Treatment of muscular symptoms in Pompe rare disease via lectin assisted ERT delivery

The current inability to effectively deliver corrective doses of lysosomal enzymes to key cells involved in muscular disease symptoms remains a significant hurdle for rare lysosomal disorders (LSD) such as Pompe disease and other similar diseases with significant muscular-skeletal pathologies. BioStrategies LC is developing the plant lectin RTB as a carrier capable of expanding enzyme delivery to “hard-to-treat” organs and tissues including the brain, heart, and skeletal muscle tissues. Lectin-mediated ERT delivery has recently shown promise in other LSDs including MPS I and GM1. This SBIR is focused on developing a “delivery-enhanced” enzyme replacement therapy (ERT) for patients with Pompe disease. Pompe is an autosomal recessive LSD caused by genetic deficiencies in acid alpha-glucosidase (GAA) leading to progressive multi-organ pathologies particularly focused on severe symptoms in smooth, cardiac and skeletal muscles. Pompe disease in its severe forms can lead to death due to extensive cardiomyopathy and respiratory muscle failure.Our long-term goal in this research project is to bring an ERT capable of treating the full spectrum of progressive muscular and other disease manifestations to Pompe patients. Objectives of this Phase I SBIR feasibility study are to produce bioactive GAA:RTB fusions and demonstrate ERT product delivery into human myocytes, correction of lysosomal phenotype in Pompe cells, and biodistribution to skeletal muscle, heart, and other tissues in the Pompe mouse model. Success 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 IND. The feasibility established here will also support expanding the RTB carrier system to additional ERT drugs and therapeutics for other diseases having life-threatening muscle pathologies.NARRATIVE – PUBLIC HEALTH RELEVANCE: The family of human genetic diseases represented by Pompe Disease and other rare lysosomal disorders include some of the most devastating human afflictions known and the most costly to patients, their families, and the public health system. This project addresses the need for delivering enzyme replacement therapeutics (ERT) drugs to muscle tissues in particular, a problem that currently available ERT drugs for this disease do not address adequately. The innovative lectin (RTB)-ERT drug delivery technology developed in this project would further the US national goal of reducing muscular-skeletal diseases in general but more particularly the suffering and costs for patients afflicted with Pompe and other rare genetic and metabolic diseases which affect normal muscle development.