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.
