AGT‑181 is a novel, investigational enzyme replacement therapy (ERT) for the treatment of neurological complications in patients with Hurler syndrome. AGT-181 takes advantage of the body’s natural system for transporting products across the blood-brain barrier (BBB) by targeting the same receptor that delivers insulin to the brain. Its ability to cross the BBB makes it unique among treatments for Hurler syndrome.
ArmaGen developed AGT-181 by re-engineering an enzyme called iduronidase (IDUA) as an immunoglobulin G (IgG) fusion protein. The fusion protein binds to insulin receptors located on the surface of the BBB, enabling its passage into the brain.1, 2 Pre-clinical studies with AGT-m181 desmonstrated reversal of lysosomal storage in brain of a mouse model of adult MPS-I.3
AGT-181 is currently being studied in a Phase 2 proof of concept clinical trial in pediatric patients.
ArmaGen CEO Mathias Schmidt describes the data from the AGT-181 Phase 1/2 study and explains what it could mean for Hurler syndrome and other lysosomal storage diseases.
1 Boado RJ, Zhang Y, Zhang Y, Xia CF, Wang Y, Pardridge WM (2008) Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier. Biotechnol Bioeng. 99:475-84
2 Boado RJ, Pardridge WM (2017) Brain and Organ Uptake in the Rhesus Monkey in Vivo of Recombinant Iduronidase Compared to an Insulin Receptor Antibody-Iduronidase Fusion Protein. Mol Pharm. 14:1271-7
3 Boado RJ, Hui EK, Lu JZ, Zhou QH, Pardridge WM (2011) Reversal of Lysosomal Storage in Brain of Adult MPS-I Mice with Intravenous Trojan Horse-Iduronidase Fusion Protein. Mol Pharm. 8:1342-50