AVROBIO Expands Lentiviral Gene Therapy Pipeline with Program for Hunter Syndrome - Seite 3

About Hunter syndrome

Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), is a lysosomal disorder caused by a mutation in the IDS gene that leads to a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS), which is essential for breaking down large sugar molecules called glycosaminoglycans (GAGs, also known as mucopolysaccharides). Without functional IDS, toxic levels of GAGs build up throughout the body and central nervous system, causing a wide range of symptoms including cognitive decline and cardiac and respiratory dysfunction. The current standard of care is weekly enzyme replacement therapy, which may delay some symptoms but does not halt the overall progression of disease and does not cross the blood-brain barrier, an intricate web of protective tissue that selectively prevents macromolecules from entering the brain. Even with treatment, people with Hunter syndrome face life-limiting symptoms and a significantly reduced life span. The disorder affects an estimated one in 100,000 to one in 170,000 males worldwide; about two-thirds of cases have an early, severe progressive form.

About AVROBIO’s personalized gene therapy approach

Our investigational lentiviral gene therapies start with the patient’s own hematopoietic stem cells. We use a lentiviral vector to transduce those cells in order to insert a therapeutic gene designed to enable the patient to produce a supply of the functional protein they lack. These cells are then infused back into the patient, where they are expected to engraft in the bone marrow and produce generations of daughter cells, each containing a copy or copies of the therapeutic gene. To optimize engraftment, we use a personalized conditioning regimen with precision dosing of busulfan to make space and enable durable engraftment in the patient’s bone marrow and central nervous system (CNS). Busulfan is an established conditioning agent that has been administered to hundreds of patients treated with lentiviral gene therapies. Our approach is designed to drive durable production of the functional protein throughout the patient’s body, thereby potentially addressing symptoms from “head to toe,” including those originating in the CNS.