Rare diseases

• Establish effective and sustained collaborations between research groups with complementary technical, conceptual, and model-system expertise, enabling integrated approaches that would not be achievable within single-group projects. As an initial step, a kick-off meeting will be organized to map ongoing activities, models, and methodologies across participating groups.
• Generate common resources, experimental strategies and frameworks applicable across multiple rare disease models by identifying methodological overlaps. These may include the use of compound libraries, comparative analyses of mitochondrial function (e.g., respirometry), oxidative stress assays, standardized cellular stress markers or shared use of model systems.
• Identify and characterize common pathogenic mechanisms across rare diseases with distinct clinical manifestations, including neurodegenerative disorders and cancer, such as glioblastoma, spinal muscular atrophy, amyotrophic lateral sclerosis, Friedreich's ataxia, and rare genome instability syndromes.
• Facilitate the identification of novel molecular pathways and targets emerging from these mechanistic studies that may inform future preclinical therapeutic strategies and rational drug repurpose efforts.

• Strengthen the institutional positioning of IRBLleida in rare disease research by creating a visible, sustainable and open transversal program that integrates pediatric and adult rare diseases, as well as rare cancers, and that progressively incorporates new groups, clinicians and collaborators as opportunities arise.
• Lay the groundwork for future competitive funding applications, both national and international, through the generation of high-quality preliminary data, the consolidation of collaborative research networks, and the development of interactions with external clinical and scientific communities.
• Enhance training opportunities for early-career researchers, promoting interdisciplinary skills, methodological cross-training, and mobility across research groups participating in the Program.

• Promote social engagement and visibility of rare diseases through coordinated actions with patient associations and relevant stakeholder groups at local, national and international levels, stimulating bidirectional communication between researchers and society.
• Integrate patient perspectives by identifying key needs and concerns through structured interactions with patient associations, using this input to better contextualize biomedical research questions and to guide the design of relevant preclinical research.
• Strengthen the interface between research and emerging rare disease clinical coordination initiatives at HUAV, promoting alignment between experimental research and patient-oriented needs and enabling future translational opportunities.

This line will address Friedreich Ataxia (FA) as a rare cardio-neurodegenerative disease caused by frataxin deficiency.

The focus will be on understanding how altered iron metabolism, redox imbalance, and defects in the mitochondrial electron transport chain contribute to neuronal and cardiac dysfunction.

Studies will integrate neuronal and cardiomyocyte models, patient-derived cell cultures and mouse models to dissect tissue-specific vulnerabilities and identify molecular pathways that could be targeted to restore mitochondrial function and cellular homeostasis.

This line addresses the molecular mechanisms underlying selective neuronal vulnerability in rare neuromuscular disorders, with a particular focus on Spinal Muscular Atrophy (SMA).

Research activities will explore how alterations in SMN-dependent pathways impact motor neuron survival, intracellular homeostasis and stress responses, and how these mechanisms may contribute to disease progression and variable responses to current SMN-targeted therapies.

Neuronal activity and glial cells in the tumor microenvironment fuel tumor growth.

This research line aims to investigate pharmacological and genetic strategies to disrupt the glioblastoma-supportive microenvironment by modulating multiple ion channels expressed both in glioblastoma cells, glial cells (astrocytes and microglia) and neurons.

Each strategy will be evaluated in controlled monoculture systems and in organotypic or defined co-culture models to capture cell-type-specific and interactive effects.

Approaches demonstrating robust efficacy in vitro will be advanced to preclinical validation using murine models of glioblastoma.

This research line focuses on rare inherited syndromes with closely related molecular etiologies, including Fanconi anemia, Bloom syndrome and Atelis syndrome, which are characterized by defects in DNA replication, DNA repair and the maintenance of genome stability.

These disorders will be used as complementary models to dissect fundamental mechanisms of replication stress, chromosomal instability and cellular responses to DNA damage, with the aim of identifying shared vulnerabilities and conserved molecular pathways.

This research line integrates mechanistic studies and clinical translation in amyotrophic lateral sclerosis (ALS) by combining in vitro and preclinical models to dissect molecular and cellular pathways driving motor neuron degeneration and disease progression.

These insights support the development of tailored RNA-based therapies, including antisense oligonucleotides (ASOs), and guide the identification and validation of novel and established biomarkers, such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), to improve patient stratification, treatment monitoring, and clinical management.

This research line will focus on rare forms of diabetes of mitochondrial origin, using them as model systems to investigate how mitochondrial dysfunction contributes to metabolic dysregulation and tissue-specific vulnerability.

The line will address defects in mitochondrial bioenergetics, redox balance, calcium homeostasis and stress signaling pathways that impair insulin secretion and glucose homeostasis.

By integrating cellular models, patient-derived samples and functional assays, this research line aims to identify molecular mechanisms linking mitochondrial impairment to endocrine dysfunction, and to explore shared pathways with other mitochondrial and neurodegenerative rare diseases included in the Program.