda postdoctoral
Programa de ayuda postdoctoral Navarrabiomed 2023
26/12/23 - Puntuaciones finales de la ayuda postdoctoral
Programa de ayuda predoctoral Navarrabiomed 2023
12/12/23 - Propuesta de adjudicación de la ayuda postdoctoral
Programa de ayuda predoctoral Navarrabiomed 2023
12/12/23 - Puntuaciones de la ayuda predoctoral
Programa de ayuda postdoctoral Navarrabiomed 2023
12/12/23 - Propuesta de adjudicación de la ayuda postdoctoral
Programa de ayuda postdoctoral Navarrabiomed 2023
12/12/23 - Puntuaciones de la ayuda postdoctoral
Programa de ayuda predoctoral Navarrabiomed 2023
01/12/23 - Relación definitiva personas admitidas y no admitidas a la ayuda predoctoral
Programa de ayuda postdoctoral Navarrabiomed 2023
01/12/23 - Relación definitiva personas admitidas y no admitidas a la ayuda postdoctoral
Programa de ayuda predoctoral Navarrabiomed 2023
22/11/23 - Relación provisional personas admitidas y no admitidas a la ayuda predoctoral
Programa de ayuda postdoctoral Navarrabiomed 2023
22/11/23 - Relación provisional personas admitidas y no admitidas a la ayuda postdoctoral
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Navarra boosts health research to guarantee quality medical care

Author
Navarrabiomed
  • Vice Chair Ollo opened a conference organized by Navarrabiomed and the Directorate General for External Action to strengthen public health taking advantage of the European framework

The Condestable Palace of Pamplona / Iruña hosted this afternoon the meeting “Public health: researching and progressing with Europe - Scientific progress that saves lives”, whose objective was to convey to citizens the European Union's commitment to public health and biomedical research as a guarantee of innovative, sustainable and high-quality medical care. 

The conference, organized by the Navarrabiomed biomedical research centre and funded by the General Directorate of External Action of the Government of Navarra, through the 2023 call for Grants for the dissemination of European Union policies and strategies, has been an opportunity to remind us all that research and scientific progress saves lives.

During the institutional opening, the second vice-chair and Regional Minister of Memory and Coexistence, External Action and Basque Language and Literature, Ana Ollo Hualde, highlighted that “this conference represents a meeting point between three key lines for the development of Navarra: public health, research and the European framework”. 

 

A journey through the milestones of medical science over time

From an informative approach, the doctor, writer, scientific populariser and professor of the History of Medicine, Pedro Gargantilla Madera, then made a tour through the history of medicine reviewing the milestones of medical science over time and its decisive importance in the advancement of humanity.

Analysing the scientific advances that save lives, he explained that throughout the twentieth century there were “more scientific advances than in all previous centuries together." In the twentieth century the first antibiotics and insulin emerged, “a treatment that completely revolutionized the field of endocrinology.” Another relevant milestone was the marked by electrocardiogram that made it possible to reach a correct and accurate diagnosis in cardiovascular diseases.

On the other hand, he focused on the role of Europe throughout the history of medicine. "It was precisely in our continent where the transition from Mythos to Logos took place, back in the fifth century BC, in the first universities, with the appearance of autopsies that revolutionized medical knowledge and, in the twentieth century, the discovery of X-rays and penicillin. Until the Second World War, our continent championed medical knowledge," he explained.  

 
Public health: researching and improving with Europe 

Antonio López Andrés, Director General of Health of the Government of Navarra, has highlighted the research needs of the Health Department itself, based on its prioritization and health strategies. According to López: "This research should not be just a research "per se" but should keep an eye on the health needs and challenges presented by the population.” In this regard, the Director General mentioned the different actions to promote health research, such as the greater weight in professional careers or an adaptation of the care burden so that professionals can achieve this goal, especially in the field of primary care.

Conference attendees were able to learn more about the European commitment to health research from Laura Sesma Aguirre, leader of the Health Area in European Projects of Zabala Innovation. She stressed that people are living longer but “it's not just about giving life more years, but also giving those years more life. It is essential to work at all stages of life, so that healthy lifestyle habits can be acquired to prevent the onset of diseases. And to achieve this change, the European Union is aware of the need to involve all stakeholders of the health ecosystem from the start, including citizens. She insists that “we must be aware of the importance of these advances of which we are part and which will also affect us, in order to contribute ideas and solutions and also include these advances consciously and actively to really achieve change.”

For her part, Berta Ibáñez Beroiz, researcher at Navarrabiomed and head of the Methodology - Evaluation of Health Services Unit, insisted that research contributes to improving the health and well-being of the population, caring for their needs with a quality and efficient service. In this regard, she stressed that Europe enables a space to establish strategic collaborations that allow “to develop an increasingly competitive research and oriented to the problems that arise at the bedside of patients.” Berta Ibáñez added that “we are working to provide citizens with access to new therapies and more advanced diagnostic techniques. Research also means welcoming new methodologies, more open to society and evaluating health services to improve public policies. Research contributes to making the public health system more versatile, more rigorous and more competent.”


The exhibition "From the cell to the patient" at the Condestable Palace

Starting today and until December 10th, 2023, the exhibition "From the cell to the patient. 10 Years moving forward together", can be visited in the entrance hall of the Palace. To enjoy all the contents, download the free Navarrabiomed app (available for Android and for iOS).

This project has received funding from the Department of University, Innovation and Digital Transformation of the Government of Navarra in the call for Grants for the Promotion of Scientific Culture, the dissemination of R&D&I carried out in Navarra and the promotion of STEM COSMOS 2022 and 2023 vocations.
 

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Berta Ibáñez, Antonio López, Ana Ollo, Pedro Gargantilla and Laura Sesma.
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Pedro Gargantilla, doctor, writer, scientific populariser and professor of the History of Medicine
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Round table with the four experts.
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Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy

Author
Navarrabiomed

A study led by Navarrabiomed proposes a therapeutic alternative to treat melanoma.

  • The drug ranolazine, used to treat chronic angina pectoris, could improve response to anti-melanoma therapies.
  • This is a multicenter investigation carried out by Navarrabiomed biomedical research center, the Institute for Neurosciences CSIC-UMH, and IRB Barcelona.

The prestigious journal Nature Metabolism has published the results of a study in mice that determined that ranolazine, a drug that is currently administered to patients to treat heart conditions, delays the appearance of resistance to melanoma treatments, by blocking fatty acids metabolism. This research has been led by Navarrabiomed, together with the Institute for Neurosciences (CSIC-UMH) and IRB Barcelona. Melanoma is the most aggressive type of skin cancer and, although it only accounts for 10% of skin cancer cases, it is responsible for 90% of deaths associated with skin tumours. Thanks to the development of targeted therapies and immunotherapies, the clinical management of patients affected with this type of cancer has improved, however, these therapies still have limitations because 50% of patients do not respond adequately and even develop resistance.

The evidence suggests that this resistance could be linked to metabolic reprogramming in cancer cells that is associated to changes in the way in which cells process and use nutrients. This research demonstrates that fatty acid metabolism plays an important role in the development of resistance to melanoma treatments.

Researchers have confirmed that increased fatty acid oxidation occurs during long-term treatment with BRAF inhibitors, one of the key genes in tumour progression, contributing to therapy resistance.

Ranolazine increases the efficacy of targeted therapy against melanoma because it can target fatty acid oxidation. In addition, the application of this drug promotes that melanoma cells become more visible to the immune system,improving the response to immunotherapies and increasing the ability of lymphocytes to control tumour growth.

A multicenter investigation

The Navarrabiomed Cancer Signaling Unit, directed by Imanol Arozarena Martinicorena, has coordinated the course of the research and has been in charge of carrying out the experiments related to resistance to targeted therapies and the study of how ranolazine affects the immunogenicity of melanoma cells.

Researchers at the laboratory led by Berta Sánchez-Laorden, belonging to the Cell Plasticity in Development and Disease group at the Institute for Neurosciences, have developed immunotherapy experiments in mice and have carried out the study of immune cells in the tumour microenvironment.

In addition, the IRB Barcelona Stem Cells and Cancer research group, led by Salvador Aznar-Benitah, has carried out individual cell RNA sequencing analyses, which have made it possible to find out in detail the effect of the drug on the state metabolism of tumour cells.

Funding

This study, which has been made possible thanks to funding granted by the Ministry of Science and Innovation, the Carlos III Health Institute, the Government of Navarra, the Spanish Multidisciplinary Melanoma Group (GEM), and the Melanoma Research Alliance, is a clear example of how basic research can contribute a lot to the repositioning of drugs, which makes it possible to significantly shorten the deadlines for providing answers to patients suffering from diseases as prevalent as cancer.

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Marta Redondo and Imanol Arozarena, responsible for this research in Navarrabiomed
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Single cell sequencing analysis of different immune populations infiltrating untreated melanoma tumors or treated with ranolazine (Rano), immunotherapy (PDL1) or the combination of both (PDL1+Rano).
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Treatment with ranolazine increases the number of antitumour lymphocytes (green) that infiltrate the tumour(b lue) and favour the action of immunotherapy
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• The INNOLFACT project studies the direct relationship of the sense of smell with the immune system and neurodegenerative diseases such as Alzheimer's or Parkinson's

Author
Navarrabiomed
  • Today, World Brain Day, the benefits of this strategic R&D project funded by Economic Development and carried out by a consortium led by Navarrabiomed have been announced.

The Navarrabiomed biomedical research centre has recently hosted the final meeting of the INNOLFACT strategic project. During the event, chaired by the General Director of Industry, Energy and Strategic Projects S4 Uxue Itoiz, the results of the study were announced. The meeting was attended by representatives of the various institutions that make up the consortium, a multidisciplinary working group that includes a representation of the Navarra health ecosystem, both from the private and public sides.

The consortium is led from the Clinical Neuroproteomics Unit of Navarrabiomed, under the direction of its principal investigator Enrique Santamaría Martínez. In all, 75 professionals belonging to the Geriatrics Unit from Navarrabiomed and the University Hospital of Navarra (HUN), Cima University of Navarra, University of Navarra Clinic, ADItech and the company Ojer Pharma. 

The Department of Economic and Business Development, through the General Directorate of Industry, Energy and Strategic Projects S4, has financed the strategic R&D project INNOLFACT, which studies the direct relationship of the sense of smell with the immune system and neurodegenerative diseases. Thanks to this research, it will be possible to advance in an olfactory precision medicine capable of early diagnosis and developing immunomodulatory nasal therapies for the treatment of neurodegenerative diseases such as Alzheimer's or Parkinson's.


The project has received a total funding of 1,593,000 euros from the Department of Economic and Business Development of the Government of Navarra, through the call for Grants for strategic R&D projects 2020-2022. In addition, it should be noted that the consortium has submitted a continuation of the project to the call for Grants for strategic R&D projects 2023-2026 and has been selected as one of the projects that will receive funding.

Developing olfactory precision medicine 

In an aging society, the scientific community believes that disruptive approaches are needed to generate innovative tools to detect and diagnose neurodegenerative diseases early. Previous studies carried out in Navarra demonstrate the direct association of the sense of smell with the immune system and its impact on cognitive and motor functions. The INNOLFACT project delves into this field of research to characterize in depth the olfactory-immune system-brain axis and, likewise, to decipher the immunological molecular mechanisms related to smell involved in the development of neurodegenerative diseases.

Specifically, the two most prevalent neurodegenerative diseases have been addressed, which are Parkinson's disease and Alzheimer's disease. Comprehensive biochemical, olfactory, immunological, cognitive and imaging studies have been carried out in more than 300 patients, in order to verify the relationship between smell, the immune system and cognition of the participants. 

This connection has also been investigated through the use of an immunostimulating odorant such as menthol, analysing its impact on the immune system and cognitive ability in animal models. It has been observed that short and repeated exposures to the menthol aroma regulate the immune response in mice and significantly improves their cognitive ability, demonstrating how it is possible to modulate brain activity through the olfactory pathway.

On the other hand, the Navarrabiomed research units of Clinical Neuroproteomics and Geriatrics have launched, in collaboration with the University Hospital of Navarra, a study to examine the effects of controlled and supervised olfactory training on olfactory function, in older people, and to better understand the relationship between smell, the immune system and brain function in aging. When subjecting older people to olfactory training, it has been proven that repeated exposure to odorants leads to increased olfactory sensitivity. It is a non-invasive technique without significant side effects that has proven effective in some patients with olfactory dysfunction.

The INNOLFACT project has generated a database with information associated with more than 250 variables that will be analysed in a second phase of development with artificial intelligence and machine learning technology, with the aim of generating predictive algorithms of clinical impact.

Research with a gender perspective

It is known that diseases associated with aging, such as Alzheimer's disease and Parkinson's disease, occur differently in men and women, among other reasons, due to differences in genetic risk factors, the immune system and the progression of the pathology itself. The INNOLFACT consortium has demonstrated how olfactory metabolism differs between men and women with Alzheimer's or Parkinson's, identifying, using olfactory proteomics techniques, hundreds of proteins with differential behaviour between sexes. This information is essential, in order to establish a precision olfactory medicine without gender bias, with personalized diagnoses and treatments beneficial for the whole of society.

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Reunión final del proyecto estratégico INNOLFACT, presidida por la directora general de Industria, Energía y Proyectos Estratégicos S4 Uxue Itoiz
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Integrantes del consorcio del proyecto INNOLFACT junto con personal técnico de Gobierno de Navarra durante la visita final de proyecto.
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INNOLFACT - Implementación de la Medicina de Precisión Olfatoria
Enrique
Santamaría Martínez
Head of the Unit

Irene Lasheras Otero will defend her doctoral thesis on Wednesday, June 28th

Author
Navarrabiomed

Irene Lasheras Otero, a predoctoral researcher at the Cancer Signaling Research Unit of Navarrabiomed-IdiSNA, will present her doctoral thesis at the Public University of Navarra on Wednesday, June 28th, at 11:00 a.m. in the Navarrabiomed auditorium. The thesis, entitled “Metabolic Regulation of Anoikis and Implications in Melanoma Metastasis” has been conducted at Navarrabiomed under the supervision of Dr. Imanol Arozarena Martinicorena, Principal Investigator of the Cancer Signaling Research Unit at Navarrabiomed. Irene’s research aims to identify relevant mechanisms in the survival of circulating melanoma tumor cells.

Research Development and Results

Melanoma is a type of skin cancer with a special capacity to produce metastases, which cause 90% of cancer-related deaths. Metastases originate from tumor cells that leave the primary tumor, enter the bloodstream, and spread throughout the body.
Circulating tumor cells are the key link between a primary tumor and distant metastases. Generally, in the bloodstream, the loss of adhesion of circulating tumor cells leads to cell death (anoikis), therefore these cells must develop resistance to anoikis in order to later colonize organs such as the lungs, liver, or brain.

During her doctoral thesis, Irene has focused on analyzing these resistance mechanisms via RNA sequencing analysis. The results obtained demonstrate that both suspended melanoma cells and circulating melanoma tumor cells reconfigure lipid metabolism by inducing fatty acid (FA) transport and genes related to FA beta-oxidation. In melanoma patients, the high expression of FA transporters and FA beta-oxidation enzymes significantly correlates with lower overall survival and progression-free survival.

Furthermore, the findings reveal that carnitine transferases, specifically octanoyl transferase and acetyl transferase, are some of the most highly expressed regulators in circulating melanoma tumor cells. These proteins control the transport of medium-chain FAs produced in the peroxisome to the mitochondria to fuel mitochondrial beta-oxidation. Inhibition of octanoyl transferase or acetyl transferase, and short-term treatment with thioridazine or ranolazine (inhibitors of peroxisomal and mitochondrial FA beta-oxidation, respectively), suppressed melanoma metastasis formation in mice.

Moreover, to gain a more comprehensive understanding of the metabolic mechanisms that regulate anoikis resistance, a study was conducted using CRISPR-Cas9, which identified the mitochondrial electron-transport chain and cholesterol metabolism as potential mediators of anoikis resistance in melanoma.


Funding and Dissemination of Results
This research has been funded by the Carlos III Health Institute and the Navarrabiomed 2019 predoctoral grant program. Additionally, in 2022, Irene conducted a six-month stay in Dr. James Olzmann’s laboratory at the University of California, Berkeley, thanks to a travel fellowship from the European Association for Cancer Research (EACR).

The work conducted has resulted in a scientific publication, in February 2023, in the Journal of Investigative Dermatology, entitled “The Regulators of Peroxisomal Acyl-Carnitine Shuttle CROT and CRAT Promote Metastasis in Melanoma.”

Furthermore, the results have been disseminated at various scientific conferences, including the UCSF-UCB Liver Metabolism Symposium in Berkeley, California, in 2020, and the Seed and Soil: Mechanism of Metastasis conference organized by the EACR in Berlin.
 

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Irene Lasheras Otero, investigadora predoctoral de la Unidad de investigación de Señalización en Cáncer de Navarrabiomed-IdiSNA
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Navarrabiomed leads a multicenter study that could increase the efficacy of immune checkpoint blockade therapies in lung cancer

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Navarrabiomed
  • Fractalkine was identified as a key biomarker associated to clinical response to immune checkpoint blockade therapy which could improve its efficacy in one of the four most frequent types of cancer


Navarrabiomed carried out a study in which the status of the immune system was evaluated in lung cancer patients before and during immunotherapy. The study showed that the quantities and diversity of immune cells (myeloid cells) in blood from patients who responded to immunotherapies was comparable to that of healthy individuals. Moreover, the researchers found that elevated concentrations of fractalkine were found in these patients. Fractalkine is a protein required for maintaining an active, functional immune system. These findings could lead to the development of new treatments and more efficacious immunotherapies by using this protein in conjunction with current therapies. 

The results were published in the journal EMBO Reports. The project was coordinated by Dr. Ana Bocanegra and Dr. Grazyna Kochan, researchers at the Onco-Immunology Unit of Navarrabiomed headed by Dr. David Escors. The study was carried out in close collaboration with the department of Medical Oncology at Hospital Universitario de Navarra (HUN) led by Dr. Ruth Vera, and it was funded by grants from the Spanish Association Against Cancer, Carlos III Health Institute-ERDF and the Government of Navarra’s Ministry of Economic and Business Development. 
 

Research development 

The study identified fractalkine as a biomarker of response by associating elevated concentrations of the protein with a better response to immune checkpoint blockade therapies. This protein was also presented as a new therapeutic agent capable of increasing the efficacy of PD-1 immune checkpoint blockade therapies in animal models of lung cancer that were previously resistant to this therapy. 

The authors reported that therapies that are more efficacious could be developed from these results in the medium/long term by using fractalkine to stimulate immunoreactivity and thus improve the response to immunotherapy. 

“These results confirm the need for a functional immune system prior to the administration of immunotherapies and, most importantly, they open up a line of research in which the anti-tumor action of fractalkine can be enhanced. In the long term, fractalkine treatment in combination with immunotherapies could be assessed in clinical trials,” said Navarrabiomed researcher Grazyna Kochan. 
 

Collaborative study

The research team from Navarrabiomed and HUN collaborated with multidisciplinary groups from Navarra, La Rioja and Madrid coordinated by professionals with a proven track record in cancer research and clinical care, including: Dr. Rubén Pío, Dr. Luis Montuenga and Dr. Juan José Lasarte from Cima Universidad de Navarra, Dr. Alejandra Roncero from Hospital Universitario San Pedro (Logroño, La Rioja), Dr. Carolina Gotera from Hospital Universitario Fundación Jiménez Díaz (Madrid), Dr. Alfonso Ventura from Centro de Salud Salazar-Ezcároz (Navarra) and Dr. José Pichel from Centro de Investigación Biomédica de La Rioja (CIBIR, Logroño). Patients and their family members at the HUN and residents in Centro de Salud Salazar-Ezcároz (Navarra) also participated in the study.


Caption > From left to right: Luis Montuenga (Cima), David Escors and Grazyna Kochan (Navarrabiomed), Ruth Vera (HUN) y Rubén Pío (Cima). Absent in the photo: Ana Bocanegra (Navarrabiomed).

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From left to right: Luis Montuenga (Cima), David Escors and Grazyna Kochan (Navarrabiomed), Ruth Vera (HUN) and Rubén Pío (Cima).
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Researchers from HUN and Navarrabiomed identify two proteins to improve the diagnosis of ALS

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Navarrabiomed
  • Tomorrow marks World ALS Day, a disease that currently affects about 50 people in Navarra.

The University Hospital of Navarra (HUN) and the biomedical research center Navarrabiomed have identified two proteins, namely sTREM2 and pTDP43, as potential blood biomarkers that will improve the diagnosis of Amyotrophic Lateral Sclerosis (ALS). The results, stemming from the collaboration between both centers since 2013 to investigate this disease, have recently been published in the journal Brain, Behavior and Immunity.

ALS is a degenerative disease of the motor neurons, which control voluntary muscle movement, and primarily affects adults. This Wednesday commemorates the World Day for this condition, which currently affects about 50 people in Navarra.

The study, which was made possible by funding from the “la Caixa” Foundation, the Luzón Foundation, and the Navarra ALS Association (ANELA), involved professionals from the Motor Neuron Diseases Research Group at HUN, led by Dr. Ivonne Jericó Pascual, and the NeuroEpigenetics Unit at Navarrabiomed, led by Dr. Maite Mendioroz Iriarte.

The research has been carried out with the voluntary participation of patients and healthy individuals recruited by the Multidisciplinary Motor Neuron Unit at HUN. Post-mortem neurological tissue samples from the Navarrabiomed Biobank, from individuals who granted consent during their lifetime to support research, have also been incorporated.
 

Research Details  

Neuroinflammation, or inflammation of the nervous system, is implicated in the development of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and ALS. In this context, the HUN and Navarrabiomed team has identified TREM2 as one of the key genes involved in this process. Specifically, they have identified a significant increase in TREM2 expression in the spinal cord. They have also observed an increase in the soluble fraction of this protein (sTREM2) in the cerebrospinal fluid and blood of ALS patients.

Since TREM2 is a nonspecific marker for neuroinflammation, and not specifically for ALS, the team has also analyzed the levels of the protein pTDP43, one of the main neuronal markers directly associated with ALS.

Dr. Jericó emphasizes the relevance of the research: “The relationship between pTDP43 and sTREM2 allows us to identify the molecular fingerprints of ALS in each patient, which is promising for advancing towards new therapeutic targets. In fact, clinical trials with patients are already underway in other neurodegenerative diseases, such as Alzheimer’s, to modify the action of TREM2.”

Photo: Researchers Maite Mendioroz and Ivonne Jericó at Navarrabiomed.
 

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La investigadoras Maite Mendioroz e Ivonne Jericó en Navarrabiomed.
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