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• Four Catalan institutions are also participating in this project to develop molecules with coronavirus-neutralizing properties

The Supera COVID-19 Fund launched by Banco Santander through Santander Universities, in collaboration with Crue Spanish Universities and the Spanish National Research Council (CSIC), has granted €160,000 in funding to a research project on COVID-19 designed by a consortium made up of Navarrabiomed researchers and four Catalan institutions coordinated by the Universidad Pública de Navarra (UPNA). This project seeks to develop molecules with SARS-CoV-2-neutralizing properties for the treatment of patients requiring hospitalization and clinical supervision due to the infection’s severity.

These molecules are based on peptides specific to the ACE2 receptor that can reduce or halt the ability of SARS-CoV-2 to cause infection. “These molecules reproduce the human receptor region the virus attaches to,” explained project leader Jacinto López Sagaseta, from the Protein Crystallography Unit at the Navarrabiomed Biomedical Research Center. “We are trying to create molecules from this region that have a greater capacity to bind to the viral particle, which would hinder the virus’s ability to attach to the natural receptor and thus slow down infection.” According to López, these molecules may “help chemists design drugs that can mitigate the process and speed of infection and thereby facilitate patients’ clinical recovery”.

In order to implement the 12-month project, a consortium was set up of researchers from different disciplines, including chemical synthesis, protein engineering, structural analysis and cell biology, as well as specialists in the conditions of biosafety level three (BSL3, for laboratories, on a scale of one to four), to test the potential of these molecules. Specifically, besides Navarrabiomed and the UPNA, four Barcelona research institutions are also participating in the project: IRB Barcelona (Institute for Research in Biomedicine), IQAC-CSIC (Institute for Advanced Chemistry of Catalonia), CIBER-BBN (Bioengineering, Biomaterials and Nanomedicine Subject Area of the CIBER Biomedical Research Center), and IRTA (Institute of Agrifood Research and Technology). Besides Jacinto López Sagaseta, other Navarrabiomed researchers taking part in this research project include Gilda Dichiara Rodríguez, Elena Erausquin Arrondo and Ane Ochoa Echevarría, who are members of the Protein Crystallography Unit.
The consortium members hope that “the availability of molecules with a strong inhibitory effect will significantly mitigate the socioeconomic impact of the pandemic due to the persistence of current and/or future SARS-CoV-2 outbreaks, as well as outbreaks of other potentially harmful coronaviruses with similar entry routes,” said López.

€8.5 million fund

The €8.5 million Supera COVID-19 Fund has been earmarked for projects of different organizations that are based on the fund’s three-pronged strategic approach against COVID-19: research on the virus and its prevention, research on its social impact, and strengthening universities’ technological capacity and reducing the digital divide. A total of 700 grant applications were submitted, of which 35 were selected and received funding to the tune of €5 million to carry out applied research against the virus. Nearly €1 million was also distributed to twelve projects on the social impact of the virus. Finally, €2.5 million will be allocated to supply young university students in unfavorable socioeconomic situations throughout Spain with nearly 5,000 computers and 15,000 Internet connectivity solutions and webcams.

• The Government of Navarre provided €1.1 million in funding for eight research projects and has now added two more Navarre initiatives to the list of recipients of funding from the Carlos III Health Institute

María Chivite, the President of the Government of Navarre, recognized “the good work” being done at research centers and institutes in the Region of Navarre to find alternatives that help alleviate the effects of COVID-19. She spoke in the context of a meeting she attended this morning with ten researchers in charge of their own publicly funded studies on this disease, which has caused 515 deaths in Navarre and more than 27,000 in all of Spain.

The meeting was also attended by Santos Induráin, the Minister of Health, and Juan Cruz Cigudosa, the Minister of University, Innovation and Digital Transformation, and provided a firsthand opportunity to learn about the research purpose of the projects that have received grants from the Navarre COVI+D Fund. Created by the Government of Navarre to promote research on this topic, the fund paid out €1.1 million in May to eight projects that had received a favorable assessment from the Carlos III Health Institute. The Carlos III Health Institute has also provided direct funding of €232,000 for two other Navarre research projects.

Chivite took advantage of the forum to remind the participants of the Government of Navarre’s commitment to innovation and research “as a model of economic and social development,” not just through these grants, but also by means of the R&D&i Emergency Plan, presented last week, and the Reactivate Navarre Plan / Nafarroa Suspertu 2020-2023. The Government is also committed to improving technological infrastructure and promoting supra-regional cooperation. “We want Navarre to lead the way in biomedicine because we have the talent and skills to do just that. It’s one of the strategic areas we’re working on. We have to be able to transfer knowledge and research to favor industrial and technological development,” she said, before expressing her confidence that Navarre will become “a key stop on the R&D&i map.”

Chivite confirmed that the goal of the Government of Navarre is “to keep increasing investment and setting up strong pillars for the model of growth.” Navarre will thus be prepared for future challenges of the likes of COVID-19.

Chivite informed the researchers of the public support of their research work, though “people are aware of the pressure you’re under when you’re studying this coronavirus, because of the high expectations about finding a vaccine, treatments and other aspects that could alleviate the effects of a virus that has had a major impact on our society.” She asked for respect “for the time frames, rigor and meticulousness” of the researcher’s work, and also expressed hope that this work would promote “true and instructive information” that avoids fake news and disinformation in society as a whole.
 

Ten projects

In addition to President Chivite, the meeting was attended by Rosario Martínez, the Director General for Innovation. Also attending were the researchers from the ten projects that received public funding: Luis Martínez de Morentin, Fermín Mallor Giménez, Borja Sáez Ochoa, Natalia Ramírez Huerto, Jacinto López Sagaseta, Pablo Sarobe Ugarriza, Patricia Fanlo Mateo, David Escors Murugarren, Jesús Castilla Catalán and Leyre Ruete Ibarrola, who attended in representation of Beatriz Lacruz Escalada. They were joined by the heads of the different research centers where the projects are being carried out. This group included María Rosario Luquin, the Scientific Director of  the Navarre Health Research Institute (IdiSNA), Claudio Fernández, the Director of the Lurederra Foundation, and Íñigo Lasa Uzcudun, the Director of Navarrabiomed.

The directors of the ten research projects presented their lines of research, which include the study of possible vaccines, the use of specific drugs, resource management, the development of preventive measures and products, and the analysis of incidence bearing in mind sociodemographic characteristics and other conditioning factors.

The Government of Navarre aims to promote Navarre innovation and national prominence through the COVI+D Fund grants. But the goal is also to attract scientific talent, given the fact that these grants include staff payroll expenses.

High-cholesterol levels, or hypercholesterolemia, affects nearly 1500-2500 people in Navarra, and less than 20 per cent of them are not aware that they suffer from this condition. Hypercholesterolemia is considered to cause 22 per cent of coronary events, most of which could be prevented with early diagnosis and treatment. The biomedical research centre Navarrabiomed has launched NAGENCOL, a project to address this issue using whole-genome sequencing as a diagnostic tool to offer personalised treatment to patients who suffer from hypercholesterolemia. The project is framed within NAGEN, a global strategy aimed at applying genomic medicine in the Navarra Health System-Osasunbidea (SNS-O).

Currently, hypercholesterolemia poses a real challenge to the public health system, because the life expectancy of untreated patients can decrease by 25 years, and 50 per cent of them are more likely to have a heart attack before the age of 55. NAGENCOL addresses this problem, offering a new model that uses genomic information, together with other clinical and demographic data, to bring precision medicine to individual patients.

This ambitious public health project has a budget of 2 million Euro, contributed by the Department of Economic Development at the Directorate-General for Industry, Energy and Innovation of the Government of Navarra, within the framework of the Genomics and Advanced Medicine project (GEMA) and the Intelligent Specialisation Strategy S3.

The NAGENCOL activities are managed by five strategic partners specialising in clinical practice, scientific and technical services, and research. They include the Navarra Hospital Complex (CHN), Nasertic, Tracasa Instrumental SL and Navarrabiomed as the leader of the study. The project is headed by Dr Ander Ernaga and Dr Juan Pablo Martínez from the Endocrinology Service at CHN.

NAGEN Strategy

Since 2016, Navarrabiomed has been leading the Genomic Medicine Strategy (NAGEN) of the Navarra Health System-Osasunbidea. With the support of the Government of Navarra, Navarrabiomed has since coordinated two strategic projects: NAGEN 1000 (best precision medicine project award winner in 2018) and Pharmanagen.

The two initiatives, along with NAGENCOL, are being used to set up, in the SNS-O patient care units, the infrastructure required for using genomic data as a powerful diagnostic tool and to determine the best personalised treatment for each patient.

Navarrabiomed has led the NAGEN: Navarra Genome 1000 project since 2016. The project focuses on whole genome sequencing for a new approach to rare genetic disorders in the Navarra Health System-Osasunbidea (SNS-O). So far, thanks to collaboration with doctors from 18 medical specialties at the Navarra Hospital Complex (CHN), the study includes data about 400 patients and their relatives, precise diagnoses for 25 per cent patients and identification of possible causes for another 25 per cent.

The patients that are part of the study had not been accurately diagnosed, despite having been treated by several specialists and having taken a large number of traditional tests. Angel Alonso, the coordinator of the project, highlighted the project’s relevance to healthcare services: ‘Making genomic analysis available to the public health system is revolutionary. It means a significant change in the clinical approach to patients with rare genetic disorders.’

Impact on the patient and their family

On the occasion of Rare Disease Day on the last day of February, it is worth mentioning that about 6 per cent of the global population are individuals with rare diseases. In Navarra, their number amounts to 38,000. At present, there are 7000 types of rare diseases, most of them of genetic origin.

In many cases, genetic testing enables the patient and their family to get a deeper knowledge of their condition and its progression, to understand how a genetic disease is inherited and to learn about the risks for other family members. The emotional significance of finding answers to the questions posed by the symptoms – which sometimes have remained unanswered for too long – means putting an end to uncertainty and isolation for most patients with rare diseases.

NAGEN 1000: a pioneering project in Spain

NAGEN 1000 is a ground-breaking project at the national level, placing Navarra at the forefront of genomic analysis and technology. The project was introduced last year at the Senate Presentation of Genomic Studies, whose conclusions were approved in 2019, thus green-lighting the development of a national strategy for personalised medicine.

Currently, the project’s methods, procedures and infrastructure are being transferred to daily clinical practice in SNS-O, to the benefit of the people of Navarra.

NAGEN 1000 is financed by the Economic Development Department at the Directorate-General for Industry, Energy and Innovation within the framework of the Intelligent Specialisation Strategy S3. It is being developed by a consortium made of CHN, Nasertic (a company run by the Government of Navarra), Avantia and Navarrabiomed, leader and coordinator of the project, with the support of the Directorate-General for Information Technology, Telecommunications and Public Information (DIGITIP), and the cooperation of the Centro Nacional de Análisis Genómico (CNAG-CRG) and the Clinical Bioinformatics Research Area into Rare Diseases (CIBERER) of Instituto de Salud Carlos III (ISCIII).

Saioa Mendaza Lainez, investigadora predoctoral en la Unidad de Patología Molecular del Cáncer de Navarrabiomed, realizará la lectura de su tesis doctoral por la Universidad Pública de Navarra el martes 30 de junio, a las 11:30, a través de videoconferencia en Navarrabiomed (solamente podrán acudir aquellas personas autorizadas previamente). 

La tesis, titulada Approaching the epigenome of triple-negative breast cancer to identify new biomarkers, ha sido desarrollada en Navarrabiomed bajo la dirección del Dr. David Guerrero Setas y la Dra. Esperanza Martín Sánchez.

El cáncer de mama es la neoplasia más frecuente en mujeres a nivel mundial y la primera causa de muerte por cáncer en este mismo sexo. La investigación aborda el cáncer de mama triple negativo (CMTN), un subtipo que a diferencia del resto carece de tratamiento dirigido, lo que conlleva consecuencias más agresivas en las personas que lo padecen. Esto hace que a día de hoy, la búsqueda de nuevos biomarcadores y dianas terapéuticas para esta enfermedad sea imprescindible.

Dado que las alteraciones epigenéticas están involucradas en la tumorigénesis, el objetivo de esta tesis ha sido caracterizar la metilación del DNA y la acetilación de histonas de este tipo de cáncer. Con ello se ha buscado identificar nuevas firmas potencialmente diagnósticas y pronósticas, así como alteraciones destinatarias de fármacos dirigidos.

Los resultados de esta caracterización han permitido concluir que el patrón epigenético está alterado en CMTN respecto a tejido mamario no neoplásico. Más importante aún, la investigación ha desvelado dos alteraciones epigenéticas específicas como potenciales biomarcadores de peor pronóstico: la acetilación de la histona H4K5 y la hipometilación del gen ADAM12, el cual se presenta también como posible diana terapéutica frente a este cáncer.

Asimismo, se ha identificado una nueva firma basada en metilación de DNA con utilidad diagnóstica. Por último, se han descrito los procesos biológicos de los distintos genes regulados por la acetilación de H4K6 en líneas celulares no neoplásicas y CMTN.

El trabajo realizado ha dado lugar a tres publicaciones científicas y ha sido difundido en dos congresos consecutivos de European Association for Cancer Research; uno celebrado en Manchester en el año 2017 y en Amsterdam en el 2018.

Para el desarrollo de la tesis Saioa Mendaza ha sido beneficiaria de dos becas: Ayudas para la formación de Personal Investigador de la Univesidad Pública de Navarra  para la realización de tesis doctorales y Beca a la excelencia de la Funcación Caja Navarra para la realización de una estancia en University of Massachussets Medical School (EEUU).

• 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.

•    La asociación y el centro de investigación colaboran desde el año 2014 para el fomento de proyectos de investigación y realización de jornadas de difusión.

Representantes de ANELA Navarra, asociación de pacientes de Esclerosis Lateral Amiotrófica (ELA), acudieron ayer a la sede de Navarrabiomed para reunirse con su directora, Maite Mendioroz, y con la coordinadora del equipo de atención multidisciplinar de ELA del Hospital Universitario de Navarra e investigadora en Navarrabiomed Ivonne Jericó.

Durante el encuentro Montxo Iriarte, presidente de ANELA Navarra, hizo entrega al centro de investigación de un donativo de 20.000 euros, importe recaudado a lo largo del año en varios actos de sensibilización organizados por la asociación.

La financiación recibida se destinará íntegramente al grupo de investigación Enfermedades Neuromusculares y de la Neurona Motora, que lidera Ivonne Jericó y permitirá impulsar la investigación biomédica en ELA y conseguir avanzar en el conocimiento de la enfermedad y la búsqueda de nuevos biomarcadores.

En el año 2014, Navarrabiomed y ANELA Navarra firmaron un convenio de colaboración para el fomento de la investigación en ELA en la Comunidad foral a través de varios proyectos, así como para la promoción conjunta de diversas acciones para visibilizar la enfermedad, sus afectados y sus familias.

Desde entonces, el centro de investigación organiza también de forma periódica jornadas para mantener informados a los y las integrantes de la asociación sobre los avances en investigación que se realizan desde Navarrabiomed y los nuevos tratamientos farmacológicos y ensayos que se están testando a nivel nacional e internacional.