MITO-GARAGE · Deciphering the Roles of the Salvage and De Novo Pathways of Nucleotide’s Metabolism in Mitochondrial DNA Maintenance

Deciphering the Roles of the Salvage and De Novo Pathways of Nucleotide’s Metabolism in Mitochondrial DNA Maintenance

MITO-GARAGE is an ambitious research initiative aimed at addressing the urgent unmet medical needs posed by mitochondrial diseases, with a particular focus on primary Coenzyme Q (CoQ) deficiencies, specifically through pathogenic variants in COQ2, and mitochondrial DNA maintenance disorders (MDDS), specifically through pathogenic variants in GUK1. These rare yet devastating conditions lead to multisystemic involvement, often manifesting with severe neurological, muscular, and metabolic complications, and currently lack effective therapies. The project builds upon a solid foundation of previous research by the two hosts groups at Columbia University (CU) in New York and the University of Granada (UGR), that has identified novel pathogenic variants and mechanistic insights into mitochondrial dysfunction. Through the integration of genetic, biochemical, and cellular approaches, such as studying patient derived fibroblasts and newly generated in vivo models, MITO-GARAGE seeks to deepen the understanding of disease pathology and to evaluate innovative therapeutic strategies. The overall objectives of MITO-GARAGE are threefold: 1. To elucidate the molecular and cellular mechanisms underlying primary CoQ deficiencies and mtDNA maintenance disorders. 2. To develop and test novel therapeutic interventions, including small molecules and formulation improvements, aimed at restoring mitochondrial function. 3. To facilitate the path from bench to bedside through robust preclinical validation, engagement with regulatory pathways, and strategic planning for intellectual property management and potential commercialization. The pathway to impact involves not only the generation of high-quality scientific data but also proactive dissemination to both the scientific community and broader audiences, fostering awareness and paving the way for future clinical trials. By evaluating options such as orphan drug designation, patenting, and possible spin-off creation in collaboration with technology transfer offices (e.g., Columbia Technology Ventures and UGR’s OTRI), MITO-GARAGE aims to maximize the societal and economic benefits of its findings, ultimately improving the quality of life for patients affected by mitochondrial diseases.

Data: CORDIS, © European Union