The Centre for Biomedical Network Research on Rare Diseases (CIBERER) is a virtual institution composed of 45 basic, clinical and epidemiological research groups distributed throughout 27 different Spanish academic, public research, and university hospital institutions in nine different cities. Formally established in November 2006, over 450 investigators are involved in the effort. The cooperative network aims to establish itself as an international centre of knowledge, transforming the fruits of its research into clinical practice by strongly encouraging collaboration between basic and clinical research. The activities of CIBERER are organised into seven distinct scientific areas that share the common goal of investigating the rare diseases that fall within their respective domains. These areas are: mitochondrial disorders, hereditary metabolic diseases, endocrinal diseases, neurogenetics, congenital and developmental defects, clinical and epidemiology genetics, and genetic instability and cancer predisposition.
CIBERER is led by Scientific Director Dr. Francesc Palau, a specialist in paediatric medicine and medical genetics, working as a senior investigator at the Institute of Biomedicine, Spanish Council of Scientific Research (CSIC) in Valencia. In a recent interview with Redes de Investigacion en Medicamentos, the Spanish pharmaceutical industry publication that featured an in-depth feature article on CIBERER in their July 2007 issue, Dr. Palau described the overall mission of the rare disease scientific network: stimulating and supporting rare disease scientific research, particularly the fields of genetic, molecular, biochemical and cellular investigation.
CIBERER has five principal directives:
Improving the resources available for researching rare diseases and rare disease treatments Promoting the integration between basic and clinical biomedical research groups, in order to unite the laboratory with the clinical setting Developing cooperative investigational projects that permit the exploration of new scientific hypotheses and technological developments Demonstrating the value of rare disease research Establishing collaborative efforts with pharmaceutical and biotechnology firms To achieve these objectives, the CIBERER groups purposely work in intramural settings. Two-thirds of the researchers belong to universities and research institutions, and the rest work from various hospital-based settings, such as genetic clinics. This diversity fosters one of the principal aims of the project: facilitating collaboration between basic and clinical research to create a continuum from the laboratory to the clinical setting, both in terms of diagnostics and treatments. The CIBERER research groups are located all over Spain: Barcelona and Madrid each have 16 research groups and the others are distributed throughout the country: six in Valencia, two in Seville, and one in each of the following five cities: Malaga, Santiago de Compostela, Murcia, La Laguna (Tenerife) and Zaragoza.
CIBERER has its antecedents in the Cooperative Thematic Research networks that were developed in Spain between 2003 and 2006. Of the 69 centres or groups that made up this effort, 11 concerned rare diseases, including the Clinical and Molecular Genetic Centres Network (
RECGEN) and the Research Institute for Genetic-Based Rare Diseases (
INERGEN). CIBERER also collaborates with the Rare Disease Research Institute of the Instituto de Salud Carlos III (
ISCIII), an intramural institute created several years ago that has since been oriented toward epidemiology. CIBERER will work on a project with this group concerning rare disease registries. Determining rare disease prevalence in Spain, particularly for rare genetic-based disorders, is a necessary procedure that can be achieved by creating registries. This task requires close collaboration with hospital and clinical genetic services, as well as patient organisations and other sources. With an estimated 80% of rare diseases having a genetic basis, improving diagnostics in this area is vital. Implementing new technologies that allow automatic large-scale genetic analysis, and ultimately reduce the time to results is also important, and are on the "to do" list amongst CIBERER's many other goals.
CIBERER, created by the ISCIII as a public network structure, is an independent legal entity. Funded by ISCIII, CIBERER has a budget of 6.2 million euros for its first year. This sum is scheduled to increase annually, with a 10% augmentation for the coming year. This monetary commitment reflects the involvement on the part of the government and the general public toward addressing the problem of rare diseases.
CIBERER structures its working scientific areas to maximise cooperative, multidisciplinary research. This intramural approach allows investigators to consider different approaches, exploring new hypotheses and technological developments. Several mechanisms are set up to foster this collaboration. Symposia, in which research between different strategic programmes is shared, are one such device. These seven distinct research areas each has a variety of projects, often working in collaboration with national and international researchers. Each has its own set of working groups and an ambitious agenda of projects geared to forwarding understanding of rare diseases and possible preventive or treatment strategies:
The mitochondrial disorders are multisystemic pathologies that can affect several diverse organs. The scientific coordinator for this area, Pr. Julio Montoya, emphasises the particular significance of mitochondrial disorders to rare diseases. Their multi-systemic character, coupled with an etiology not completely understood, makes working in this field particularly challenging. Yet it is hoped that advances in understanding rare mitochondrial diseases will have repercussions that extend to more common disorders and other branches of medicine. The role of genetics in these illnesses is key and studies employing transmitochondrial cybrids are expected to help decipher the mystery these illnesses present.
The area of hereditary metabolic disorders consists of 12 research groups coordinated by Pr. Magdalena Ugarte. Investigating the molecular foundation of this group of diseases in order to find new therapies is the principal global work objective. Studying defects in cerebral creatine, congenital glycosylation anomalies, cellular physiopathology and new genetic and pharmacological therapy approaches occupies the scientists working in this sector.
The endocrinal disease segment of CIBERER has five research groups that are investigating endocrinal anomalies in rare diseases. Scientific coordinator Dr. Pascual Sanz elaborates in Redes de Investigacion en Medicamento that furthering the understanding of the molecular foundation of genetic endocrinal disorders figures amongst the primary objectives, as well as investigating the epidemiology of genetic or acquired rare endocrinal disorders. The groups in this area have specific and varied objectives, and include the study of the molecular bases of various disorders, such as Lafora-type myoclonic progressive epilepsy, Osler Weber Rendu disease, or those caused by mutations in the human pancreatic gluco-kinase or AMP kinase gene. Analysing the genes involved in sex differentiation, congenital hyperthyroidism, and the morbidity-mortality of Cushing syndrome and acromegalia are other topics under investigation. This group is also responsible for the coordination, development and launch of the European Registry on Cushing syndrome (ERCUSYN) and the Spanish Acromegalia registry.
The neurogenetics group, coordinated by Dr. Montserrat Baiget, has the global objective of furthering understanding of the causes and mechanisms of rare neurogenetic pathologies in order to ultimately develop new diagnostics and therapies. Five research groups throughout the country are working on a variety of projects. Major disorders addressed include muscular dystrophies, spinal muscular atrophy, Charcot-Marie-Tooth disease, Friedreich ataxia, retinal dystrophies and genetic deafness.
The congenital and developmental defects research sector of CIBERER is coordinated by Dr. Carmen Ayuso. These disorders affect as many as 5% of newborns, and lead to elevated morbidity and mortality rates, especially in developing countries. This research sector consists of five working groups, one of which is devoted to epidemiology. Projects include studying the embryology of the vertebrae and disorders related to bone development, analysing genetically modified mice models of diseases such as Wiskott-Aldrich syndrome and other chromosomal pathologies. Other projects concern hereditary ocular pathologies (with participation in Spanish project EsRetNet and European FP6 project Evi Genoret), non-invasive prenatal diagnostics, the identification of chromosomal and genetic causes of infertility, and the study of congenital malformations such as bone dysplasias.
The clinical and epidemiology genetics work package is coordinated by Dr. Guillermo Antinolo, and is focused on better harnessing the numerous advances in the field of genetics that are allowing for deeper understanding of many rare diseases and how they are transmitted. Prenatal diagnosis and reproductive genetics is one topic of study, along with work being conducted to analyse the molecular basis of several rare disorders, including Hirschsprung disease, and hereditary cancers. Population genetics is being investigated, and the work area has multi-disciplinary research teams consisting of biologists, physicians, psychologists, statisticians, and laboratory workers collaborating to characterise rare diseases and accomplish related tasks.
Genetic instability and cancer predisposition is the seventh research area of CIBERER. The six working groups, coordinated by Pr. Jordi Suralles, are investigating mutations leading to genomic instability. Diseases such as Fanconi Anaemia, which has 13 genes implicated to date, and hereditary cancer are the focus of research for this working group. One research group is focusing on bioinformatics, while another is working on gene therapy for skin disorders such as epidermolisis bullosa.
At the first annual meeting of CIBERER, taking place in November, scientists from the seven main disciplines of research will be able to share the fruits of their efforts.
Though less than a year old, the CIBERER research groups are remarkably active, producing research and publishing their findings. To date, almost 20 publications written by or in collaboration with various CIBERER research groups can be found on PubMed and 35 publications and meeting reports can be found in the ISI Thompson Web of Science. This research includes studies in fundamental and clinical science and can be found in some of the leading international scientific and medical journals.
CIBERER stands as a model of innovation and commitment in the field of rare disease research, whose efforts seem poised to benefit rare disease patients and their families not only in Spain, but all over Europe and the world.
