OTL-204

OTL-204 is an investigational ex vivo autologous hematopoietic stem cell (HSC) gene therapy being developed for the treatment of frontotemporal dementia caused by mutations in the progranulin gene (GRN-FTD). The therapy involves collecting a patient's own HSCs and genetically modifying them using a lentiviral vector to introduce a functional copy of the human GRN gene. These modified HSCs are then re-infused into the patient, where they are expected to engraft in the bone marrow and differentiate into various cell types, including microglia that migrate to the central nervous system (CNS). Once in the brain, these cells secrete progranulin, potentially restoring levels of the protein and addressing the underlying cause of neurodegeneration and neuroinflammation in GRN-FTD. The program was developed by Orchard Therapeutics (now a subsidiary of Kyowa Kirin) in collaboration with Boston Children's Hospital and the University of Padua.