Improving MPS I ERT Efficacy through Lectin-Mediated Delivery

The long term goal of this project is to develop an improved ERT for MPS I patients with innovations that enhance ERT delivery and disease correction in hard to treat organs such as the brain while integrating safety and cost advantages of plant based bioproductionMPS I Syndrome is caused by genetic deficiencies in the lysosomal enzymeL iduronidaseIDUAWhile current ERT drug options for MPS I effectively treat many visceral organssignificant debilitating manifestations of this disease in the central nervous systemCNSremain to be addressedPrevious cellular studies by BioStrategies showed that this lectinwhich has high affinity for glycoproteins and glycolipids common on mammalian cell surfacescan mediate efficient cellular uptaketranscytosisand delivery of IDUA to lysosomesIn vitro analyses of MPS I patient fibroblasts treated with our IDUA Lectin fusiontermed IDUALdemonstrated rapid and efficient correction of cellular disease phenotypesOur Phase I feasibility animal studies on this project have shown that IDUAL could be delivered to the brains of MPS I mouse model animals yielding correction of both cellular and behavioral phenotypes of this disease and achieving the milestone objectives of the Phase I studySpecific aims for this follow up Phase II proposal areAssess in vivo drug dosage levelsfrequencyand CNS drug delivery and efficacy readouts in MPS I miceDevelop IDUAL product scale upstabilityand qualification protocols to support advanced preclinical studiesandEstablish rigorous preclinical animal data assessing efficacyage at treatment onsetimmunogenicitygender effectsand behavioral correction following long term IDUAL administrationAchievement of phase I goals of this project showing in vivo cellular and behavioral animal efficacy of IDUAL has provided a critical proof of concept for our lectin carrier ERT fusion drug delivery technologyThe overall goal of this Phase II renewal project will be to complete the next stage of drug production scale upand highly rigorous animal studies that will lay a solid foundation for the follow up preclinical research that will be required to support a successful IND application for initiating clinical trailsFurtherance of our successful proof of concept studies on this project will build a solid basis for potential applications of this lectin based drug delivery technology platform to a wide variety of other previously hard to treat diseases