Enzyme replacement therapy for Sanfilippo A lysosomal rare disease

DESCRIPTION provided by applicant The goal of this SBIR proposal is to develop an effective enzyme replacement therapy ERT for Sanfilippo A patients by exploiting safety supply and cost advantages of plant based enzyme bioproduction while integrating novel ERT delivery strategies being development at BioStrategies LC Sanfilippo A MPS IIIA is a rare genetic lysosomal storage disorder affecting less than people in the U S It is caused by a defect in the gene encoding the enzyme heparan N sulfatase SGSH and is characterized by progressive degeneration in normal childhood development especially in brain function leading to death at an early age Current treatment options are limited to symptom management and development of an effective ERT drug has been hindered by challenges of delivering these drugs to the brain and central nervous system CNS If successful this SBIR will lead to an effective ERT based treatment for Sanfilippo A patients a patient population with desperate need and limited options Utilizing BioStrategiesandapos new plant lectin ERT fusion and delivery technology to be further developed during this project this research could lead to a fundamental paradigm shift for ERT based treatment approaches based on innovative alternate cell targeting mechanisms and trans blood brain barrier BBB drug delivery The promise of plant made bio production to be employed in this project has recently been recognized with the FDA approval of Elelyso Protalix Pfizerandapos s plant made glucocerebrosidase ERT for Gaucher Disease The potential for a marketable product is high With the rare disease community showing escalating interest in reducing drug development and production timelines and costs our new ERT drug technology utilizing plant based bio production will be highly attractive and competitive All Phase I objectives of this SBIR project have been met demonstrating a the feasibility of using plant based bio manufacturing for our complex human gene product and b the ability of our lectin carriers to mediate delivery of active sulfamidase into human cells and lysosomes leading to MPS IIIA disease phenotype correction This Phase II SBIR proposal addresses the following follow on objectives To produce bioactive SGSH lectin fusion drug products at scale and purity to support in vivo mouse model animal trials To evaluate in vivo enzyme distribution in normal and MPS IIIA mice and To assess efficacy in disease correction of our lead drug candidate in the MPS IIIA mouse model Success in Phase II will demonstrate the efficacy of our lectin drug candidate to correct in vivo disease phenotype in the mouse model for this disease supporting subsequent preclinical efficacy and toxicology studies required for a successful IND application to FDA to initiate human clinical trials PUBLIC HEALTH RELEVANCE The family of human genetic diseases represented by Sanfilippo A Syndrome MPS IIIA and other lysosomal disorders LDs include some of the most devastating human afflictions known and the most costly to patients their families and the public health system The currently approved enzyme replacement therapeutics ERTs available to treat several of these diseases although effective for many patients still suffer frm problems of safety high cost availability of adequate product supplies to patient populations and product effectiveness in treating all organs of body The new therapeutics technologies for MPS IIIA developed in this SBIR Phase II Randamp D project would address all of these issues by employing new drug delivery technology that more effectively targets affected cell types cellular compartments and organs The need for delivering new treatment options such as that described in this proposal to the central nervous system CNS and brain is particularly critical as current drug options for LDs are generally not effective in the brain The innovative drug delivery technology developed in this project including our use of cheaper plant based manufacturing would further the national goal of reducing the suffering and costs for patients afflicted with these devastating genetic diseases