Amarillo (#B88A00)

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).