OTL-203 (Orchard Therapeutics)

OTL-203 is an investigational ex vivo autologous hematopoietic stem cell (HSC) gene therapy developed for the treatment of Mucopolysaccharidosis Type I Hurler variant (MPS-IH). The therapy involves collecting a patient's own CD34+ hematopoietic stem and progenitor cells and genetically modifying them using a lentiviral vector to introduce a functional copy of the human alpha-L-iduronidase (IDUA) gene. Following a conditioning regimen, these modified cells are re-infused into the patient, where they engraft in the bone marrow and differentiate into various lineages, including leukocytes and microglia. These cells then produce and secrete the functional IDUA enzyme, which can be taken up by neighboring cells through a process called cross-correction. This approach aims to provide a sustainable source of the enzyme throughout the body, potentially addressing both the systemic and central nervous system manifestations of MPS-IH by reducing the accumulation of glycosaminoglycans (GAGs).

Other names

idua lentiviral vectorIDUA-LVautologous CD34+ cells transduced with IDUA lentiviral vectorTigetT10_MPSIH