Rare diseases pose one of the greatest challenges for current biomedical research. Their low individual prevalence, clinical heterogeneity, and underlying molecular complexity hinder early diagnosis and limit the development of specific treatments. Although each condition affects a few individuals, their collective impact is considerable: it is estimated that more than 7,000 rare diseases have been described and that, globally, they affect between 6% and 8% of the population, which corresponds to more than 300 million people worldwide.
Against this backdrop, the Sant Pau Research Institute (IR Sant Pau) has made rare disease research a strategic priority. Through its Genomic Medicine and Rare Diseases Program, the center brings together 18 research groups and more than 300 researchers and technical staff. They work in a coordinated manner to improve diagnosis, understand the molecular bases of these conditions, and advance toward more personalized therapeutic approaches. This involves connecting basic research with clinical practice. Since 2018, the program has published more than 2,000 scientific articles and reviews, positioning IR Sant Pau as one of the most active centers in this field.
IR Sant Pau is also the Spanish institution with the greatest representation in the Center for Biomedical Research on Rare Diseases (CIBERER), with five groups funded by the Instituto de Salud Carlos III (ISCIII). This presence reinforces Sant Pau’s role as a leading center in translational research, facilitating the transfer of knowledge from the laboratory to clinical practice.
The center is also fully committed to personalized and precision medicine, an approach that enables treatments to be tailored to patients’ individual genetic characteristics. In this context, it participates in the IMPaCT Project (Infrastructure for Precision Medicine Associated With Science and Technology) through three key initiatives:
Lately, IR Sant Pau has contributed to generating new knowledge in rare diseases with direct implications for diagnosis, clinical standardization, and the understanding of their biological mechanisms. These advances have materialized in both initiatives aimed at unifying care criteria and studies exploring previously underexamined aspects of these conditions.
In this context, the publication of the first European clinical guideline for the management of Alport syndrome has established consensus-based diagnostic and genetic criteria, as well as structured recommendations for patient follow-up. This shared framework facilitates more homogeneous care across Europe and strengthens evidence-based clinical decision-making in this low-prevalence genetic kidney disease.
In the field of multisystem genetic disorders, a study in adults with tuberous sclerosis complex analyzed the burden of untreated neuropsychiatric symptoms in adulthood. The findings highlighted the persistence of unmet clinical needs and underscored the importance of maintaining a comprehensive and continuous approach that integrates neurological, psychiatric, and psychosocial care over time.
Research has also advanced in understanding the pathophysiological mechanisms of certain rare diseases. A scientific review focused on the role of oxytocin in hypopituitarism expanded the perspective on this uncommon endocrine disorder, highlighting potential implications of this neurohormone beyond classic hormonal deficiency and opening new avenues for future clinical research.
In parallel, a review dedicated to primary autoimmune neuropathies delved into the immunological processes involved in these peripheral nervous system disorders, analyzing how the interaction among autoantibodies, immune cells, and neural structures may influence disease progression. This may guide the development of targeted therapeutic strategies.
Finally, the application of advanced magnetic resonance imaging techniques has made it possible to improve the identification of atypical parkinsonisms such as progressive supranuclear palsy and corticobasal degeneration. These rare tauopathies often present overlapping symptoms with more prevalent neurodegenerative diseases, complicating early diagnosis. The incorporation of more precise imaging biomarkers contributes to more objective clinical characterization and the reduction of diagnostic delays.
In addition to the advances already published, IR Sant Pau maintains several active research lines aimed at deepening knowledge of rare diseases and generating new diagnostic and therapeutic opportunities. These initiatives combine basic research, translational approaches, and competitive funding that enables teams to consolidate and dedicate specific time to low-prevalence conditions.
Within this framework, a project focused on Fanconi anemia—a rare hereditary disease characterized by alterations in DNA repair mechanisms and a high predisposition to cancer, particularly oral cancer—analyzes processes of genomic instability associated with the condition and further characterizes genetic variants at a functional level. The goal is to more precisely understand the biological mechanisms involved and their impact on clinical progression. Researchers are currently conducting the first-ever clinical trial aimed at finding a treatment for oral cancer in these patients.
Also in the field of genetic cerebrovascular diseases, the CADASIMUS project is developing a drug repositioning strategy in CADASIL, a rare hereditary cerebral arteriopathy linked to alterations in the NOTCH3 gene. The initiative evaluates already available drugs to determine their potential to intervene in disease-related mechanisms, with the aim of exploring new therapeutic options in a condition that currently lacks specific disease-modifying treatments.
In the diagnostic arena, another ongoing project focuses on the identification and validation of plasma and imaging biomarkers for the diagnosis of 4R tauopathies, a group of uncommon neurodegenerative disorders that includes entities such as progressive supranuclear palsy and corticobasal degeneration. These diseases present significant diagnostic challenges, particularly in early stages, due to symptom overlap with more prevalent conditions. The development of specific biological markers seeks to improve diagnostic precision and objectivity, enabling earlier and more differentiated identification.
Furthermore, a research intensification grant strengthens the line of work focused on amyotrophic lateral sclerosis (ALS), a rare neurodegenerative disease of high clinical complexity. This support allows for greater dedication to clinical and biomolecular research in ALS, consolidating a line aimed at deepening understanding of the mechanisms involved in the disease and advancing its diagnostic and prognostic characterization.
Complementarily, intensification grants also help drive research lines in the field of rare endocrinopathies, in connection with European Reference Networks such as Endo-ERN. This reinforcement of research dedication enables progress in the study of uncommon hormonal disorders and consolidates sustained scientific activity in conditions that require high specialization and continuity to improve their clinical management.
Taken together, these active lines reflect a sustained research strategy that addresses rare diseases at multiple levels—molecular, diagnostic, and therapeutic—allowing for progressive improvements in the precision of their clinical management.
These lines under development, together with the results already achieved, shape a sustained and structured research model that addresses rare diseases from multiple perspectives: clinical, molecular, and technological. The combination of mechanistic studies, advanced diagnostic tools, and translational projects enables progressive advancement toward greater precision in the characterization of these conditions and in the identification of new therapeutic opportunities.
In a field marked by complexity and the low individual prevalence of each disease, progress depends on continuity, specialization, and the ability to integrate diverse knowledge. From this cross-cutting approach, IR Sant Pau contributes to progressively transforming the diagnosis and treatment of rare diseases, aligning research and clinical practice to address a challenge that, while individually uncommon, has a substantial collective impact.
