Unidad de Investigación

• The Carlos III Health Institute finances two projects in Navarre through Spain's COVID-19 Fund and grants the full amount applied for in both cases. 

The Spanish Ministry of Science and Innovation, through the Carlos III Health Institute (ISCIII), has awarded €232,000 to develop two public research projects within the context of the Navarre Health Research Institute (IdiSNA). David Escors Murugarren, a researcher at Navarrabiomed, and Jesús Castilla Catalán, a researcher at the Institute of Public and Occupational Health of Navarre (ISPLN), have received 100% of the amounts they applied for from the COVID-19 Fund, a mechanism approved by Royal Decree-Law 8 of 17 March 2020 on urgent extraordinary measures for dealing with the economic and social impact of COVID-19.

David Escors, the principal investigator at the Navarrabiomed Oncoimmunology Research Unit, began his scientific career working on coronaviruses at the Spanish National Biotechnology Center (CNB-CSIC), along with researcher Luis Enjuanes. He then continued his work at University College London (UCL) by applying lentiviral vectors and gene therapy in immunotherapy. He is a coronavirus specialist and the positive evaluation received from the ISCIII will enable him to obtain the €115,000 he applied for to develop the project “Platforms for developing biosafe SARS-CoV-2 vaccines.”

The aim of the initiative is to develop a platform for engineering biosafe vaccines for the virus that causes COVID-19 disease. The focus will be on the expression of viral proteins that may activate immunity. This line of research was started up specifically for COVID-19, given the current health emergency, but is based on the European ISOLDA Project - Horizon 2020 for generating more effective and safer virus vaccines (yellow fever, influenza and coronavirus) for adults over 65. Navarrabiomed has worked on this project since 2019 in coordination with professionals from the Spanish National Research Council (CSIC) and with Dutch, German and Italian collaborators.

Institute of Public and Occupational Health of Navarre

At the Institute of Public and Occupational Health of Navarre’s Group of Infectious Diseases and Vaccines, Jesús Castilla will lead the study “Infection, Hospitalization, ICU Admissions and Deaths Caused by SARS-CoV-2 in a Population Cohort.” To carry out the study, he will also receive the total amount applied for from the ISCIII: €117,000.

His proposal focuses on estimating the effect of sociodemographic characteristics, chronic diseases and other conditioning health factors on the risk of infection, hospitalization and severe forms of COVID-19. This will involve calculating the incidence of suspected cases, infections confirmed using PCR, hospitalizations, ICU admissions, assisted ventilation and mortality. The mortality rate will also be calculated in confirmed cases and hospitalizations. Antibody seroprevalence will also be evaluated in a sample of patients from the sentinel physician network and/or donors.

This is the second SARS-CoV-2 initiative for Jesús Castilla, given the ISPLN’s participation in the European project I-MOVE-COVID-19, with the involvement of 11 countries and 20 organizations. It is one of the European projects funded through the fast-track call of Horizon 2020, the European Union’s research and innovation program to promote research of different aspects of the SARS-CoV-2 virus.

Both research projects financed by the ISCIII will form part of the scientific activity of the IdiSNA, a public-private partnership for promoting biomedical research in Navarre. Both the ISPLN and Navarrabiomed are partnership members.

El Dr. Hugo Arasanz, oncólogo del Complejo Hospitalario de Navarra e investigador de la Unidad de Inmunomodulación de Navarrabiomed - IdiSNA, recibió ayer en Madrid la Ayuda Clínico Junior de la Asociación Española Contra el Cáncer (AECC). La financiación recibida (120.000 €) se destinará al proyecto "Subpoblaciones linfocitarias como biomarcador predictivo de respuesta a inmunoterapia anti-PD1/PDL1 en carcinoma no-microcítico de pulmón avanzado en 1º línea de tratamiento". Este estudio se desarrollará durante los próximos cuatro años y contará con la dirección del Dr. David Escors. 

El Museo Reina Sofía acogió ayer la entrega de las ayudas anuales de la AECC, dentro de los actos programados en el Día Mundial de la Investigación en Cáncer (WCRD en sus siglas en inglés), que se comemora cada año el 24 de septiembre. En total, la AECC ha entregado casi 21 millones de euros para financiar 171 proyectos que se suman a los 56M€ con los que hoy se están financiando 380 proyectos de investigación en desarrollo.

Asimismo, la asociación ha puesto de manifiesto la necesidad de elaborar un Plan Nacional de Investigación en Cáncer para alcanzar el 70% de supervivencia media a cinco años en el año 2030, en la actualidad se sitúa en un 53%.

Más información sobre el proyecto

La inmunoterapia antiPD1/PDL1 ha supuesto una revolución en el tratamiento del cáncer no-microcítico de pulmón, ya que ha mejorado los resultados de la quimioterapia, asociando además menor toxicidad. Por desgracia la proporción de pacientes que responden al tratamiento es reducida, son menos todavía los que mantienen la enfermedad controlada durante un periodo de tiempo prolongado, y no se dispone de biomarcadores predictivos que permitan identificar a estos pacientes con precisión.

El equipo del Dr. David Escors ha desarrollado un sistema de monitorización de poblaciones linfocitarias por citometría de flujo a partir de sangre periférica en pacientes en progresión a quimioterapia que permite predecir aquellos que van a responder a la inmunoterapia. Dada la reciente aprobación de la inmunoterapia en pacientes en primera línea, este proyecto pretende correlacionar los perfiles linfocitarios de los pacientes y su dinámica con la eficacia del tratamiento en este contexto, incorporando además el estudio de las citosinas proinmunogénicas en plasma y la posible influencia del daño genotóxico en las células inmunitarias producido por las diferentes terapias como causa de menor eficacia en segunda línea.

El proyecto del Dr. Hugo Arasanz se completará con estudios mecanísticos in vitro que permitan conocer los elementos que condicionan la respuesta al tratamiento y plantear combinaciones que puedan revertir la resistencia primaria a estas terapias.

Experts gathered at the Public University of Navarra (UPNA) have urged health and sports professionals to become ‘health agents’ by promoting physical activity among young people and pregnant women. Their goal is to improve the health and fitness of the population as a strategy to prevent non-communicable chronic diseases like obesity, heart disease or type 2 diabetes. A symposium was held by UPNA in Pamplona on Thursday 9 May to discuss exercise prescription as a way to improve health in all ages. Organised by the School of Medical Sciences and the Department of Medical Sciences, the event drew some 130 sports, health and biomedical experts.

Two UPNA researchers, who are also members of Navarrabiomed (the joint biomedical research centre of the Government of Navarra and the Public University of Navarra) and the Navarra Medical Research Institute (IdiSNA), delivered speeches: Mikel Izquierdo Redín, organiser the event, and Robinson Ramírez-Vélez. Mikel Izquierdo talked about strength training and the functions of the muscular system, ‘which a number of health professionals consider important for improving health and recovering from diseases linked with a sedentary lifestyle and population ageing, as well as for optimising sport performance after muscle injury.’ He debunked some of the myths created by pseudo-therapies in connection with strength training and improved muscle function. He said that muscle loss is not an inevitable outcome of ageing, as it can be prevented with proper training. He also observed that it is not true that children cannot do strength training exercises; on the contrary, they can, as long as they engage in controlled movements that are suitable for their age. He insisted that fitness ‘always’ offers benefits to patients who suffer from diseases such as type 2 diabetes and denied that the best muscle training is the one associated with extreme fatigue.

Finally, Izquierdo questioned the effectiveness and validity of the Kinesio Taping Method (which consists in applying elastic strips on muscles to treat pain), hypopressive techniques, electro stimulation suits and muscle roller sticks.

Health and pregnancy

Robinson Ramírez-Vélez said that, despite the efforts made to prevent non-communicable chronic disease, such as promoting healthy habits like physical exercise, a balanced diet, a good night’s sleep, quitting smoking and drinking, and so on, ‘we have failed to obtain the desired results.’ Studies reveal, he added, that ‘the mother’s state of health during pregnancy conditions to some extent the developing baby’s health later in life.’ He highlighted the importance of physical activity in children and adolescents – both aerobic exercise and resistance/strength training. Also, he insisted that health professionals should prescribe physical activity in all stages of life, even pregnancy.

The closing lecture was delivered by Antonio García-Hermoso, of Navarrabiomed and IdiSNA. He showed his disappointment in the fact that ‘Physical Education in school is not considered to be as important as subjects.’ He cited important international studies concluding that ‘exercise in youth is good for both physical and mental wellbeing.’ Finally, García-Hermoso recommended that ‘sports should be given the importance they deserve in primary, secondary and higher education.’

The Microbial Pathogenesis Unit of Navarrabiomed-Public University of Navarra (UPNA) has found a new genetic organisation in bacteria that helps better understand bacterial biology. The study of this genetic architecture was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Research background

In 1961, François Jacob and Jacques Monod discovered that bacteria group the genes that encode the proteins for a certain metabolic pathway in a single transcription unit (which they called ‘operon’). They won the Nobel Prize in Physiology or Medicine in 1965 for their discovery.

The bacteria they chose for their study was Escherichia coli, which normally lives in the intestines of healthy people; specifically, they studied the set of genes E. coli bacteria need to transport lactose (milk sugar) and break it down. E. coli only produces the three proteins it needs to digest lactose when the sugar is available. To simplify transcription regulation, the three genes involved are adjacent in the genome and under a single regulation system. Similar transcriptional regulation systems are found in other metabolic pathways in all bacteria.

Research at Navarrabiomed

In 2018, the team of researchers at Navarrabiomed coordinated by Iñigo Lasa Uzcudun, Head of the Microbial Pathogenesis Unit and Director of the biomedical research centre, described a new way genes are organised in bacteria. This regulation system has a higher level of regulation in operon structure, which the authors of the study named ‘non-contiguous operon’.

The bacterial model analysed has a group of four genes that are transcribed as a transcription unit despite the existence of a separate gene between the second and third genes that is transcribed in the opposite direction.

This transcriptional architecture results in an antisense transcript that acts as a mutual regulation system for the expression of the genes in the operon and the gene that produces this antisense transcript. Therefore, the concept of non-contiguous operon includes not only the genes transcribed from the same transcription unit but also overlapping genes whose expression is coordinated with that of the genes in the operon.

This finding deepens the understanding of bacterial biology and may trigger novel developments in the fields of synthetic biology and bacterial biotechnology.
The study was carried out as part of the scientific activity done at the Navarra Medical Research Institute (IdiSNA).

• Paper published in PNAS.

• El estudio, financiado por el Ministerio de Economía, ha sido publicado por la prestigiosa revista Nature Communication.

Un equipo científico del centro de investigación biomédica Navarrabiomed -centro mixto del Gobierno de Navarra y la Universidad Pública de Navarra (UPNA)- ha conseguido caracterizar el sistema sensorial que las bacterias utilizan entre otras cosas para multiplicarse en el cuerpo humano y causar infección.

El avance, que ha sido publicado por la revista científica Nature Communications y cuenta con financiación del Ministerio de Economía, Industria y Competitividad, permite comprender mejor cómo las bacterias se adaptan a las diferentes condiciones ambientales y posibilitará el desarrollo de antibióticos más específicos y eficaces.
El estudio ha contado con el liderazgo del doctor Iñigo Lasa, director de Navarrabiomed e investigador responsable del Grupo de Patogénesis Microbiana del centro. Asimismo, han colaborado investigadores del Instituto de Agrobiotecnología (UPNA-CSIC-Gobierno de Navarra), del Instituto de Biomedicina de Valencia (CSIC) y del Institute of Infection, Immunity and Inflammation, University of Glasgow.

Bacterias superresistentes

Actualmente, la aparición de bacterias farmacorresistentes, que no responden a tratamientos con antibióticos, constituye uno de los problemas sanitarios a escala mundial priorizados por la Organización Mundial de la Salud (OMS).

Las bacterias detectan, responden y se adaptan a los cambios en su entorno utilizando unos elementos sensoriales denominados sistemas de dos componentes. Este tipo de sistemas sensoriales están presentes en bacterias, hongos y plantas, pero no se encuentran en células animales. En el caso de las bacterias, regulan procesos celulares tan importantes como la virulencia o su propio crecimiento, lo que los convierte en dianas para el diseño de nuevas terapias antimicrobianas.

El objetivo del trabajo ha consistido en eliminar todos los sistemas de dos componentes, es decir el sistema sensorial completo, en Staphylococcus aureus, uno de los principales patógenos humanos según la OMS y, posteriormente, en la generación de una colección de bacterias cada una de las cuales contiene un único sistema de dos-componentes. Esta estrategia ha permitido simplificar una compleja red sensorial en cada uno de sus elementos para comprender cuál es la función individual de cada uno de los sistemas y la relación existente entre ellos. 

Aplicación clínica de la investigación

En relación a la aplicación clínica, Iñigo Lasa apunta al desarrollo de nuevos antibióticos más específicos. “El hecho de que los sistemas de dos componentes estén presentes en todas las bacterias patógenas y no en las células de nuestro organismo nos puede permitir desarrollar fármacos que bloqueen estos sistemas, evitando así el desarrollo de la bacteria durante la infección, sin causar ningún efecto secundario sobre nuestras células”.

En este sentido, las bacterias generadas en este estudio han sido patentadas y actualmente el equipo analiza diversos compuestos marinos que puedan incorporarse en el tratamiento y control de infecciones en la práctica clínica.

La investigación forma parte de la actividad científica del Instituto de Investigación Sanitaria de Navarra (IdiSNA), agrupación público-privada para el fomento de la investigación biomédica en la Comunidad Foral y de la que son miembros Navarrabiomed y la UPNA.

• Información adicional sobre el paper: Behind the paper - Nature Microbiology: "Life without sensing. Can Staphylococcus aureus live without two-component sensorial system?"

• JAMA Pediatrics, the journal of the American Pediatrics Association, has published the study results.

A group of researchers from Navarrabiomed and the Department of Health Sciences at the Universidad Pública de Navarra (UPNA) specializing in prescribing physical exercise to improve health and quality of life has published an article on the effects of increasing the quality and quantity of physical education (PE) classes on improving the health-related physical fitness and fundamental motor skills of young people (ages 3 to 18). The article was recently published in JAMA Pediatrics (Journal of the American Medical Association).

The study analyzed data from approximately 50,000 young people and concluded that qualitative strategies such as including games and activities involving a high level of cardiovascular and muscular work, as well as better methodological session planning could provide young people with healthy benefits in terms of fitness and fundamental motor skills.

In addition to Antonio García-Hermoso, Robinson Ramírez-Vélez, Alicia María Alonso-Martínez and Mikel Izquierdo Redín (who form part of Navarrabiomed, Idisna and UPNA), the article authors also include Miguel Ángel Pérez-Sousa (Universidad de Huelva) and Rodrigo Ramírez-Campillo (Universidad de Los Lagos, Osorno, Chile).

Exercise is necessary to improve physical fitness

The study researchers also point out that it is not always possible to increase the number of hours spent per week on exercise or PE classes during school hours and therefore recommend improving the efficiency of these sessions by using strategies such as high-intensity interval training (HIIT), and muscle strength, jumping or circuit training. However, the authors mention that, despite the benefits of these strategies during school hours, young people should also participate in more out-of-school physical activities based on their age group (i.e., 60 minutes a day of moderate to intense physical activity).

They argue that PE classes also offer other benefits not specifically related to physical activity, such as helping young people develop socialization, teamwork and body language skills, and fostering healthy habits. Above all, the authors highlight the fact that improving physical fitness among school kids is a fundamental short- and long-term aspect of good health, given the high rates of obesity and physical inactivity among young people, which the authors refer to as “a public health problem that must be addressed by schools.”

Researchers from the Public University of Navarra (UPNA), Navarrabiomed and the Education Department of the Government of Navarra participated in a research project financed by the Navarra Education Department to create the first Physical Education Observatory for 3- to 6-year-old children in Navarra. They were Alicia Alonso, Mikel Izquierdo and Alazne Antón (UPNA), Antonio García-Hermoso and Robinson Ramírez-Vélez (Navarrabiomed), and Berta Villoslada and Berta Echavarri (CIP FP Lumbier-Education Department, Government of Navarra).

The Observatory is meant to promote physical activity in schoolchildren, reducing their screen time and adding relaxation time instead, as it has been shown that developing healthy habits in childhood is crucial to preventing cardiovascular disease in adult life. In order to achieve its goal, the Observatory will conduct a series of assessments in local schools, with children and their families, testing their fitness, measuring their sleep time and analysing all this information with them. The evaluation includes physical tests (jumping with both feet, speed/agility tests, etc.), body composition analysis (waist circumference, percentage of body fat and body mass index) and the use of personal electronic devices to measure the intensity of everyday activity and rest/sleep periods. In addition, the correlation will be established between fitness and school achievements.

The study is set to begin in Colegio Santa María la Real-Maristas Pamplona in October, then moving to Colegio Público San Juan de la Cadena. Finally, there will be a special teacher training module in CIP FP Lumbier, targeted at the students in the higher education training cycles (80), who will become assessors. This will be part of the module titled ‘Fitness testing and response to accidents’.

Throughout the process, school teachers will participate in measurements and evaluations, in an effort to introduce new trends, methods and formulas in children health assessment. According to the authors of the study, ‘the results might help understand why schoolchildren are gaining weight and their performance at school is worsening, with low levels of physical activity.’

Childhood as a critical period to develop healthy habits

‘Early childhood is a critical period for physical, social and cognitive development, to establish healthy behaviour patterns that can be kept into adulthood,’ the researchers say. Studies show that ‘regular participation in physical activities by pre-schoolers is essential for normal development and growth, with immediate and long-term benefits for physical and psychological wellbeing,’ they add. However, they explain, evidence for this age group is still relatively scarce as compared to the data available for children and adolescents aged 6 to 17.

Recently, the World Health Organisation (WHO) published new guidelines on physical activity, sedentary behaviour and sleep for children under 5 years of age. According to these recommendations, children 3-5 years of age should spend at least 180 minutes in a variety of types of physical activities, of which at least 60 minutes is moderate- to vigorous-intensity activity. ‘Despite the benefits for health of regular physical activity, many pre-schoolers fail to meet these standards,’ the authors of the study state. The Observatory is aimed at improving results in this area.

The predoctoral researcher of the Neuroepigenetics Unit of Navarrabiomed, Amaya Urdánoz Casado, will be sitting her viva from the Public University of Navarra next Tuesday, July 5th at 11:00 in the Assembly Hall of Navarrabiomed.

The doctoral work, entitled "Identification of circRNAs as candidate epigenetic biomarkers in Alzheimer's disease”, has been developed at Navarrabiomed under the direction of Maite Mendioroz Iriarte and Idoia Blanco Luquin.

This research focuses on Alzheimer's disease (AD), a neurodegenerative, chronic and, at the moment, irreversible disease that represents the first cause of age-related dementia. It is postulated that circular RNAs (circRNAs) play important roles in brain homeostasis, as well as in the development of neurodegenerative diseases. 
The objective of this doctoral thesis is to identify, in patients with AD compared to controls, circRNAs with differential expression in the human entorhinal cortex (CE), a brain region especially vulnerable to AD. To do this, the study of the expression of circRNAs is proposed using a candidate gene and a genome-wide approach.
In the former, candidate gene approach, 10 genes were selected, whose role in AD had already been described in the literature and from which circRNAs originated. 6 circRNAs derived from the APP, ADAM10, CDR1 and HOMER1 genes were identified, of which 4 showed a differential expression in EC between patients with AD and controls. In addition, three potential circRNAs derived from the TREM2 gene were identified for the first time in the EC.

In the second genome-wide approach, new circRNAs differentially expressed in the EC were identified that so far had not been associated with the development of the disease by transcriptome sequencing in patients with AD with respect to controls. In addition, several circRNA-miRNA-mRNA interaction networks (competitive endogenous RNA network, ceRNET) were predicted.
The results obtained show the deregulation of a series of circRNAs in the EC affected by AD with respect to controls, suggesting their potential involvement in the pathogenesis of the disease.

Disclosure of results and financing

The work carried out has resulted in a scientific publication in the International Journal of Molecular Sciences, “Gender-Dependent Deregulation of Linear and Circular RNA Variants of HOMER1 in the Entorhinal Cortex of Alzheimer's Disease”.
In addition, it has been disseminated at several national and international congresses, the Alzheimer's Association International virtual Conference Satellite Symposium, the 15th International virtual Conference on Alzheimer's and Parkinson's Diseases: Mechanisms, Clinical Strategies and promising Treatments of Neurodegenerative Diseases or at the BraYn Conference: Second brainstorming research assembly for young neuroscientists.

For the development of the thesis, Amaya Urdánoz has received several grants for the recruitment of doctoral students by companies and research and knowledge dissemination organizations: industrial doctoral students 2018-2020 and grants for the financing of a predoctoral contract in health sciences and technologies in the period 2019-2022, both funded by the Government of Navarra. She also received an Erasmus scholarship for her stay at Karolinska Intitutet and an aid for the mobility of doctoral students - UPNA Congresses (2021) to attend, with a communication of her research, the 15th International virtual Conference on Alzheimer's and Parkinson's Diseases: Mechanisms, Clinical Strategies and promising Treatments of Neurodegenerative Disease.

• The programme will offer support to the development of studies in digestive medicine, geriatrics, neuroscience and oncology that will bring advancement and excellence in these fields of research.
• ‘la Caixa’ Foundation and Caja Navarra Foundation are channelling 1.2 million Euro into this programme, to be run by the biomedical research centre Navarrabiomed, where four doctors from the Navarra Health System-Osasunbidea (SNS-O) will carry out quality biomedical research studies.
• Through this programme, ‘la Caixa’ Foundation and Caja Navarra Foundation will give support to the leading research centres in Navarra during the 2017-2021 period. Universities and research centres will thus get a total 6.4 million Euro.

Ana Díez Fontana, Regional Director of CaixaBank in Navarra; Javier Miranda, Chairman of Caja Navarra Foundation; and Iñigo Lasa, Director of Navarrabiomed, announced the research lines to be developed by doctors Eduardo Albéniz Arbizu, Nicolás Martínez Velilla, Maite Mendióroz Iriarte and Antonio Viudez Berral, who were selected by an external evaluation committee from 12 candidates.

The specialists in the programme will be relieved from part of their medical activity so that they can do research. They need time to develop their scientific projects and produce new knowledge in their medical specialties. The initiative enables the establishment of a critical mass of professionals that combine medical activity with research jobs, thus promoting translational medicine to the benefit of patients and society as a whole.

The four doctors selected to join the programme will soon start working at the labs of Navarrabiomed – the joint biomedical research centre of the Government of Navarra and the Public University of Navarra (UPNA). They will establish separate research units for the development of their projects, based on clinical practice at the Navarra Hospital Complex (CHN), with support from other Navarrabiomed units and platforms.

In addition to streamlining research activities in the respective units, they will encourage the participation of resident medical interns (MIRs) by getting them involved in biomedical research projects, trials and programmes.

Four excellent research projects in digestive medicine, geriatrics, neuroscience and oncology

Eduardo Albéniz Arbizu has worked in a number of hospitals across Spain. He received training in advanced endoscopy in France, Japan and China. Currently, he is working at the Gastrointestinal Endoscopy Unit of the CHN Digestive Medicine Service.

Dr Albéniz specialises in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for the removal of early-stage gastrointestinal tumours. These advanced procedures reduce the number of surgical and other more invasive interventions in the treatment of superficial neoplastic lesions. Resection of colorectal polyps, for example, is the procedure with the highest survival rates observed in screening studies for colorectal cancer carried out in Navarra.
The goal of the project led by Dr Albéniz is to provide evidence for the identification of predicting factors for the effectiveness of resection procedures and other factors associated with potential complications that might be minimised.

Nicolás Martínez Velilla has been the Head of the Geriatrics Unit at CHN since 2015. In 2013, he was appointed head of a team partnered with Navarrabiomed for the promotion of research into different aspects of geriatric medicine.

Dr Martínez Velilla’s proposal includes a thorough study for the prevention of old-age frailty and disability or dependency in hospitals and in the community at large. Furthermore, it includes the creation of a European cross-border network to deal with various aspects of ageing. The project is aimed at rethinking hospitalisation of older adults, prescribing exercise to older patients in hospitals so as to improve their quality of life and increasing the sustainability of the health system.

Maite Mendióroz Iriarte has built her professional career as a doctor and researcher in Pamplona, Barcelona, San Sebastián and New York. Since 2010, she has been a member of the Neurology Department at CHN. Over the past few years, she has received grants from ‘la Caixa’ Foundation, Caja Navarra Foundation and the Government of Navarra to boost activity in the Neuroepigenetics Unit at Navarrabiomed.

Between 2018 and 2021, Mendióroz Iriarte will develop a project whose goal is to identify a potential blood-based epigenetic biomarker for early detection and treatment of Alzheimer’s disease. Her study might become the first step towards the implementation of precision medicine in neurodegenerative diseases.

Antonio Viudez Berral has developed his professional career in Navarra, Catalonia and Baltimore, USA. In 2010, he joined the Medical Oncology Service at CHN. Since then, he has been a researcher at Navarrabiomed as well.

Dr Viudez’s project will study pancreatic neuroendocrine tumours to find accurate markers that predict the effectiveness of certain therapies.

In addition, the Medical Oncology Service will be able to strengthen its scientific activity, establishing new lines of research for the improvement of diagnosis, prognosis and prediction of treatment response and toxicity.

From left to right: Luis Gabilondo, Ana Díez, Maite Mendióroz, Eduardo Albéniz, Antonio Viudez, Nicolás Martínez, Javier Miranda and Iñigo Lasa.

The Navarra Hospital Complex (CHN) and the biomedical research centre Navarrabiomed have carried out an innovative study of the so-called ‘liquid biopsy’ in amyotrophic lateral sclerosis (ALS) diagnosis and follow-up. The results of this study were published in the international peer-reviewed journal Annals of Translational Medicine.

On the occasion of the Global ALS Awareness Day, members of the multidisciplinary team treating patients with ALS in Navarra shared the latest research and care developments in connection with this disease, including this innovative study of the use of liquid biopsy testing in ALS diagnosis and follow-up.

The leaders of the study were Maite Mendióroz and Ivonne Jericó, doctors from the CHN Neurology Department and researchers at Navarrabiomed. The project was part of the scientific activity done at the Navarra Medical Research Institute (IdiSNA), a public-private agency for the promotion of biomedical research in Navarra. The survey involved ALS patients and a control group (individuals without ALS), and professionals from the departments of Neurology and Anaesthesiology and the Nursing Team at CHN, and the Neuroepigenetics Unit at Navarrabiomed.

According to the study coordinators, one of the biggest weaknesses in research into neurodegenerative disease is the difficulty to access and study the nervous tissue of living patients. In order to address this difficulty, the study analyses the application of liquid biopsy testing, a technique recently developed in the field of cancer research, to ALS diagnosis.

Liquid biopsy is based on the fact that, when cells degenerate and die, their contents – including DNA – flow into the bloodstream. The released DNA molecules contain biochemical information about the original cells (hence the name ‘biopsy’) – in this case, diseased neurons. The original cell contents can be isolated and analysed in blood samples (hence the name ‘liquid’). The researchers have successfully used this technique with ALS patients to identify a new gene, RHBDF2, as a biomarker for ALS diagnosis in the future.

‘To the best of our knowledge, this is the first time ever liquid biopsy has been used to diagnose neurodegenerative diseases. The results have been encouraging so far. Now we are planning to extend the technique to other neurodegenerative diseases, such as Alzheimer’s disease,’ the doctors said, adding that the survey was made possible by the generous participation of patients and their families, and the volunteers in the control group.

A multidisciplinary team, 11 years and more than 200 patients

The team treating ALS patients in Navarra have striven to promote ALS research right from the start. Currently, two researchers at the Navarrabiomed Neuromuscular Disease and Motor Neuron Disease Group (headed by Dr Jericó) are working on ALS for their PhD projects, and other four projects address this neurodegenerative disease – specifically, the identification of biomarkers for diagnosis and follow-up, the role of neuroinflammation, the underlying mechanisms, the analysis of genetic factors, and the study of epidemiological aspects and disability.
The Group coordinates both research and care activities, and collaborates with the Navarrabiomed Proteomics and Biobank platforms, the Neuroepigenetics Research Unit (headed by Dr Mendióroz) and the Navarra Public and Occupational Health Service (Rare Disease Registry).

Amyotrophic lateral sclerosis is a progressive nervous system disease with a heterogeneous clinical presentation but common symptoms like muscle weakness and progressive muscular atrophy. Prognosis is variable among patients. About 5 to 10 per cent of ALS is familial, which means it arises in families in which there is a history of ALS. The other 90 to 95 per cent of ALS is sporadic, meaning it occurs without a family history, its causes still being unknown. Every year, 1 to 2 people every 100,000 are diagnosed with ALS. Despite being a rare disease, it has a deep social and family impact. Currently, there is no cure for ALS, but this does not mean there is no treatment.

ALS care involves multiple disciplines. On the occasion of the Global ALS Awareness Day the multidisciplinary team at CHN shared an informative brochure with patients and their families, highlighting the importance of coordinated social and health care through multidisciplinary units or teams. Active for 11 years now, the CHN team have treated over 200 patients to date.

Navarra has been one of the first Spanish regions to implement a multidisciplinary care model for ALS patients. Since 2007, the region has been offering comprehensive, coordinated care to them and their families, through a multi- and interdisciplinary team whose members include a neurologist, (Dr Ivonne Jericó), a nutritionist (Dr Ana Zugasti), two pulmonologists (Dr Joan Boldú and Dr Begoña Fernandez), a neurophysiologist (Dr Asun Ibiricu), an intensive care physician (Dr Juan Pedro Tirapu), a social worker (Rakel Suescun), neurology nurses, dieticians, a palliative care service and members of the Psychological and Social Support Service at San Juan de Dios Hospital (Yolanda Santesteban and Ana Baños).

From the beginning, the team set out to offer adequate, tailored, patient-centred social and health care, while promoting research as the key to finding an effective treatment for ALS.
 

Image: Members of the multidisciplinary team treating patients with ALS in Navarra.

• Since 2015 the associations annual investment in research has been increased by 65%

On October 27th, 2019 Breast Cancer Association of Navarre SARAY collected 75,000 euros in the solidarity race celebrated in Pamplona. 49,970 euros will fund two studies developed by Navarrabiomed on metastatic breast cancer.

One of the projects is focused on liquid biopsy in this type of cancer, and it is led by Natalia Ramírez Huerto, the head of the Hematological Oncology Unit of Navarrabiomed. SARAY´s contribution for the second year of the project development raises to 24,970 euros. Other study lead by Cancer Signaling Unit head Imanol Arozarena Martinicorena will receive 22,000 euros. His project aims to develop new adjuvant therapies to treat brain and bone metastases from these tumors. The additional funds will be donated to the Chronos Hope Project from Solti Foundation.

On the 25th of June SARAY decided to allocate the incomes in a face-to-face and online assembly among 725 associates (event delayed three months later due to the COVID-19 crisis). During the last years, the organization shows a strong commitment with biomedical research performed in Navarre. Therefore, it is relevant to highlight that since 2015 SARAY has increased by 65% its annual investment in oncology research.

Imanol Arozarena, senior researcher from the Cancer Signalling Unit at the Navarrabiomed biomedical research centre and a member of Instituto de Investigación Sanitaria de Navarra (IdiSNA), has recently published a melanoma review with University of Manchester Professor Claudia Wellbrock.

The two scientists were asked by the renowned scientific journal Nature Reviews: Cancer to write an article on the latest findings in melanoma cell distinct phenotypes and their relevance for melanoma development and response to therapy.

As many as 4000 new melanoma cases are diagnosed in Spain every year. Malignant melanoma is a serious type of skin cancer that is usually metastatic. It is notorious for its intra- and inter-tumour heterogeneity.

Such variability results from the ability of melanoma cells (melanocytes) to adjust to changing environmental conditions by reprogramming their genetic expression. Thus, melanocytes develop resistance to both targeted therapy and immunotherapy, and their plasticity plays a role in metastasis development.

In their article, the authors reveal the importance of combining recent developments in genomic technologies and the availability of large gene expression datasets for a precise definition of the gene signatures that characterise changes in each patient’s tumours and the prognostic relevance for tumour development and response to therapy.

According to Arozarena, ‘By understanding the molecular mechanisms that adapt melanoma cells to anti-tumour drugs, we will be able to prevent both therapy resistance and the progression of metastatic melanoma.

• www.navarra.es
• Review Article - Phenotype plasticity as enabler of melanoma progression and therapy resistance