Enzyme replacement therapy for GM1 gangliosidosis lysosomal rare disease

The goal of this SBIR proposal is to develop an effective enzyme replacement therapyERTfor patients suffering from GMGangliosidosis by applying a novel ERT enzyme lectin fusion delivery strategy developed at BioStrategies LC and by exploiting safetysupplyand cost advantages of a plant based ERT protein bio manufacturing systemGMGangliosidosis is a rare lysosomal disease affecting less thanpeople in the U SIt is caused by a defect in the gene encoding the enzymegalactosidase and is characterized by progressive degeneration of normal childhood development especially in brain function leading to death at an early ageCurrent treatment options are limited to management of disease symptoms and development of an effective ERT drug has been hindered by challenges of delivering these drugs across the blood brain barrier to the brain and central nervous systemThis research project is a collaboration between BioStrategies LCa company focused on doing innovative research in lysosomal disease ERT developmentand StJude Children s Research Hospitalan international center for GMGangliosidosis researchThis SBIR Phase II is designed to lead to an effective ERT treatment for GMGangliosidosis patientsa patient population with desperate need for new therapeutic optionsIn Phase I we met project goals by showing that a plant produced ERT consisting of a fusion between humangal and the plant RTB lectin could be delivered into lysosomes of human disease cells where it reduced the pathogenic levels of GMsubstrate to normalFollow up animal studies in the GMdisease mouse model showed that this ERT complex was effective in delivering active enzyme to tissues of both visceral organs and the CNS producing a significant reduction in the high levels of GMenzyme substrate associated with the GMdisease phenotypeThese results raise the hope that this novel plant lectin ERT fusion cell delivery technology could lead to a general paradigm shift for ERT based treatment approaches in which ERTs could be used to effectively treat diseases that significantly affect the central nervous systemBased on our successful Phase I outcomesPhase II will focus on detailed analyses confirming disease correction within the CNS and visceral organs of GMgangliosidosis miceproduct scale up and characterization to support further preclinical assessments and follow on long term animal studies on pharmacodynamicsdosing administration parametersand amelioration of disease manifestations with larger cohort sizes and gender representation consistent with Rigor and Reproducibility guidanceThese studies will support our goal of gaining sufficient data to support a successful application to FDA for IND approval