Lectin-mediated ERT Delivered to Cardiac Tissue in Fabry Disease

The current inability to effectively deliver corrective doses of lysosomal enzymes to key cells involved in cardiovascular and cerebrovascular disease remains a significant hurdle for rare lysosomal disordersLSDsuch as Fabry disease and other diseases with significant cardiovascular pathologiesBioStrategies LC is developing the plant lectin RTB as a carrier capable of expanding enzyme delivery tohard to treatorgans and tissues including heartbrainand boneLectin mediated ERT delivery has recently shown promise in other LSDs including MPS I and GMThis SBIR is focused on developing adelivery enhancedenzyme replacement therapyERTfor patients with Fabry diseaseFabry is a X linked LSD caused by genetic deficiencies in alphagalactosidase AGalAleading to severe multi organ pathologies with cardiac deathfollowed by strokeas the leading causes of deathFabry disease has emerged as the key LSD model for heart disease due to extensive cardiomyopathy and other cardiovascular presentationsOur long term goal is to bring an ERT capable of treating the full spectrum of progressive cardiac and other disease manifestations to Fabry patientsObjectives of this Phase I SBIR feasibility study are to produce bioactiveGalA RTB fusions and demonstrate product delivery into human myocytescorrection of lysosomal phenotype in Fabry cellsand biodistribution to heart and other tissues in the Fabry mouse modelSuccess in Phase I feasibility goals will support moving on to rigorous Phase II SBIR follow up preclinical assessments aimed at moving this promising ERT product to an INDThe feasibility established here will also support expanding the RTB carrier system to other ERTs and therapeutics for diseases having life threatening cardiovascular involvement NARRATIVEPUBLIC HEALTH RELEVANCEThe family of human genetic diseases represented by Fabry Syndrome and other rare lysosomal disorders include some of the most devastating human afflictions known and the most costly to patientstheir familiesand the public health systemThis project addresses the need for delivering enzyme replacement therapeuticsERTdrugs to cardiac tissuesa problem that currently available ERT drugs for this disease do not address and Fabry disease is particularly appropriate for this project because carriers of this genetic defect often suffer from Fabry related cardiac problems as the leading cause of deathThe innovative RTB ERT drug delivery technology developed in this project would further the US national goal of reducing heart disease in general and the suffering and costs for patients afflicted more specifically with Fabry and other genetic and metabolic diseases which affect normal cardiac development