Protein therapeutics can be re-engineer as brain penetrating IgG-fusion proteins for the CNS treatment of rare disorders, like Lysosomal Storage Disorders (LSD). Lysosomal enzymes, such as iduronase (IDUA) and sulfatases, are large molecule drugs that do not cross the blood-brain barrier (BBB). The BBB-penetration of enzyme therapeutics is enabled by re-engineering the recombinant enzyme as bi-functional IgG fusion proteins, wherein the IgG domain targets a specific endogenous receptor-mediated transporter system within the BBB, such as the human insulin receptor (HIR). The enzyme therapeutic domain of the fusion protein exerts the pharmacological effect in brain once across the BBB. Several brain penetrating IgG-fusion proteins have been engineered and validated. First in human proof of concept phase II clinical trial in LSD will be discussed.
Note that this is scheduled for oral presentation in the Scientific Session 2: Drug Delivery, Wednesday September 26, 2018, 9:30-12:30. Thanks