- The CSIC launches a Rare Diseases Network to foster collaboration among scientists researching some of the over 7,000 low-prevalence conditions that affect three million people in Spain
Collaboration between hospitals and research centers in the field of rare diseases (RDs) now has a new initiative to boost research into more than 7,000 rare pathologies, which together affect approximately 300 million people worldwide and three million in Spain. This initiative is the creation of the CSIC Rare Diseases Network (RER-CSIC), the first CSIC researchers’ network dedicated to the study of these conditions. The RER-CSIC has been funded through a Special Intramural Project (PIE) from the CSIC and currently brings together 120 research groups from CSIC centers across Spain.
The director of the Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), Pilar López Larrubia, is the principal investigator of the PIE and one of the two coordinators of the RER-CSIC. Through this initiative, López Larrubia aims to strengthen the IIBM, along with a large number of scientists, as leading references in RD research—an important yet often neglected area of medicine. The IIBM has long had a Department of Rare Diseases, which includes seven research groups that study the genetic causes and molecular mechanisms of several low-prevalence diseases in order to improve diagnosis and promote the development of new therapies. The IIBM stands out for being the only CSIC center with a dedicated RD department.
Both Pilar López Larrubia and the network’s second coordinator, researcher Pascual Sanz from the Instituto de Biomedicina de Valencia will drive forward the multidisciplinary understanding and approach to these conditions, addressing society’s growing concern regarding the care needed for people living with rare diseases. The RER-CSIC will enhance the diagnosis and treatment possibilities for individuals affected by RDs. Moreover, it will contribute to a deeper understanding of the cellular mechanisms that govern human biology, shedding light on essential biomolecular processes in health and disease.
López Larrubia acknowledges that the complexity and heterogeneity of RDs present enormous challenges that require collaborative efforts: “The broad experience, interdisciplinary focus, and scientific excellence of CSIC research groups give this institution the potential to make a significant impact on the understanding and therapeutic approach to rare diseases in Spain—an effort that must be matched with increased funding,” she concludes.
To celebrate the establishment of the RER-CSIC, the network’s first meeting will take place on October 28–29, 2024, in the Gabriella Morrealle Auditorium at the IIBM. The event will be opened by Isabel Varela (Advisor to the Presidency of the CSIC), representing Eloísa del Pino, and will bring together most of the expert RD researchers already part of the RER-CSIC to share scientific strategies and technologies that can advance the pathophysiological understanding of rare diseases.
Isabel Varela (advisory board of the CSIC Presidency). Biomedicine Plan
The challenge of diagnosing a rare disease
The more than 7,000 known rare diseases are defined by their low prevalence: they affect fewer than 50 people per 100,000. Of the 300 million people worldwide living with these conditions—about 6–8% of the global population—three million live in Spain. Within the broad RD category lies a subcategory of “ultra-rare” diseases, which affect fewer than one person per million, yet still represent a significant global burden.
The most immediate benefit of researching the genetic basis of RDs, according to Víctor Luis Ruiz Pérez—current director of the IIBM’s Department of Rare Diseases—is the ability to provide a diagnosis to families who otherwise lack answers. For him, basic and clinical science must go hand in hand: “I’ve always been drawn to research that aims to end the uncertainty for families who don’t know the cause of a loved one’s disease.”
Ruiz Pérez, an expert in the genetics and pathophysiology of RDs, exemplifies the synergy between clinicians and basic researchers: “Our research often helps physicians provide an accurate genetic diagnosis to patients with rare conditions. We search for the cause of the disease—either by identifying new disease-causing genes or by determining whether a genetic variant in a previously associated gene is indeed pathogenic,” he explains.
The RER-CSIC has clear goals that are shared across all rare diseases: to achieve early diagnosis for patients, to expand pathophysiological knowledge, and to develop treatments that alleviate or cure the condition. “We must do research to improve patients' quality of life. This is a fundamental duty. But we also want to highlight the value of basic research, because the biological insights gained from studying the molecular mechanisms of RDs can also be applied to more prevalent diseases—making the impact even greater,” argues Ruiz Pérez.
Early diagnosis is vital for rare diseases, as it enables timely preventive measures to be taken. This is also emphasized by the Federación Española de Enfermedades Raras (FEDER), which currently lists 3,069 rare pathologies in Spain. Today, molecular diagnosis of RD patients is mainly carried out using next-generation sequencing, either through whole-genome sequencing or targeted gene panels. This methodology has revolutionized RD research by facilitating the discovery of new genetic variants. However, “sometimes a rare variant is found in a candidate gene, but its significance is uncertain, meaning we can’t confirm if it's the cause of the disease in that patient. In such cases, we must perform further analyses, such as screening other potential candidate genes,” concludes Ruiz Pérez.
Photo of the researcher Sandra Franco Caspueñas from the Department of Rare Diseases of the IIBM
Conserved genes in the evolutionary history of life
Basic science helps elucidate the pathophysiological mechanisms of disease, paving the way for diagnosis and the design of new treatments. The research team led by Dr. Ricardo Escalante at the IIBM—one of the groups in the RER-CSIC—studies a molecular mechanism essential for proper cell function that is altered in certain RDs: autophagy.
“Autophagy is an intracellular degradation process that allows cells to dispose of damaged proteins and organelles. It is essential for cellular health,” explains Escalante. His group uses basic science to study several RDs through simple experimental models. While mice and zebrafish are widely used model organisms, basic RD research is also conducted in simpler eukaryotes like yeast (Saccharomyces cerevisiae) or amoebae (Dictyostelium discoideum). “These models are extremely useful in the lab because they allow us to simplify processes that also occur in humans,” Escalante explains.
The scientific value of these model organisms in RD research lies in the fact that some rare diseases are caused by mutations in genes that are highly conserved throughout the evolutionary history of life. “In some cases, a mutation that causes a disease in humans also affects an amoeba, because the molecular pathways involved are similar and have been preserved for millions of years,” he illustrates. However, Escalante adds, “while these models help us understand fundamental aspects of cell function, more complex models like mice are still necessary—especially when it comes to testing potential therapies.”
The interaction between CSIC research groups—whether focused on basic science, technology, or social perspectives—is key to improving the diagnosis and treatment of patients with rare conditions.
Cover photo: Isabel Varela, Pilar López Larrubia, Pascual Sanz, Pura Fernández and Jordi Pérez Tur