Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich's ataxia models - PubMed
3 days ago
- #Friedreich's ataxia
- #cell-penetrating peptide
- #hematopoietic stem cells
- The study developed a fusion protein containing secretion and cell-penetrating sequences fused to frataxin to treat Friedreich's ataxia (FRDA), a neurodegenerative disease caused by reduced frataxin levels.
- In vitro experiments showed the protein could be secreted, penetrate cells, localize to mitochondria, and rescue biochemical defects and apoptosis in FRDA patient cells.
- Hematopoietic stem and progenitor cells (HSPCs) from FRDA model mice were transduced with a lentiviral vector carrying the therapeutic cDNA and transplanted, leading to stable peptide secretion in blood and delayed symptom onset.
- Patient-derived CD34+ HSPCs transduced with the vector differentiated normally into macrophages and secreted the peptide, supporting a cell and gene therapy strategy for long-term FRDA stabilization.