Ruben, ArmaGen, Inc.
Brain Penetrating IgG Fusion Proteins: from Genetic Engineering to Clinical Trials in Lysosomal Storage Disorders
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.
Dr. Boado co-founded ArmaGen in 2004, following more than 25 years of academic experience in fields of molecular and cell biology of the blood-brain barrier, and drug delivery to the brain. His leadership and expertise have been instrumental in the development of ArmaGen's extensive product pipeline, including potential biotherapeutic treatments for mucopolysaccharidosis, stroke, Alzheimer's disease and Parkinson's disease. Dr. Boado was the principal investigator in a number of Small Business Innovation Research (SBIR) programs granted by the National Institutes of Health to ArmaGen. Dr. Boado is also a co-inventor of the intellectual property that supports ArmaGen's pipeline. He is Professor Emeritus of Medicine at UCLA, and has published over 200 scientific peer-reviewed publications and book chapters in his research field.