Enzyme replacement therapy for Sanfilippo A lysosomal rare disease

点击翻译按钮获取中文摘要

 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 200,000 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 BioStrategies' 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/Pfizer'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: 1) To produce bioactive SGSH:lectin fusion drug products at scale and purity to support in vivo mouse model animal trials, 2) To evaluate in vivo enzyme distribution in normal and MPS-IIIA mice, and 3) 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.