Pre-clinical assessment of protein replacement therapy in the central nervous system of Friedreich’s ataxia mouse models

This project explores a novel approach: attaching mature frataxin to small shuttle peptides that help it cross the blood-brain barrier (BBB), the protective barrier that separates the bloodstream and the brain. After screening several candidates, Dr. Navarro and her collaborators identified a promising shuttle peptide for delivering frataxin to the central nervous system (CNS). The study will first test the safety and biodistribution of this frataxin-peptide conjugate in healthy mice. Then, two FA mouse models will be treated to evaluate whether this strategy improves neurological and pathological features compared to frataxin alone or another shuttle peptide currently in clinical trials. If successful, this approach could overcome a major barrier in FA therapy by enabling effective protein replacement in the brain, offering hope for treatments that prevent or reverse CNS damage.