Definition

A gene therapy agent composed of a preparation of autologous CD34-enriched hematopoietic stem cells (HSCs) transduced with a lentiviral vector expressing the endogenous human gene alpha-L-iduronidase (IDUA), that may potentially be used in the treatment of mucopolysaccharidosis type I (MPS I; Hurler syndrome). Upon administration, autologous CD34+ enriched IDUA-expressing HSCs OTL-203 express IDUA, which is an enzyme required for the lysosomal degradation of glycosaminoglycans (GAGs). IDUA hydrolyzes the non-reducing terminal alpha-L-iduronic acid residues in GAGs, including dermatan sulfate and heparan sulfate. IDUA deficiency causes accumulations of heparan sulfate and dermatan sulfate in various organs of the body which leads to progressive damage. Mutations in the IDUA gene are responsible for the deficiency of IDUA.