An international study published in the prestigious scientific journal Cell identifies a potential therapy for Leigh syndrome, a severe pediatric mitochondrial disease that until now has lacked effective treatments. The work includes a fundamental contribution from Avantea in the development of the animal model used to validate the treatment.
The research, coordinated by the Universities of Düsseldorf, the University of Milan, and the University of Verona, with the involvement of the Carlo Besta Neurological Institute and Avantea, identified sildenafil, a drug already approved for clinical use, as a promising candidate for the treatment of Leigh syndrome.
The study adopted a translational pharmacology approach, starting from patient-derived induced pluripotent stem cells (iPSCs), from which diseased neuronal cells were generated. These cellular models were used to perform a high-throughput screening of more than 5,600 repurposable drugs, leading to the identification of sildenafil as a molecule capable of improving cellular energy metabolism and function.
A crucial step of the research was the in vivo validation of the results, made possible thanks to the SURF1-KO porcine model of Leigh syndrome developed by Avantea in collaboration with the group of the Carlo Besta Neurological Institute led by Dr. Dario Brunetti. The animal model, previously described in the scientific literature, was generated by the Avantea team composed of Roberto Duchi, Maria Barandalla, Marco Scaglia, Andrea Perota, and Cesare Galli.
In the animal models, treatment with sildenafil demonstrated the ability to improve the disease phenotype and significantly prolong survival, confirming the results obtained in cellular models and paving the way for possible clinical applications.
This result highlights the value of the advanced animal models developed by Avantea as essential tools for translational biomedical research. The ability to study human genetic diseases in highly representative animal models enables the validation of new therapeutic strategies and accelerates the transition from laboratory discovery to clinical testing, contributing to the development of innovative treatments for rare diseases that currently lack effective therapies.
The ability to study and treat human genetic diseases in highly representative animal models such as the pig will help reduce the currently very high failure rate of clinical trials (88–90%), significantly lowering costs and, most importantly, enabling faster clinical validation of the selected drug.
🔬 Published in Cell
Zink et al., Pluripotent stem cell-based drug discovery uncovers sildenafil as a treatment for mitochondrial disease (2026) https://www.sciencedirect.com/science/article/pii/S009286742600173X